Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\n
Throughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
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In this new context of variability and climatic changes, these ecosystems undergo notable modifications amplified by domestic uses of which it was subjected to. Indeed the ecosystems render diverse services to humanity from their composition and structure but the tolerable levels are unknown. The preservation of these ecosystemic services needs a clear understanding of their complexity. The role of research is not only to characterise the ecosystems but also to clearly define the tolerable usage levels. Their characterisation proves to be important not only for the local populations that use it but also for the conservation of biodiversity. Hence, the measurement, management and protection of ecosystems need innovative and diverse methods. For all these reasons, the aim of this book is to bring out a general view on the function of ecosystems, modelling, sampling strategies, invading species, the response of organisms to modifications, the carbon dynamics, the mathematical models and theories that can be applied in diverse conditions.",isbn:null,printIsbn:"978-953-51-0572-5",pdfIsbn:"978-953-51-5289-7",doi:"10.5772/2276",price:139,priceEur:155,priceUsd:179,slug:"diversity-of-ecosystems",numberOfPages:498,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"ee698d03ccce547bc8cdb4f13ebb2822",bookSignature:"Mahamane Ali",publishedDate:"April 27th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/1850.jpg",numberOfDownloads:46825,numberOfWosCitations:74,numberOfCrossrefCitations:22,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:86,numberOfDimensionsCitationsByBook:2,hasAltmetrics:0,numberOfTotalCitations:182,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 10th 2011",dateEndSecondStepPublish:"June 7th 2011",dateEndThirdStepPublish:"October 12th 2011",dateEndFourthStepPublish:"November 11th 2011",dateEndFifthStepPublish:"March 10th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"103960",title:"Prof.",name:"Mahamane",middleName:null,surname:"Ali",slug:"mahamane-ali",fullName:"Mahamane Ali",profilePictureURL:"https://mts.intechopen.com/storage/users/103960/images/system/103960.jpg",biography:"Prof. Ali Mahamane is a Lecturer at Abdou Moumouni University (Niger). He was born in 1964 at Kendadji, Tillabéri, Niger. He got his first degree in Agricultural Sciences from the Abdou Moumouni University and later specialised in Arid Regions Forestry (ENGREF, Montpellier, France). He pursued his studies at the University of Ouagadougou, Burkina Faso where he obtained his M. Phil in 1997. In 2000, he got a tenure appointment at the Faculty of Sciences at Abdou Moumouni University. He registered for his Ph. D thesis at the Université Libre de Bruxelles, Belgium in April 2005. He published more than 38 Scientifics articles both in national and international journals. He is National Coordinator of UNDESERT Project (Understanding and combating desertification to mitigate its impact on ecosystem services). \nPresently Ali Mahamane is Deputy Vice Chancellor and Dean of Faculty of Sciences and Technics at the University of Maradi (Niger).",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Abdou Moumouni University",institutionURL:null,country:{name:"Niger"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"841",title:"Biodiversity",slug:"environmental-sciences-ecology-biodiversity"}],chapters:[{id:"36220",title:"Macrofaunistic Diversity in Vallisneria americana Michx. in a Tropical Wetland, Southern Gulf of Mexico",doi:"10.5772/35331",slug:"macrofaunistic-diversity-in-vallisneria-americana-michx-in-a-tropical-wetland-southern-gulf-of-mex",totalDownloads:2486,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:null,signatures:"Alberto J. 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1. Introduction
Despite considerable progress in detoxification, pharmacology, and psychological interventions in addictive behaviors, clinical outcomes remain suboptimal (e.g., high relapse rate or poor quality of life) [1]. The main reason of the poor clinical outcomes is likely to be related to multiple interacting determinants of social, psychological, and biological mechanisms involved in the addiction risk and the relapse, a view that is not compatible with pure essentialism and simplistic approaches of addiction [2].
Inter-individual variations within the addiction group in respect to neurobiological mechanisms of addiction were highlighted by influential theorizations [3, 4, 5, 6, 7, 8, 9]. Indeed, addictive behaviors can be viewed as the product of an imbalance between separate, but interacting, neural systems: an impulsive, largely amygdala-striatum-dependent, neural system that promotes automatic, habitual, and salient behaviors; a reflective, mainly prefrontal cortex-dependent, neural system for decision-making, forecasting the future consequences of a behavior, and inhibitory control; and the insula that integrates interoception states into conscious feelings and decision-making processes that are involved in uncertain risk and reward. Any imbalance in the dynamics of these systems can account for poor decision-making (i.e., prioritizing short-term consequences of a decisional option), and the lack of willpower [10, 11, 12], which heightens the risk for addiction and relapse.
As part of the “executive network” involving ventrolateral prefrontal cortex and dorsolateral prefrontal cortex, response inhibition interacts with automatic behavioral (“habit network”) and motivational responses (“reward network”) to produce flexible actions and adaptive choices. Indeed, the inhibition of a prepotent response has become an important element of the responsible braking system and limiting the expression of spontaneous motivation and emotion signals [13]. Indeed, successful self-regulation requires the ability to inhibit impulses that are not compatible with one’s goals [14].
Importantly, psychostimulant dependence, alcohol dependence, and gambling disorders have been consistently associated with a response inhibition deficit [5]. However, the deficit in inhibition observed in addiction population is generally of low or moderate effect size [15, 16]. Nevertheless, even a small effect size can have clinically relevant effects, as evidenced by the impact of impaired response inhibition on the risk of dependence and response to treatment [9, 17, 18, 19]. Indeed, response inhibition is considered as a primary candidate for cognitive remediation that can potentially reduce the risk of addiction and the relapse [20]. As an alternative way consistent with dual-process theories, to limit these risks is to reduce the need for inhibitory control, for instance, by dampening automatic conditioned responses (e.g., craving, attentional and memory biases) triggered by contextual (e.g., the sight of a bottle of beer) or internal (e.g., negative effects) cues. In addition, more automatic forms of response inhibition could be trained in the hope of enabling individuals to generate appropriate alcohol-stop associations without too much of an effortful process [21].
In this chapter, we investigate the manner the risk associated with too limited response inhibition can be reduced by implementing multiple forms of cognitive training, invasive and noninvasive brain stimulation techniques, and neurofeedback (NF). It should be noted that an overwhelming majority of neuroscientists engaged in brain stimulation in psychopathology has truly viewed brain-based interventions as complementary interventions to clinical treatments such as cognitive-behavioral therapy and motivational enhancement intervention [22, 23]. Indeed, the beliefs, desires, emotions, and intentions of patients are essential elements to take into account [2], which can be modulated by brain- and cognitive-based interventions.
After a brief presentation of response inhibition theories and methods, we summarize cognitive training intervention in the context of addictive behaviors as well as three brain stimulation techniques (i.e., deep brain stimulation, electric and magnetic brain stimulation) and finally protocols of neurofeedback. We then develop more complex clinical and research concepts (e.g., combined cognitive training and brain stimulation along with cue exposure interventions).
2. Executive functioning, response inhibition, and self-regulation: terminological and theoretical clarifications
Numerous terms have often been used to describe similar concepts. For example, concepts such as self-regulation, inhibition, executive function, cognitive control, effortful processes, impulsivity, risk-taking, and disinhibition are sometimes clearly delineated but sometimes are used as synonyms or closely related concepts [24]. Attempts to clarify those concepts (e.g., the degree that some of those constructs overlap) have been scarce but mostly suggest that intrinsic aspects of regulation, self-regulation, serve as an umbrella concept that encompasses top-down and bottom-up processes that mutually influence one another [24, 25, 26]. Naturally, the influence of extrinsic aspects of regulation, that is, facilitated or hindered self-regulation due to others’ mind and action, is far to be negligible and should be considered to fully apprehend the determinants of dysregulated actions, such as addictive behaviors [27, 28].
2.1 Inhibition in definition
As suggested by William James, “Voluntary action, then, is at all times a resultant of the compounding of our impulsions with our inhibitions” [29]. In order to control the desire, the reason takes place as represented like Plato seeing the will as a charioteer attempting to control two horses (one of desire and one of reason) in Phaedrus. For both Hippocrates and Aristotle, the body and mind are not independent, but each influences the other. Long after, the fundamental duality between reason and emotion conferred to will the essence to control (or inhibit) action and emotion. A few decades later, Sherrington was awarded the 1932 Nobel Prize for Physiology and Medicine for his contribution to our understanding of inhibition in neurophysiology, which consolidated the concept.
Although creating a sense of comfort in theorizing, the explanation (e.g., brain structure in the frog that inhibits a spinal reflex) based on similarity to excitatory or inhibitory functions of the nervous system (i.e., neurons can serve either functions) that strong impulses can be impeded through the implementation of inhibition remains a debated matter [30].
Because of this warning, presenting an operational definition of “inhibition” remains an adventurous venture, not only because of the weight of its intuitive load (e.g., cognitive inhibition is equivalent to neural inhibition sometimes as metaphor) but also because of the phenomenon and explanation conflation or a confusion between a causal process and a functional relationship [31].
In most cases, response inhibition mainly refers to the suppression of actions that are no longer required or that are inappropriate, which supports flexible and goal-directed behavior in ever-changing environments [32]. As such, given its role in supervising ongoing thoughts and action in working memory, response inhibition has been considered as a hallmark of executive functions [33, 34]. As a form of top-down (intentional) inhibition process, prepotent response inhibition refers to deliberate inhibition operating on basic and reactive elements of action, which is essentially non-automatic and represents a cost. Intentional control depends on motivation and capacity [35]; it is subjectively deliberate, slow, and sequential; and it requires working memory and is capacity-limited.
However, a growing amount of data challenged this strictly hierarchical view [36, 37]. Indeed, executive control emerges from an interactive and competitive network generating biases in advance and is strongly influenced by personal recent and past experiences. Indeed, humans automatize as much as possible; hence apparent intentional inhibition can in fact operate automatically for particular contexts, due to context-inhibition associations made through learning. For instance, on the stop-signal task [32], when people are informed that they may have to stop a response in the near future, they typically slow down operation through altering activity in lower-level systems that are involved in stimulus detection, action selection, and action execution [38]. Put differently, instead of relying only on executive functioning, low-level and high-level systems work together for self-regulation.
Although closely related to executive functioning, response inhibition can be distinct from other forms of executive functions such as working memory update (i.e., the ability to replace information stored in working memory with new information) and switching (i.e., the ability to shift attention to other tasks or perceptual dimensions) [33] (see Figure 1).
Figure 1.
Executive function classification proposed by [33].
Based on latent variable analysis, several forms of response inhibition could be distinguished [39, 40, 41, 42]. A first distinction has been made between the inhibition of prepotent response and the resistance to distracter interference. However, the robustness of this two-factor solution remains questionable in light of low correlations between inhibition measures, when the contribution of memory processes was intentionally reduced [41]. It follows from this discussion that studies using a single laboratory paradigm for assessing or investigating inhibition do not warrant generalization beyond the specific paradigm studied.
More fine-grained forms of inhibition have been put forward across the years [39, 41]. Indeed, resistance to proactive interference consists of resisting memory intrusions from information that was previously relevant to the task but has since become irrelevant.
A second categorization relies on the degree of anticipation and preparation of response inhibition [43, 44]. Reactive inhibition (or reflexive inhibition) is a form of inhibition that one can implement without anticipation (e.g., stopping the car when an animal unexpectedly jumps on to the road). Proactive inhibition refers to the impact of inhibition preparation on the inhibitory performance (e.g., keeping one’s foot close to the brake after passing a warning sign for animals on the road). Possibly because proactive form of response inhibition requires much more than just inhibition, as attested by shared brain contribution of both forms of inhibition (the right inferior frontal gyrus, supplementary motor area and striatum) and also specific engagement of working memory-related regions (i.e., dorsolateral prefrontal region) [45], proactive inhibition may be more ecologically valid than reactive inhibition [46].
Sufficient agreement can be found on the contributions of these different inhibitory control mechanisms as measured by a variety of cognitive tasks described by Friedman and Miyake [39]. The list of tasks includes the color Stroop, anti-saccade, stop-signal, simon, global-local, and negative compatibility tasks that could share a component of inhibition of prepotent response; the letter flanker, the number Stroop, arrow flanker, and negative compatibility as well as the task assessing n-2 repetition costs tend to assess resistance to distracter interference.
3. Response inhibition and addiction
Consistent with the previous discussion, response disinhibition is an important element of modern addiction models [6, 9], and empirical data support this claim, particularly for gambling, psychostimulant, and alcohol addiction [5]. By conferring a central position to response inhibition, brain imaging and behavioral studies demonstrated abnormal functioning in individuals at risk to develop an addictive behavior, in addicted people, and in individuals who relapsed [9, 47, 48]. Indeed, a variety of response inhibition deficits are present in numerous forms of reinforcement pathologies (e.g., tobacco dependence [49, 50], alcohol disorder [51, 52], eating disorders [53, 54], gambling disorder [55] (but see [56])). Second, those deficits can predict relapse in drug and behavioral addiction [18, 57, 58], and research suggests that recently abstinent addicts experience heightened difficulties with response inhibition [59, 60]. Thirdly, the inability to stop one’s actions, due notably to early stressful life events and negative parent–child interaction [61], can influence behavioral and substance addictions later in life [17, 61].
In addition, it should be noted that impaired response inhibition has a strong impact in important aspects of decision-making. For instance, impaired prepotent response inhibition in alcoholics was associated with poorer performance on the Iowa gambling task [62], which requires participants to deal with uncertainty in a context of punishment and reward, with some choices being advantageous in the short term (high reward) but disadvantageous in the long run (higher punishment) and known for its ecological validity of decision-making [63, 64, 65]. Risk-taking could also be modulated through inhibitory control engagement, with participants being more cautious once anticipating to suppress their response [66]. Unfortunately, the benefit of this form of inhibitory training is fragile and transitory [67]. Besides, data from a sample of pathological gamblers revealed no effect of this procedure on risk-taking [68]. Finally, prepotent response inhibition can moderate the behavioral expression of implicit cognition [69]. Indeed, the impact of implicit cognitive processes on drinking behavior should be stronger in individuals with relatively weaker executive control than in individuals with relatively good executive control, as shown by using the classical Stroop interference scores [70]. Conversely, among adolescents with relatively good executive control, explicit expectancies were the best predictor of alcohol use [71].
In theory, prepotent response inhibition can directly be involved in myopic decision, that is, a preference for dominant sooner-smaller at the detriment of less salient larger-later decisions [72]. Steeper delay discounting rate is indubitable in individuals with addiction [73], which concurs to the risk of addiction and treatment response [74, 75]. In support of the existence of a relationship between prepotent response inhibition and short-termism, decreased gray matter volume in lateral prefrontal regions is associated with greater impatience [72, 76]. However, the level of inhibitory control, as typified by the stop-signal reaction time of the stop-signal task [32], and preference for large delayed rewards, as assessed using delay-discounting paradigms, are generally not correlated in both healthy participants [77] and clinical populations (e.g., in patients with attention deficit/and hyperactivity disorder) [78], which suggests that response inhibition and delay discounting are independent factors, each of them contributing to addiction.
4. Cognitive training
As mentioned earlier, several findings argued in favor of cognitive-based interventions aimed at targeting response inhibition as an assistant in preventing relapse in addicted population.
Amending those deficits is a huge endeavor and ways to achieve it is still a debated matter [79]. This section elaborates on several cognitive training interventions (CTI) that potentially impact positively on inhibition-related processes in individuals with reinforcement pathologies.
4.1 Restoring inhibitory control
Two contrasting approaches have been used to evaluate response inhibition training on substance use disorders and behavioral addiction: general stop inhibition with classical paradigms assessing prepotent response inhibition or with versions adapted to the type of addictive behaviors (e.g., alcohol Stroop test or cocaine go/no-go task).
Although there is no conclusive evidence of true increase in inhibitory control in response to extensive training with standard go/no-go or SST tasks in adults [80], training of inhibitory control reduced monetary risk-taking [66] and alcohol-seeking [81]; even this effect is small and short-lived [67, 68], which could potentially explain why some studies failed to observe far-transfer effects [82].
In contrast to some studies using formal training of working memory (e.g., [83]) to evaluate their direct impact on unhealthy behaviors (e.g., alcohol abuse), which can be positive in nonclinical samples [84], but not clinical population [85], modified versions of response inhibition tasks have served as training paradigms [79, 86, 87, 88, 89, 90].
During “inhibitory control training” (ICT), participants complete an inhibitory control task (go/no-go task, stop-signal task, anti-saccade task) in which the requirement to exercise inhibitory control is paired with cues related to healthy behaviors, before the effects of this training on the target behavior are measured (for reviews, see [79, 89, 91]). For example, when a group of participants in whom inhibition was paired with neutral cues was compared, participants who completed a stop-signal task in which alcohol images were paired with inhibition subsequently led to reduced ad libitum alcohol consumption in the laboratory, but not self-reported drinking in the week after training [90]. In the same vein, participants who learned to associate food images with inhibition on a go/no-go task subsequently consumed less of those foods when given access to them [88]. In contrast, training of oculomotor inhibition in the presence of alcohol-related cues led to slowed eye movements toward target cues on catch trials, but this manipulation failed to influence the proportion of inhibitory failures and had no influence on alcohol consumption in the laboratory [90]. Initial results indicated that the relationship between behavioral inhibition and alcohol intake may be causal, possibly to the ecological value of alcohol motor response inhibition paradigms (e.g., picking up a glass of alcohol beverage may be directly targeted by motor inhibition training), and training of oculomotor inhibitory control is far less convincing.
Meta-analytic approach [89, 91, 92] demonstrated that the effect of ICT on behavior was dependent on the task used. In theory, research on inhibition have led to the recognition that there are at least two types of inhibitory control: action restraint in which the decision to inhibit is made from the onset (go/no-go tasks) and action cancelation in which the decision to inhibit occurs after implementation of the prepotent response (stop-signal task) [93, 94]. However, the meta-analyses reveal that the higher the proportion of successful inhibitions of appetitive signals, the greater the magnitude of the effect of ICTs. Indeed, studies found a larger and more statistically robust ICT effect size when go/no-go rather than stop-signal tasks are used. One reason for the superiority of training action restrain on action cancelation [95, 96] is that compared to go/no-go tasks, stop-signal tasks have a lower rate of overall stop success that ends up hindering the development of strong stimulus-stop associations [53, 95]. Instead, go/no-go tasks feature strong stimulus-stop association due to the rate of successful inhibitions reflected in the number and proportion of stop-stimulus pairings, which in turn moderate the effects of training on unhealthy behavior. It is still in debate to ascertain what repeated stop-stimulus pairings could cause: better intentional inhibitory control over impulsive action [97], facilitated automatic retrieval of stimulus-stop associations [21, 37, 98], or diminished motivational properties of target information [99, 100, 101]. The issue of which mechanisms mediate the relationship between cognitive training paradigms and behavioral changes remains highly complex for several reasons. First, the size of behavioral change is at best rather small and does not survive more than a couple of hours [67]. Besides, it remains to be seen whether the control condition used in most of the studies where participants are required to rapidly respond to appetitive stimuli as often as inhibiting responses contributes to inflated effect size of ICT [89]. Second, there is no clear consensus on theoretical constructs such as motivation, where generally there is a weak relationship between implicit and explicit measures of stimulus evaluation [102]. Indeed, whereas a majority of studies using implicit motivational measures demonstrate no effect of inhibition of cognitive training on stimulus devaluation, other studies using Likert scale or other explicit procedures [101] demonstrated devaluation effects following this sort of intervention [103, 104, 105].
To sum up, general or cue-specific inhibition training has yielded only modest clinical results, and mechanisms remain to be elucidated.
4.2 Cognitive bias modification
Cognitive bias modification consists of pairing alcohol-related content with action tendencies, classically pushing a joystick in response the alcohol-related images and pulling the same joystick in response to soft drinks [106, 107]. Cognitive and clinical effects of this procedure have been compared to sham training conditions requiring an equal number of approach and avoidance movements to both alcohol and soft drinks pictures (i.e., no stimulus-response contingency). Main original outcomes are (a) reduced alcohol approach-related biases indicated with the implicit association task and (b) reduced alcohol relapse up to 1 year after the training. As suggested, an important mediating effect was the building of an alcohol-avoidance bias [106]. The clinical efficacy of this approach regardless of patients’ characteristics (age, number of prior detoxifications, etc.) has shown to be too limited to be integrated as such in clinical settings. Indeed, on a meta-analysis of 14 studies (mainly for alcohol and tobacco use problems) involving 2435 participants [22], the authors found a small, nonsignificant overall effect on cognitive bias assessed directly after the completion of the training intervention. In addition, neither smoking nor alcohol reduction was found in response to training intervention. In the same vein, a recent meta-analysis “cast serious doubts on the clinical utility of CBM interventions for addiction” [108]. In response to this assertion, influential researchers in the field, Wiers et al., argued that this analysis combined the results of laboratory and randomized controlled trials, which may underestimate CBM’s actual effectiveness when incorporated into regular therapy [109].
In addition to those theoretical and methodological limitations, several moderators could hinder yet existing ICT effects. It is the case of the degree of readiness to change, that is, the goal to gain control over harmful behaviors that make the ICT intervention more congruent with the participant’s mindset, hence potentiating its effects [110]. Another source of variation in the effect of ICT could be the strength of appetitive responses to food cues [111], with the effects of ICT on behavior being proportional to the strength of appetitive responses to cues before ICT [112, 113]. Whether individual differences in attempts to limit drinking, smoking, or gambling moderate the effects of ICT on alcohol intake is a promising avenue for future research. Put together with current literature revealing substance-specific relapse (and vulnerability)-related impairments, it is recommended to investigate cognitive training programs based on a patient-tailored protocol [114].
5. Brain neurostimulation techniques
5.1 Brain stimulations: noninvasive and invasive techniques
Effects of brain stimulation of basic processes, neurochemical regulation, and cognitive and affective processes at the system level have revealed promising results when applied to addiction treatment (for reviews and meta-analyses, see [23, 115, 116]). The most used stimulation techniques include deep brain stimulation, repetitive transcranial magnetic stimulation, and transcranial direct current stimulation known for their effect on self-regulatory processes and possibly acting on several forms of response inhibition.
5.2 Invasive brain stimulations
5.2.1 Deep brain stimulation
Despite ethical concerns due to potential serious side effects [117], deep brain stimulation has expanded from successful thalamic stimulation for Parkinsonian tremor (for a review, see [118]) to psychiatric conditions including addiction [23, 115, 116]. DBS is a neurosurgical procedure involving the placement of a neurostimulator, often called “brain pacemaker,” which delivers electrical impulses through implanted electrodes to specific brain regions related to abnormal functioning characterizing neurological and psychiatric conditions.
Back in the 1980s, BDS was introduced as treatment for movement disorders and became well known for treating the tremor of patients with Parkinson disease [119]. During the 2000s, it started to be applied in psychiatric disorders when the pathology is treatment-refractory: in obsessive-compulsive disorder (OCD) [120] and in major depression [121]. DBD gained interest as a means to treat addiction as soon as studies reported unintended alleviation of comorbid alcohol [115], nicotine [122], and gambling [123] addictions.
As reviewed by Luigjes et al. [124], based on a total of eight studies, bilateral high-frequency NAc stimulation in heroine dependence came with reduced craving and prolonged abstinence. In addition, animal studies have provided evidence that NAc DBS dampens impulsivity [125, 126], which represents a core aspect of addictive behaviors [127].
However, because of the absence of double-blind controlled trials in addiction, the cost and the invasiveness of the procedure, as well as the lack of consensus regarding its clinical efficacy and the encountered difficulties to recruit motivated participants [128], DBS to treat addiction could suffer from feasibility issues.
5.3 Noninvasive brain stimulations
Because they offer a safe economical way to modulate brain activity, techniques such as repetitive transcranial magnetic stimulation and transcranial direct current stimulation are growing in popularity for interventions in psychiatric disorder [129, 130]. They are so-called noninvasive to reflect the fact that the magnetic pulses are delivered from a coil placed over the scalp, without a surgical intervention (in contrast to DBS), which contributed to its popularity as techniques for modulating brain activity over the past two decades. Although recent reviews repeatedly recommended more clinical trials before firm conclusions about their efficacy could be drawn [124], their effects on key addictive-related phenomena (e.g., craving, impulsivity) are noteworthy [131].
5.3.1 Repetitive transcranial magnetic stimulation
Repetitive transcranial magnetic stimulation delivers in a time interval a magnetic pulse through the skull via a stimulating coil. The magnetic field involves a focal electrical current, depolarizing underlying cortical neurons. The intensity, duration, properties, localization, and frequency directly influence the effects. Low frequency (1–5 Hz) tends to produce inhibitory effects and fits well the intention of downregulating activity in the targeted regions [132, 133]. High frequency (10–20 Hz) tends to produce excitatory effects on the stimulated brain area. However, substantial inter-individual responses to both low- and high-frequency stimulation have been reported [134]. By using either figure-of-eight coils or H-coils known to produce highly focal stimulation in superficial cortex or deeper intracranial penetration to a more central target, respectively [135], the clinical influence of a variety of clinical phenomena has been investigated.
rTMS and addictive behaviors: The most frequently used rTMS setup has been 10 sessions of stimulation on either the right DLPFC with a high frequency or the left DLPFC with lower frequency. In nicotine addiction, frequently reported findings include reduced transitory (no longer than several weeks following the intervention) cue-induced craving for cigarette as well as lower nicotine consumption [136, 137]. Interestingly, an important placebo effect has been repeatedly found in rTMS studies. Indeed, a reduction in the daily consumption of alcohol [138] or cocaine [139] has been found in response to both active and sham stimulation. In the same vein, although a reduced attentional bias toward alcohol cues has been found in response to high-frequency left DLPFC rTMS, all participants (irrespective of their stimulation condition) reported a reduced craving [140]. The placebo response should be due to a concurrent treatment regimen, which too often is missing from these studies, and better study designs should involve participant blinding.
Regarding the clinical impact of rTMS in behavioral addiction (e.g., gambling addiction, binge eating), the insufficient number of controlled trials prevents drawing conclusion [23].
An important issue to be discussed is the potential cognitive mediators of rTMS effects in addicted subjects. In theory, a reduction in craving intensity and in substance use could be mediated by improved response inhibition or mental flexibility or a change in salience or automatization. No effects above sham stimulation were found on prepotent response inhibition evaluated by a go/no-go task [141].
Although DLPFC is critical for cognitive-executive functions, stimulation of medial regions tends to influence affective-motivational functions [142]. This region along with others such as the insula is important for the selection of long-term over short-term reward, an interplay that may be abnormal in individuals with addictive behaviors [143, 144]. Magnetic stimulation of the medial prefrontal cortex may bias the preference for delayed, over sooner, rewards [145]. However, this encouraging view has been recently tempered by a study reporting the absence of effect of rTMS targeting the medial prefrontal cortex on impulsive choice on the delay discounting task in pathological gamblers [146].
In contrast to rTMS that requires 20–30 min of stimulation time to achieve its full effect, theta burst stimulation (TBS) protocols could achieve similar efficiency by employing protocols lasting between 20 s and 3 min that induce NMDA receptor-dependent long-term potentiation and long-term depression [147]. A recent meta-analytic review [148] that focused on healthy participants on the prefrontal cortex with theoretically linked cognitive test performance as the outcome revealed that uninterrupted train of TBS decreases performances on measures of inhibitory control, attentional control, and working memory, whereas intermittent TBS has positive effects on executive functions (but not likely ceiling effects). Future studies comparing different magnetic stimulation protocols should be conducted in the context of addictive behaviors.
5.3.2 Transcranial direct current stimulation
Transcranial direct current stimulation involves delivering low-intensity electric current (typically 0.5–2 mA) via electrodes placed on the scalp and/or upper body. Cortical excitability is modulated by a polarity-dependent shift of the neuronal membrane potential [149, 150]. On the macroscopic level, anodal stimulation enhances cortical excitability via depolarization and long-term potentiation, whereas cathodal stimulation inhibits excitability via hyperpolarization and long-term depression [149]. The density, duration, and direction of the current that comes into contact with underlying neurons determine the strength and direction of neuromodulation [149, 150]. After an initial subthreshold depolarization or hyperpolarization of neuronal membrane potentials that increases or decreases the likelihood of spontaneous neural firing, facilitation of long-term potentials or long-term depression occurs [151]. tDCS modulation of the action potentials even lasts beyond the stimulation period [149, 150], and several neuromodulation sessions could increase the duration of the effects [152].
tDCS as an intervention in addictive disorders: a recent review [23] showed that seven published studies have focused on the impact of tDCS on various measures related to substance addiction. Despite important inter-individual differences in response to tDCS [153], most preeminent effects were found on craving reduction [154]. In addition, mixed results were found with respect to executive control functions [124, 131, 155, 156]. Importantly, in healthy controls no improvement was found after tDCS stimulation of bilateral DLPFC stimulation of either right anodal/left cathodal or left anodal/right cathodal on decision-making under risk (e.g., balloon analogue task), an absence of effect possibly due to a ceiling effect [157].
The benefit from reducing cue-induced craving for clinical population could be pertinent. Indeed, pressing, urgent, and irrepressible desire to drink or to smoke has been strongly associated with loss of control, leading to a high relapse rate [158]. However, the mediating effect of craving variation in response to tDCS on relapse is not obvious. For instance, in a tDCS study in patients with alcohol dependence (two daily stimulations 5 consecutive days on left cathodal/right anodal over the dorsolateral prefrontal cortex), no differences with regard to changes on scores of craving were found despite an improved overall perception of quality of life and reduced relapse probability in several alcoholics [159]. In nicotine addiction, right anodal stimulation on the DLPFC reduces craving with minimal heterogeneity, whereas cathodal tDCS on this region showed the most positive effect on cue-provoked craving and smoking intake [154]. However, this craving reduction, which may be due to increased control on cue reactivity, could be too small to positively impact cigarette use. Indeed, as compared to sham, active tDCS significantly reduced smoking craving and increased brain reactivity to smoking cues within the right posterior cingulate, as measured with a functional magnetic resonance imaging event-related paradigm, but failed to diminish the number of cigarettes smoked (see also [160]) and the exhaled carbon monoxide 1 month following the stimulation [161].
Regarding the association between tDCS and food, reduction of food craving [162, 163, 164] and calorie intake [97] in healthy subjects and reduced craving for food in overweight subjects [165] have been reported.
Mediating processes involved in brain stimulation of the PFC is likely to be more complex than previously expected. It was demonstrated that anodal tDCS applied over frontoparietal regions has previously been shown to enhance attention and executive control functions [166, 167, 168], but the effects are limited and non-lasting.
Working memory, depending on the stimulation modalities, can be a valid candidate mediator [169]. As a multicomponent system responsible for temporary storage and manipulation of information, working memory sustained emotional regulation [14]. Because many psychiatric disorders are associated with working memory impairments, it may be useful to improve the transient “online” manipulation of emotional thoughts in treatment rehabilitation.
Response inhibition is another good candidate mediator of the relationship between tDCS and clinical change. For instance, a recent study showed that tDCS over the right inferior frontal cortex made healthy participants more efficient in proactive, but not reactive, inhibition [170]. In another study, tDCS over the pre SMA during a stop-signal task increases activity in the pre SMA after anodal stimulation during stop trials and was associated with improved inhibitory control [171]. Finally, after applying tDCS over the rIFG, two studies [170, 172] observed a decrease in P3 amplitude during no-go and/or stop trials in anodal compared to inactive stimulation. The clinical value of those results in the case of addictive behaviors remains to be seen. One possibility is that a reduction of P3 amplitude during successful response inhibition on a go/no-go task in response to tDCS could be a protective factor for the risk of relapse in vulnerable alcoholics, that is, those with greater amplitude of P3 [173].
The clinical impact of tDCS on substance use can be still more subtle. For instance, in obese participants, electric brain stimulation on the DLPFC facilitated the transition between unconscious and conscious perception of appetitive stimuli, a phenomenon particularly pronounced in participants with higher body mass index [174]. Those findings could have an impact on craving regulation, via augmented awareness of implicit determinants of craving, enhancing the risk of relapse.
Although the proposed cognitive mediators presented in this section showed promising results, their clinical relevance is still tentative. Much more data is needed to achieve a better comprehension of the impact of tDCS on addictive behaviors.
5.3.3 Neurofeedback
In neurofeedback, participants learn to modulate their own brain activity through feedback. The main goal is for participants to develop effective self-regulation strategies to increase desired brain activity. Functional magnetic resonance imaging neurofeedback (fMRI-NF) and electroencephalography neurofeedback (EEG-NF) are the most developed configurations [175], each with its strengths and weaknesses [176, 177]. Higher spatial resolution and broad brain coverage characterize fMRI-NF [178], while EEG-NF has very good timing but low spatial accuracy. In EEG-NF, it is possible to modify neuronal oscillations in specific frequency domains associated with functions such as attention or relaxation. fMRI-NF and its variant, real-time fMRI [179], provide direct feedback to modulate (increase or decrease) neuronal activity in the regions of interest [180]. With fMRI-NF, brain regions of interest are defined a priori on the basis of consensual articles describing which neurocognitive networks are altered and predictive of low use of controlled substances [181]. In EEG-NF, critical oscillations in certain frequency bands have been associated with mental states (e.g., alpha and theta frequencies for a relaxed or meditative state, beta rhythm, or sensorimotor for inhibition).
In the context of addictive behaviors, alpha-theta and the alpha-theta augmented with SMR training represent the two main protocols of EEG-NF. As pointed out by [23], only a few studies have reached a reasonable quality (only one study used a control condition matched in time) [182], which makes it difficult to determine which protocol provides the best results. However, in two studies [182, 183], a reduction in the number of false alarms (i.e., response to no-go trials) on a go/no-go task was observed in participants who received EEG-NF rather than an alternative treatment. It is interesting to note that sensorimotor interferences can be reduced in healthy participants who undergo SMR neurofeedback training, which they have learned to voluntarily increase, resulting in better cognitive performance [184].
With respect to fMRI-NF, an analysis based on eight studies [23] revealed that six of them performed on nicotine addiction showed better regulation at the level of the anterior part of the cingulate gyrus directly associated with a decrease in the desire to smoke [185]. In alcohol addiction, reduced craving was achieved by modifying activity in the ACC, PFC, and insula [186]. Further studies should explore reward (e.g., ventral striatum) and control processing before the clinical relevance in addiction could be confirmed and mediating factors (e.g., prepotent response inhibition) identified.
6. A step forward: combined interventions with retrieval-extinction techniques
Coupling brain stimulation with other pharmacological and non-pharmacological interventions may provide further knowledge about individual brain oscillation states across several montages and voltages as well as long-term structural and functional effects of brain stimulation on addicted patients [187]. These proposals will certainly make better use of brain stimulation techniques and therefore optimize their clinical effects (Table 1).
Here we focused more on the effects of combined interventions to improve clinical efficacy. Combined methodologies have provided positive clinical results in a variety of psychiatric conditions [188]. From a broad perspective, the use of neuromodulation techniques to promote brain plasticity [189, 190] while exerting response inhibition, extinction learning, or cognitive restructuration may help regain control over prepotent actions.
Brain stimulation and investigation techniques
Deep brain stimulation (DBS)
A small device, similar to a pacemaker, is surgically implanted to deliver electrical stimulation to targeted areas of the brain
Transcranial direct current stimulation (tDCS) and its variant, the transcranial alternating current or random noise stimulation
Allows changes in cortical activity to be generated by inducing a direct low-intensity (1–2 mA) current in the brain
Repetitive transcranial magnetic stimulation (rTMS)
Induces repeated single magnetic pulses in the brain to modulate cortical activity
Event-related potentials (ERP)
By means of electrodes placed at various points on the scalp and amplified through an EEG machine, the ERP measures electrical potentials generated by the brain in response to specific internal or external events (e.g., sensory, cognitive, or motor stimuli)
Function magnetic resonance imagery (fMRI)
To detect regional and time-varying changes in brain metabolism and blood oxygenation
Cognitive training and related cognitive functions
Domain-general cognitive training
A structured practice of mental abilities that are used to solve complex tasks regardless of their content (e.g., working memory)
Domain-specific cognitive training
A structured practice of mental abilities where the semantic content of the processed information is controlled (e.g., negative emotional words or alcohol-related content)
Cognitive biases
These refer generally to unidentified or inaccurately identified attitudes or stereotypes, but in the present essay, we reported attentional, memory, and action tendency biases as normal and abnormal manifestations of domain-specific processing (e.g., attentional engagement toward smoking cues in deprived smokers)
Cognitive deficits
Describes a deviation from the normal functioning of general cognitive domains (e.g., episodic memory, executive functioning)
Executive functions
Partially independent, top-down processes reflecting goal cognitive corresponding to an internal goal are involved in the control of behavior, emotions, and cognition. The updating of the relevant information, the inhibition of prepotent impulses, and the mental set shifting are core functions
Proactive control
Refers to expectancy-based activation of cognitive control (maintaining goal activation to bias responding) prior to an anticipated conflict or challenge. In contrast, reactive control refers to the activation of cognitive control after a change or conflict is detected
Working memory
The ability to hold multiple things in mind at once while mentally manipulating one or more of them (e.g., updating)
Interference control
Ignoring (inhibiting, suppressing, or deactivating) internal or external competing information to protect working memory or to focus attention on goal-relevant information
Prepotent inhibition response
Refers to the suppression of actions that are no longer required or that are inappropriate, which supports flexible and goal-directed behavior in ever-changing environments
Self-regulation
Encompasses cognitive control, emotion regulation, and top-down and bottom-up processes that alter emotion, behavior, or cognition to attempt to enhance adaptation (or to achieve an explicit or implicit goal or goal state)
Learning-related concepts
Conditioned stimulus
A previously neutral stimulus that has been learned to predict an outcome; the presentation of the stimulus evokes the memory of the previous learning
Extinction
The presentation of a conditioned/learned stimulus now in the absence of the previously associated outcome; this results in the temporary decline of subsequent memory expression
Learning
The behavioral changes of an organism are the result of regularities in the environment of that organism
Reactivation
Re-exposure to memory reminders, which may result in destabilization of the previously learned neural representation of memory
Retrieval
A reminder results in recollection of the previously learned memory; the term encompasses the multiple processes from reactivation of the neural memory representation to behavioral expression of the memory
Reconsolidation
The active process that is necessary to restabilize a reactivated/destabilized memory; disruption of reconsolidation results in memory impairment, while new information is incorporated during reconsolidation into an updated memory
Reactivation-extinction (retrieval-extinction)
The combination of memory reactivation (usually via a reminder that results in memory retrieval) and, after a brief interval, subsequent extinction
Table 1.
Definitions and glossary of major terms as relevant in the current essay.
As shown in Table 2, only five studies used several combined approaches in the context of substance use disorders. The results are rather disappointing. Indeed, in five out of five studies, no interaction between brain stimulation and cognitive manipulation was found, indicating that tDCS did not add any clinical value to behavioral training. However, two studies have examined the combined effects of left anodal tDCS on DLPFC and cognitive-behavioral modification (CBM) in high-risk drinkers undergoing or not treatment. In the high-risk drinker sample, 1.0 mA was administered on left DLPFC during three CBM sessions for 3 to 4 days. No effect of CBM or tDCS was observed on approach bias or alcohol consumption. However, participants reported a reduced craving during a signal responsiveness task [191]. In treatment seekers, 2.0 mA over left DLPFC over the course of four training sessions in 4 consecutive days was used [192]. No significant interaction effect for the full sample was found. However, in this study, there were some indications of a boosting effect of tDCS and CBM, such that relapse was lower in this group at the 1-year follow-up.
No effect of repeated CBM and/or tDCS on 3 months of abstinence duration, craving, and alcohol biases, except a trend-level effect of active tDCS during active training on relapse rate at 1 year only when comparing to sham tDCS (p = .07)
Stronger avoidance bias only during training session in active tDCS with active ABM (p < 0.05) No effects of tDCS and ABM on the bias scores, craving, or relapse
Effect of combining CBM and tDCS on reduction of alcohol approach biases and alcohol consumption
At-risk alcohol drinkers AUDIT > 8
History of treatment for AUD or desire for treatment Alcohol withdrawal Brain injury Psychotropic medications Pregnancy Illicit drug use Metal in the body
79
24.5 (2.7)
Not indicated
2 × 2 factorial design:
Active tDCS during active training
Sham tDCS during active training
Active tDCS during sham training
Sham tDCS during sham training
Four sessions (of 1 h per week, 4 consecutive weeks) of AABR** while tDCS right inferior frontal gyrus (2 mA; 20 min; 11 cm2 anode F10 and the cathode arm)
Drinks per drinking day (DDD) and percent heavy drinking days (PHDD) at baseline, the follow-up visits at 1-week and 1-month follow-ups, alcohol approach bias at baseline
Significant alcohol approach biases at baseline; neither CBM, tDCS, nor the interaction reduced the bias at the follow-up No significant effect of intervention on either DDD or PHDD
Table 2.
Effect of tDCS and behavioral interventions combined in substance use disorder.
tDCS criteria: epilepsy, multiple sclerosis or other neurological illness, previous brain injury/infection, metal in the brain, pacemaker, pregnancy, claustrophobia, recent fainting/panic attack, frequent headaches or dizziness, and eczema or other skin conditions
Alcohol Approach Bias Retraining: pull or push alcohol or soft drink pictures with joystick.
Attentional Bias Modification: dot-probe training task with alcohol, nonalcohol, or object pictures
Inhibitory control training: a go/no-go training task with fatty food, healthy food, and close pictures
More encouraging evidence for the usefulness of a combined approach comes from research on patients with mood disorders. For instance, participants with social anxiety disorder had a significant decrease in attention bias for threatening signals during single anodal stimulation as opposed to simulated stimulation [196]. In obsessive-compulsive disorder, exposure to information aimed at generating a conditioned response (e.g., increase anxiety in response to a risk of contamination) has been tested in combination with tDCS [197] or rTMS [198]. Indeed, by using a personalized provocation of symptoms aimed at generating an appropriate level of distress, the goal was to activate the corresponding neural circuit. During brain stimulation, people were asked to think about provocation (“Please keep thinking about your dirty hands”). Positive results were found in this combined setting (brief exposure therapy + tDCS or rTMS). In the field of nicotine addiction, one study has shown that it is advantageous to use a challenge with actual exposure to tobacco signals just prior to the rTMS high-frequency stimulation treatment [199]. It should be noted that this approach requires that the interventions be individualized according to the conditioned responses involved in the addictive process.
Brain stimulation techniques could also be advantageously coupled with interventions targeting the learning process of extinction in addictive disorder. Extinction refers to the disappearance of a conditioned behavior in the absence of positive or negative reinforcement [200]. Extinction is the basis for an intervention based on exposure, a primary treatment for a variety of psychiatric conditions, including addiction [201]. Unfortunately, the extinguishing procedures did not simply wipe out the conditioned responses of the past, as shown by the return of the targeted behavior by extinction which is again apparent after the passage of time, after the presentation of the unconditioned stimulus, and when extinguished signals are encountered outside the extinction context [201]. Instead, extinction may be a new form of learning that exists with extinction memories in distinct neural circuits [202]. Therefore, increased extinction with new approaches has been extensively studied in animals and, more recently, in humans with aversive responses (e.g., fear) and appetite disorders (e.g., addiction) [203]. The extinction of the conditioned response may be more effective if it is preceded by a brief exposure to the conditioned response, that is to say, a phase of reactivation of the memory [204, 205, 206]. This approach, often named super-extinction, gave rise to theories of synaptic consolidation [207], which brought a fresh look at memory processes involved in flexible actions. Briefly, once activated, conditioned responses are rendered labile and unstable that interfering intervention (e.g., propranolol administration [208], non-pharmacological manipulation [209, 210]) ensuing during the reconsolidation window could update original memory traces [204]. Reduced involvement of the inhibitory networks [211] and induced plasticity [209] during extinction following reactivation could represent some of the key mechanisms in play. Importantly, whereas in extinction amygdala’s representation remains intact, the prefrontal activated reconsolidation would eliminate the necessity of such inhibition [211]. Additionally, as shown in animal studies, one factor that may initiate memory destabilization and reconsolidation is the detention of prediction errors (surprise effect) [212, 213]. In humans, some procedures combining prediction errors and memory reconsolidation interference have yielded interesting results in subjects with high alcohol consumption ([214, 215], p. 20; [216]). Although the clinical impact of those essays was not overwhelming, subtle changes of alcohol attractiveness have already been highlighted, such as a reduction of craving for alcohol [216] and significant reductions in verbal fluency for positive alcohol-related words [215]. In theory, conditioned stimuli could be erased with a single treatment, which could solve the compliance problems necessary to continue treatment, promoting abstinence [217]. Although promising and extremely relevant in the context of the prevention and treatment of addictive behaviors, the precise recovery conditions required to successfully destabilize memory remain unclear (e.g., role of prediction error, type of intervention post-activation, counter-conditioning, interference, extinction).
We suggest here that the super-extinction procedure can be implemented in combination with brain stimulation techniques and cognitive response inhibition training, for example, which may lead to stronger and more prolonged clinical effects in drug and behavioral addictions. Indeed, not only is the activation of relevant brain circuitry important before the application of brain stimulation [197, 198, 199], but it is also possible to capitalize on the lability of memory during reconsolidation. Indeed, reactivated memory becomes labile after retrieval through a process known as memory reconsolidation. Memory reconsolidation after retrieval may be used to maintain or update long-term memories, reinforcing or integrating new information into them [204, 205, 206, 209], a phenomenon that would underlie change in psychotherapy [218]. Interestingly, decreasing DLPFC activity has been observed in repeated encounters with memories (e.g., [115]), resulting in a stabilization of memory. Consistently, the stimulation of the control network via an anodal TDCS applied to the right DLPFC during repeated access to acquired information disrupts the long-term retention of these memories [219]. Based on these findings, it is likely that stimulating the control network during reconsolidation of emotional memories associated with addictive behaviors could result in disrupted storage, particularly in circumstances that generate interferences (e.g., training alcohol-stop associations). Future research is needed to test these hypotheses and shed new light on this theoretical reasoning.
Another promising possibility is that cognitive training works better when combined with other forms of clinical intervention aimed at enhancing motivation, self-esteem, family functioning, social support, etc. [220]. In other words, a very interesting line of research is to study the interaction between the mechanisms involved in clinical interventions that lead to positive outcomes and the aforementioned cognitive interventions. Too often, clinical interventions have been described simply as a set of technical tools (e.g., CBT, family therapy) instead of mechanisms and processes of clinical interventions (e.g., compensatory skills, self-understanding) [221], which is a problem when we consider that each participant does not respond in the same way to a given intervention. For this reason, it may be that only the participants who benefit most in some way from a given clinical intervention are those for whom cognitive training and brain stimulation work best. It is obvious that the weakness of this hypothesis is precisely the problem encountered by research in identifying central mechanisms and methods related to psychological change in response to clinical interventions [222].
Finally, some studies have found that addicted participants have preserved automatic inhibitory resources [52]. In this study, recently detoxified alcoholics and healthy participants performed a modified stop-signal task that consisted of a training phase in which a subset of the stimuli was consistently associated with stopping or going and a test phase in which this mapping was reversed. In the training phase, stop performance improved for the consistent stop stimuli, compared with control stimuli that were not associated with going or stopping. In the test phase, go performance tended to be impaired for old stop stimuli. Combined, these findings support the automatic inhibition hypothesis. Importantly, performance was similar in both groups, which indicates that automatic inhibitory control develops normally in individuals with alcoholism. Furthermore, clinical interventions aimed at potentiating the automatic suppression of alcohol-going associations combined with procedures encouraging the automatic selection of alternative responses (e.g., intention implementation [223]). This approach has the merit to promote better inhibitory control of the action without saturating the resources of effortful self-regulation. Whether intensive addiction cues/stop associations could benefit from reactivation of craving or negative emotions is an important hypothesis to be tested in further experiments.
7. Concluding remarks
Many efforts have been made to modify the acquired motivational properties of addiction cues and to reinforce the control of prepotent responses via cognitive training, brain stimulation, and neurofeedback protocols. To date, our review has highlighted some of the promises as well as the obstacles that we need to overcome. In keeping with recent narrative critiques and the meta-analytic approach, the current state of the art appears to be like a half-empty or half-full glass. On the one side, an important limitation is the absence of a robust consensus about methods and mechanisms of brain stimulation techniques (but see for a recent consensus, article [224]) and recent findings calling into question inhibition as a psychometric construct [41]. The main consequence of this is the high level of variation between subjects in response to brain stimulation as well as a poor understanding of the precise cognitive mechanisms that mediate the efficacy of brain stimulation. On the other side, the glass could be considered half-filled because a reduction in the state of cue-induced craving is now feasible and the ongoing research on possible moderators could add important information. Indeed, the motivation for change of participants that refers to personal goals and values is a clinical target requiring specific psychological interventions before cognitive and brain enhancement can turn into robust clinical effects [109]. Clearly, the brain (e.g., using EEG or fMRI) and cognitive (e.g., impaired executive functions, exacerbated approach tendencies toward addiction cues) profiles of patients sensitive to cognitive improvement are important factors to identify [114, 225].
In this chapter, we also strongly recommend that conditioned stimuli and conditioned responses that lead to the loss and recovery of control of addictive behavior be better identified and used with retrieval-extinction techniques in combination with brain and cognitive stimulations. If ethical questions arise when unpleasant sensations are felt by people seeking care and when an intervention alters the substance of a memory, as it may disrupt a sense of self, we must remember the lack of effectiveness of contemporary clinical and experimental treatments in an intolerable situation which we have become too accustomed. We hope to have convinced the reader that in reconsolidation-based treatments, even if boundary conditions begin to be discovered [226, 227], the potential benefits may far outweigh the risks.
It is difficult to obtain better cognitive control, such as improving executive functions in adults, as shown by considerable data [80], but capitalizing on preserved automatic inhibitory resources could prove useful for promoting better inhibitory control of the action without saturating the resources of effortful self-regulation [21, 52].
In sum, these are exciting days where a number of key elements useful to change addictive behaviors have now been identified, yet their perfect fit remains to be done. What is also promising is the undeniable need to bridge the gap between experimental studies and clinical issues in taking into account motivation, relevant personal conditioned responses, acute and chronic stress, memory, response inhibition, and brain and cognitive stimulation to provide addicts with better control of their impulse and obsessions because it is often a prerequisite to return to a satisfactory quality of life.
\n',keywords:"addiction, inhibition, brain stimulation, memory reconsolidation, cue exposure",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/68856.pdf",chapterXML:"https://mts.intechopen.com/source/xml/68856.xml",downloadPdfUrl:"/chapter/pdf-download/68856",previewPdfUrl:"/chapter/pdf-preview/68856",totalDownloads:812,totalViews:0,totalCrossrefCites:2,totalDimensionsCites:4,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:69,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"March 25th 2019",dateReviewed:"July 28th 2019",datePrePublished:"October 16th 2019",datePublished:"April 22nd 2020",dateFinished:"August 29th 2019",readingETA:"0",abstract:"Addiction behaviors are characterized by conditioned responses responsible for craving and automatic actions as well as disturbances within the supervisory network, one of the key elements of which is the inhibition of prepotent response. Interventions such as brain stimulation and cognitive training targeting this imbalanced system can potentially be a positive adjunct to treatment as usual. The relevance of several invasive and noninvasive brain stimulation techniques in the context of addiction as well as several cognitive training protocols is reviewed. By reducing cue-induced craving and modifying the pattern of action, memory associations, and attention biases, these interventions produced significant but still limited clinical effects. A new refined definition of response inhibition, including automatic inhibition of response and a more consistent approach to cue exposure capitalizing on the phase of reconsolidation of pre-activated emotional memories, all associated with brain and cognitive stimulation, opens new avenues for clinical research.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/68856",risUrl:"/chapter/ris/68856",book:{id:"8938",slug:"inhibitory-control-training-a-multidisciplinary-approach"},signatures:"Xavier Noël, Antoine Bechara, Mélanie Saeremans, Charles Kornreich, Clémence Dousset, Salvatore Campanella, Armand Chatard, Nemat Jaafari and Macha Dubuson",authors:[{id:"90814",title:"Dr.",name:"Xavier",middleName:null,surname:"Noel",fullName:"Xavier Noel",slug:"xavier-noel",email:"xnoel@ulb.ac.be",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Université Libre de Bruxelles",institutionURL:null,country:{name:"Belgium"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Executive functioning, response inhibition, and self-regulation: terminological and theoretical clarifications",level:"1"},{id:"sec_2_2",title:"2.1 Inhibition in definition",level:"2"},{id:"sec_4",title:"3. Response inhibition and addiction",level:"1"},{id:"sec_5",title:"4. Cognitive training",level:"1"},{id:"sec_5_2",title:"4.1 Restoring inhibitory control",level:"2"},{id:"sec_6_2",title:"4.2 Cognitive bias modification",level:"2"},{id:"sec_8",title:"5. Brain neurostimulation techniques",level:"1"},{id:"sec_8_2",title:"5.1 Brain stimulations: noninvasive and invasive techniques",level:"2"},{id:"sec_9_2",title:"5.2 Invasive brain stimulations",level:"2"},{id:"sec_9_3",title:"5.2.1 Deep brain stimulation",level:"3"},{id:"sec_11_2",title:"5.3 Noninvasive brain stimulations",level:"2"},{id:"sec_11_3",title:"5.3.1 Repetitive transcranial magnetic stimulation",level:"3"},{id:"sec_12_3",title:"5.3.2 Transcranial direct current stimulation",level:"3"},{id:"sec_13_3",title:"5.3.3 Neurofeedback",level:"3"},{id:"sec_16",title:"6. A step forward: combined interventions with retrieval-extinction techniques",level:"1"},{id:"sec_17",title:"7. Concluding remarks",level:"1"}],chapterReferences:[{id:"B1",body:'Miller PM, Book SW, Stewart SH. Medical treatment of alcohol dependence: A systematic review. International Journal of Psychiatry in Medicine. 2011;42(3):227-266'},{id:"B2",body:'Borsboom D, Cramer A, Kalis A. Brain disorders? Not really… why network structures block reductionism in psychopathology research. The Behavioral and Brain Sciences. 2018;24:1-54'},{id:"B3",body:'Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: Neuroimaging evidence for the involvement of the frontal cortex. The American Journal of Psychiatry. 2002;159(10):1642-1652'},{id:"B4",body:'Goldstein RZ, Volkow ND. Dysfunction of the prefrontal cortex in addiction: Neuroimaging findings and clinical implications. Nature Reviews. Neuroscience. 2011;12(11):652-669'},{id:"B5",body:'Lee RSC, Hoppenbrouwers S, Franken I. A systematic meta-review of impulsivity and compulsivity in addictive behaviors. Neuropsychology Review. 2019;29(1):14-26'},{id:"B6",body:'Noël X, Brevers D, Bechara A. A neurocognitive approach to understanding the neurobiology of addiction. Current Opinion in Neurobiology. 2013;23(4):632-638'},{id:"B7",body:'Redish AD, Jensen S, Johnson A. A unified framework for addiction: Vulnerabilities in the decision process. The Behavioral and Brain Sciences. 2008;31(4):415-437 discussion 437-487'},{id:"B8",body:'Tang Y-Y, Posner MI, Rothbart MK, Volkow ND. Circuitry of self-control and its role in reducing addiction. Trends in Cognitive Sciences. 2015;19(8):439-444'},{id:"B9",body:'Zilverstand A, Huang AS, Alia-Klein N, Goldstein RZ. Neuroimaging impaired response inhibition and salience attribution in human drug addiction: A systematic review. Neuron. 2018;98(5):886-903'},{id:"B10",body:'Bechara A, Noel X, Crone EA. Loss of willpower: Abnormal neural mechanisms of impulse control and decision making in addiction. In: Handbook of Implicit Cognition and Addiction. Thousand Oaks, California: Sage publications, Inc., 2006. pp. 215-232'},{id:"B11",body:'Noël X, Bechara A, Brevers D, Verbanck P, Campanella S. Alcoholism and the loss of willpower: A neurocognitive perspective. Journal of Psychophysiology. 2010;24(4):240-248'},{id:"B12",body:'Noël X, Van Der Linden M, Bechara A. The neurocognitive mechanisms of decision-making, impulse control, and loss of willpower to resist drugs. Psychiatry (Edgmont (Pa.: Township)). 2006;3(5):30-41'},{id:"B13",body:'Evans JSBT. Dual-processing accounts of reasoning, judgment, and social cognition. Annual Review of Psychology. 2008;59:255-278'},{id:"B14",body:'Hofmann W, Schmeichel BJ, Baddeley AD. Executive functions and self-regulation. Trends in Cognitive Sciences. 2012;16(3):174-180'},{id:"B15",body:'Argyriou E, Davison CB, Lee TTC. Response inhibition and internet gaming disorder: A meta-analysis. Addictive Behaviors. 2017;71:54-60'},{id:"B16",body:'Lipszyc J, Schachar R. Inhibitory control and psychopathology: A meta-analysis of studies using the stop signal task. Journal of the International Neuropsychological Society: JINS. 2010;16(6):1064-1076'},{id:"B17",body:'Nigg JT, Wong MM, Martel MM, Jester JM, Puttler LI, Glass JM, et al. Poor response inhibition as a predictor of problem drinking and illicit drug use in adolescents at risk for alcoholism and other substance use disorders. Journal of the American Academy of Child and Adolescent Psychiatry. 2006;45(4):468-475'},{id:"B18",body:'Noël X, Sferrazza R, Van Der Linden M, Paternot J, Verhas M, Hanak C, et al. Contribution of frontal cerebral blood flow measured by (99m)Tc-Bicisate spect and executive function deficits to predicting treatment outcome in alcohol-dependent patients. Alcohol and Alcoholism. 2002;37(4):347-354'},{id:"B19",body:'Whelan R, Watts R, Orr CA, Althoff RR, Artiges E, Banaschewski T, et al. Neuropsychosocial profiles of current and future adolescent alcohol misusers. Nature. 2014;512(7513):185-189'},{id:"B20",body:'Noël X, Brevers D, Bechara A. A triadic neurocognitive approach to addiction for clinical interventions. Frontiers in Psychiatry. 2013;4:179'},{id:"B21",body:'Verbruggen F, Best M, Bowditch WA, Stevens T, McLaren IPL. The inhibitory control reflex. Neuropsychologia. 2014;65:263-278'},{id:"B22",body:'Boffo M, Zerhouni O, Gronau QF, van Beek RJJ, Nikolaou K, Marsman M, et al. Cognitive bias modification for behavior change in alcohol and smoking addiction: Bayesian meta-analysis of individual participant data. Neuropsychology Review. 2019;29(1):52-78'},{id:"B23",body:'Luigjes J, Segrave R, de Joode N, Figee M, Denys D. Efficacy of invasive and non-invasive brain modulation interventions for addiction. Neuropsychology Review. 2019;29(1):116-138'},{id:"B24",body:'Nigg JT. Annual research review: On the relations among self-regulation, self-control, executive functioning, effortful control, cognitive control, impulsivity, risk-taking, and inhibition for developmental psychopathology. Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2017;58(4):361-383'},{id:"B25",body:'Diamond A. Executive functions. Annual Review of Psychology. 2013;64:135-168'},{id:"B26",body:'Zhou Q , Chen SH, Main A. Commonalities and differences in the research on Children’s effortful control and executive function: A call for an integrated model of self-regulation. Child Development Perspectives. 2012;6(2):112-121'},{id:"B27",body:'Fals-Stewart W, O’Farrell TJ, Hooley JM. Relapse among married or cohabiting substance-abusing patients: The role of perceived criticism. Behavior Therapy. 2001;32(4):787-801'},{id:"B28",body:'Sripada CS, Angstadt M, McNamara P, King AC, Phan KL. Effects of alcohol on brain responses to social signals of threat in humans. NeuroImage. 2011;55(1):371-380'},{id:"B29",body:'James W. Talks to Teachers on Psychology: And to Students on Some of Life’s Ideals. New York: H. Holt; 1899'},{id:"B30",body:'MacLeod C, Dodd M, Sheard E, Wilson D, Bibi U. In opposition to inhibition. In: The Psychology of Learning and Motivation. Vol. 43. San Diego, CA: B.H. Ross; 2003. pp. 163-214'},{id:"B31",body:'Smith R. Inhibition: History and Meaning in the Sciences of Mind and Brain. Berkeley: University of California Press; 1992'},{id:"B32",body:'Logan GD, Cowan WB, Davis KA. On the ability to inhibit simple and choice reaction time responses: A model and a method. Journal of Experimental Psychology. Human Perception and Performance. 1984;10(2):276-291'},{id:"B33",body:'Miyake A, Friedman NP, Emerson MJ, Witzki AH, Howerter A, Wager TD. The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: A latent variable analysis. Cognitive Psychology. 2000;41(1):49-100'},{id:"B34",body:'Miyake A, Friedman NP. The nature and organization of individual differences in executive functions: Four general conclusions. Current Directions in Psychological Science. 2012;21(1):8-14'},{id:"B35",body:'Botvinick M, Braver T. Motivation and cognitive control: From behavior to neural mechanism. Annual Review of Psychology. 2015;66:83-113'},{id:"B36",body:'Ridderinkhof KR. Neurocognitive mechanisms of perception-action coordination: A review and theoretical integration. Neuroscience and Biobehavioral Reviews. 2014;46(Pt 1):3-29'},{id:"B37",body:'Verbruggen F. Executive control of actions across time and space. Current Directions in Psychological Science. 2016;25(6):399-404'},{id:"B38",body:'Verbruggen F, Logan GD. Proactive adjustments of response strategies in the stop-signal paradigm. Journal of Experimental Psychology. Human Perception and Performance. 2009;35(3):835-854'},{id:"B39",body:'Friedman NP, Miyake A. The relations among inhibition and interference control functions: A latent-variable analysis. Journal of Experimental Psychology. General. 2004;133(1):101-135'},{id:"B40",body:'Pettigrew C, Martin RC. Cognitive declines in healthy aging: Evidence from multiple aspects of interference resolution. Psychology and Aging. 2014;29(2):187-204'},{id:"B41",body:'Rey-Mermet A, Gade M, Oberauer K. Should we stop thinking about inhibition? Searching for individual and age differences in inhibition ability. Journal of Experimental Psychology. Learning, Memory, and Cognition. 2018;44(4):501-526'},{id:"B42",body:'Stahl C, Voss A, Schmitz F, Nuszbaum M, Tüscher O, Lieb K, et al. Behavioral components of impulsivity. Journal of Experimental Psychology. General. 2014;143(2):850-886'},{id:"B43",body:'Aron AR. From reactive to proactive and selective control: Developing a richer model for stopping inappropriate responses. Biological Psychiatry. 2011;69(12):e55-e68'},{id:"B44",body:'Braver TS. The variable nature of cognitive control: A dual mechanisms framework. Trends in Cognitive Sciences. 2012;16(2):106-113'},{id:"B45",body:'Zandbelt BB, Bloemendaal M, Neggers SFW, Kahn RS, Vink M. Expectations and violations: Delineating the neural network of proactive inhibitory control. Human Brain Mapping. 2013;34(9):2015-2024'},{id:"B46",body:'Schall JD, Godlove DC. Current advances and pressing problems in studies of stopping. Current Opinion in Neurobiology. 2012;22(6):1012-1021'},{id:"B47",body:'Fillmore MT, Weafer J. Behavioral inhibition and addiction. In: MacKillop J, de Wit H, editors. The Wiley-Blackwell Handbook of Addiction Psychopharmacology. Chichester, West Sussex; Malden, MA: Wiley-Blackwell; 2013. pp. 135-164'},{id:"B48",body:'Verdejo-Garcia A, Chong TT-J, Stout JC, Yücel M, London ED. Stages of dysfunctional decision-making in addiction. Pharmacology, Biochemistry, and Behavior. 2018;164:99-105'},{id:"B49",body:'Billieux J, Gay P, Rochat L, Khazaal Y, Zullino D, Van der Linden M. Lack of inhibitory control predicts cigarette smoking dependence: Evidence from a non-deprived sample of light to moderate smokers. Drug and Alcohol Dependence. 2010;112(1-2):164-167'},{id:"B50",body:'Powell J, Dawkins L, West R, Powell J, Pickering A. Relapse to smoking during unaided cessation: Clinical, cognitive and motivational predictors. Psychopharmacology. 2010;212(4):537-549'},{id:"B51",body:'Noël X, Van der Linden M, Schmidt N, Sferrazza R, Hanak C, Le Bon O, et al. Supervisory attentional system in nonamnesic alcoholic men. Archives of General Psychiatry. 2001;58(12):1152-1158'},{id:"B52",body:'Noël X, Brevers D, Hanak C, Kornreich C, Verbanck P, Verbruggen F. On the automaticity of response inhibition in individuals with alcoholism. Journal of Behavior Therapy and Experimental Psychiatry. 2016;51:84-91'},{id:"B53",body:'Adams S, Mokrysz C, Attwood AS, Munafò MR. Resisting the urge to smoke: Inhibitory control training in cigarette smokers. Royal Society Open Science. 2017;4(8):170045'},{id:"B54",body:'Galimberti E, Martoni RM, Cavallini MC, Erzegovesi S, Bellodi L. Motor inhibition and cognitive flexibility in eating disorder subtypes. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2012;36(2):307-312'},{id:"B55",body:'Brevers D, Noël X. Pathological gambling and the loss of willpower: A neurocognitive perspective. Socioaffective Neuroscience & Psychology. 2013;3:21592'},{id:"B56",body:'Sharif-Razi M, Hodgins DC, Goghari VM. Reactive and proactive control mechanisms of response inhibition in gambling disorder. Psychiatry Research. 2019;272:114-121'},{id:"B57",body:'Czapla M, Simon JJ, Richter B, Kluge M, Friederich H-C, Herpertz S, et al. The impact of cognitive impairment and impulsivity on relapse of alcohol-dependent patients: Implications for psychotherapeutic treatment. Addiction Biology. 2016;21(4):873-884'},{id:"B58",body:'Goudriaan AE, Oosterlaan J, De Beurs E, Van Den Brink W. The role of self-reported impulsivity and reward sensitivity versus neurocognitive measures of disinhibition and decision-making in the prediction of relapse in pathological gamblers. Psychological Medicine. 2008;38(1):41-50'},{id:"B59",body:'Charles-Walsh K, Furlong L, Munro DG, Hester R. Inhibitory control dysfunction in nicotine dependence and the influence of short-term abstinence. Drug and Alcohol Dependence. 2014;143:81-86'},{id:"B60",body:'Smith JL, Mattick RP, Jamadar SD, Iredale JM. Deficits in behavioural inhibition in substance abuse and addiction: A meta-analysis. Drug and Alcohol Dependence. 2014;145C:1-33'},{id:"B61",body:'Otten R, Mun CJ, Shaw DS, Wilson MN, Dishion TJ. A developmental cascade model for early adolescent-onset substance use: The role of early childhood stress. Addiction. 2019;114(2):326-334'},{id:"B62",body:'Noël X, Bechara A, Dan B, Hanak C, Verbanck P. Response inhibition deficit is involved in poor decision making under risk in nonamnesic individuals with alcoholism. Neuropsychology. 2007;21(6):778-786'},{id:"B63",body:'Bechara A, Damasio H, Tranel D, Damasio AR. Deciding advantageously before knowing the advantageous strategy. Science. 1997;275(5304):1293-1295'},{id:"B64",body:'Bechara A. Risky business: Emotion, decision-making, and addiction. Journal of Gambling Studies. 2003;19(1):23-51'},{id:"B65",body:'Bechara A. The role of emotion in decision-making: Evidence from neurological patients with orbitofrontal damage. Brain and Cognition. 2004;55(1):30-40'},{id:"B66",body:'Verbruggen F, Adams R, Chambers CD. Proactive motor control reduces monetary risk taking in gambling. Psychological Science. 2012;23(7):805-815'},{id:"B67",body:'Verbruggen F, Adams RC, van’t Wout F, Stevens T, McLaren IPL, Chambers CD. Are the effects of response inhibition on gambling long-lasting? PLoS One. 2013;8(7):e70155'},{id:"B68",body:'Stevens T, Brevers D, Chambers CD, Lavric A, McLaren IPL, Mertens M, et al. How does response inhibition influence decision making when gambling? Journal of Experimental Psychology. Applied. 2015;21(1):15-36'},{id:"B69",body:'Stacy AW, Wiers RW. Implicit cognition and addiction: A tool for explaining paradoxical behavior. Annual Review of Clinical Psychology. 2010;6:551-575'},{id:"B70",body:'Houben K, Wiers RW. Response inhibition moderates the relationship between implicit associations and drinking behavior. Alcoholism, Clinical and Experimental Research. 2009;33(4):626-633'},{id:"B71",body:'Thush C, Wiers RW, Ames SL, Grenard JL, Sussman S, Stacy AW. Interactions between implicit and explicit cognition and working memory capacity in the prediction of alcohol use in at-risk adolescents. Drug and Alcohol Dependence. 2008;94(1-3):116-124'},{id:"B72",body:'Figner B, Knoch D, Johnson EJ, Krosch AR, Lisanby SH, Fehr E, et al. Lateral prefrontal cortex and self-control in intertemporal choice. Nature Neuroscience. 2010;13(5):538-539'},{id:"B73",body:'Kirby KN, Petry NM, Bickel WK. Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls. Journal of Experimental Psychology. General. 1999;128(1):78-87'},{id:"B74",body:'Amlung M, Vedelago L, Acker J, Balodis I, MacKillop J. Steep delay discounting and addictive behavior: A meta-analysis of continuous associations. Addiction. 2017;112(1):51-62'},{id:"B75",body:'Bickel WK, Koffarnus MN, Moody L, Wilson AG. The behavioral- and neuro-economic process of temporal discounting: A candidate behavioral marker of addiction. Neuropharmacology. 2014;76(Pt B):518-527'},{id:"B76",body:'Bjork JM, Momenan R, Hommer DW. Delay discounting correlates with proportional lateral frontal cortex volumes. Biological Psychiatry. 2009;65(8):710-713'},{id:"B77",body:'Jauregi A, Kessler K, Hassel S. Linking cognitive measures of response inhibition and reward sensitivity to trait impulsivity. Frontiers in Psychology. 2018;9:2306'},{id:"B78",body:'Solanto MV, Abikoff H, Sonuga-Barke E, Schachar R, Logan GD, Wigal T, et al. The ecological validity of delay aversion and response inhibition as measures of impulsivity in AD/HD: A supplement to the NIMH multimodal treatment study of AD/HD. Journal of Abnormal Child Psychology. 2001;29(3):215-228'},{id:"B79",body:'Verdejo-Garcia A. Cognitive training for substance use disorders: Neuroscientific mechanisms. Neuroscience and Biobehavioral Reviews. 2016;68:270-281'},{id:"B80",body:'Enge S, Behnke A, Fleischhauer M, Küttler L, Kliegel M, Strobel A. No evidence for true training and transfer effects after inhibitory control training in young healthy adults. Journal of Experimental Psychology. Learning, Memory, and Cognition. 2014;40(4):987-1001'},{id:"B81",body:'Jones A, Guerrieri R, Fernie G, Cole J, Goudie A, Field M. The effects of priming restrained versus disinhibited behaviour on alcohol-seeking in social drinkers. Drug and Alcohol Dependence. 2011;113(1):55-61'},{id:"B82",body:'Redick TS, Shipstead Z, Harrison TL, Hicks KL, Fried DE, Hambrick DZ, et al. No evidence of intelligence improvement after working memory training: A randomized, placebo-controlled study. Journal of Experimental Psychology. General. 2013;142(2):359-379'},{id:"B83",body:'Klingberg T. Training and plasticity of working memory. Trends in Cognitive Sciences. 2010;14(7):317-324'},{id:"B84",body:'Houben K, Wiers RW, Jansen A. Getting a grip on drinking behavior: Training working memory to reduce alcohol abuse. Psychological Science. 2011;22(7):968-975'},{id:"B85",body:'Wanmaker S, Leijdesdorff SMJ, Geraerts E, van de Wetering BJM, Renkema PJ, Franken IHA. The efficacy of a working memory training in substance use patients: A randomized double-blind placebo-controlled clinical trial. Journal of Clinical and Experimental Neuropsychology. 2018;40(5):473-486'},{id:"B86",body:'Alcorn JL, Pike E, Stoops WS, Lile JA, Rush CR. A pilot investigation of acute inhibitory control training in cocaine users. Drug and Alcohol Dependence. 2017;174:145-149'},{id:"B87",body:'Houben K, Havermans RC, Nederkoorn C, Jansen A. Beer à no-go: Learning to stop responding to alcohol cues reduces alcohol intake via reduced affective associations rather than increased response inhibition. Addiction. 2012;107(7):1280-1287'},{id:"B88",body:'Houben K, Jansen A. Training inhibitory control. A recipe for resisting sweet temptations. Appetite. 2011;56(2):345-349'},{id:"B89",body:'Jones A, Di Lemma LCG, Robinson E, Christiansen P, Nolan S, Tudur-Smith C, et al. Inhibitory control training for appetitive behaviour change: A meta-analytic investigation of mechanisms of action and moderators of effectiveness. Appetite. 2016;97:16-28'},{id:"B90",body:'Jones A, Field M. The effects of cue-specific inhibition training on alcohol consumption in heavy social drinkers. Experimental and Clinical Psychopharmacology. 2013;21(1):8-16'},{id:"B91",body:'Allom V, Mullan B, Hagger M. Does inhibitory control training improve health behaviour? A meta-analysis. Health Psychology Review. 2016;10(2):168-186'},{id:"B92",body:'Turton R, Bruidegom K, Cardi V, Hirsch CR, Treasure J. Novel methods to help develop healthier eating habits for eating and weight disorders: A systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews. 2016;61:132-155'},{id:"B93",body:'Eagle DM, Bari A, Robbins TW. The neuropsychopharmacology of action inhibition: Cross-species translation of the stop-signal and go/no-go tasks. Psychopharmacology. 2008;199(3):439-456'},{id:"B94",body:'Verbruggen F, Logan GD. Automatic and controlled response inhibition: Associative learning in the go/no-go and stop-signal paradigms. Journal of Experimental Psychology. General. 2008;137(4):649-672'},{id:"B95",body:'Adams RC, Lawrence NS, Verbruggen F, Chambers CD. Training response inhibition to reduce food consumption: Mechanisms, stimulus specificity and appropriate training protocols. Appetite. 2017;109:11-23'},{id:"B96",body:'Lawrence NS, Verbruggen F, Morrison S, Adams RC, Chambers CD. Stopping to food can reduce intake. Effects of stimulus-specificity and individual differences in dietary restraint. Appetite. 2015;85:91-103'},{id:"B97",body:'Lapenta OM, Sierve KD, de Macedo EC, Fregni F, Boggio PS. Transcranial direct current stimulation modulates ERP-indexed inhibitory control and reduces food consumption. Appetite. 2014;83:42-48'},{id:"B98",body:'Veling H, Aarts H, Papies EK. Using stop signals to inhibit chronic dieters’ responses toward palatable foods. Behaviour Research and Therapy. 2011;49(11):771-780'},{id:"B99",body:'Hare TA, Camerer CF, Rangel A. Self-control in decision-making involves modulation of the vmPFC valuation system. Science. New York, N.Y. 2009;324(5927):646-648'},{id:"B100",body:'Veling H, Aarts H, Stroebe W. Stop signals decrease choices for palatable foods through decreased food evaluation. Frontiers in Psychology. 2013;4:875'},{id:"B101",body:'Wessel JR, O’Doherty JP, Berkebile MM, Linderman D, Aron AR. Stimulus devaluation induced by stopping action. Journal of Experimental Psychology. General. 2014;143(6):2316-2329'},{id:"B102",body:'Friese M, Hofmann W, Wänke M. When impulses take over: Moderated predictive validity of explicit and implicit attitude measures in predicting food choice and consumption behaviour. The British Journal of Social Psychology. 2008;47(Pt 3):397-419'},{id:"B103",body:'Ferrey AE, Frischen A, Fenske MJ. Hot or not: Response inhibition reduces the hedonic value and motivational incentive of sexual stimuli. Frontiers in Psychology. 2012;3:575'},{id:"B104",body:'Lawrence NS, O’Sullivan J, Parslow D, Javaid M, Adams RC, Chambers CD, et al. Training response inhibition to food is associated with weight loss and reduced energy intake. Appetite. 2015;95:17-28'},{id:"B105",body:'Veling H, Holland RW, van Knippenberg A. When approach motivation and behavioral inhibition collide: Behavior regulation through stimulus devaluation. Journal of Experimental Social Psychology. 2008;44(4):1013-1019'},{id:"B106",body:'Eberl C, Wiers RW, Pawelczack S, Rinck M, Becker ES, Lindenmeyer J. Approach bias modification in alcohol dependence: Do clinical effects replicate and for whom does it work best? Developmental Cognitive Neuroscience. 2013;4:38-51'},{id:"B107",body:'Wiers RW, Eberl C, Rinck M, Becker ES, Lindenmeyer J. Retraining automatic action tendencies changes alcoholic patients’ approach bias for alcohol and improves treatment outcome. Psychological Science. 2011;22(4):490-497'},{id:"B108",body:'Cristea IA, Kok RN, Cuijpers P. The effectiveness of cognitive bias modification interventions for substance addictions: A meta-analysis. PLoS One. 2016;11(9):e0162226'},{id:"B109",body:'Wiers RW, Boffo M, Field M. What’s in a trial? On the importance of distinguishing between experimental lab studies and randomized controlled trials: The case of cognitive bias modification and alcohol use disorders. Journal of Studies on Alcohol and Drugs. 2018;79(3):333-343'},{id:"B110",body:'Boffo M, Pronk T, Wiers RW, Mannarini S. Combining cognitive bias modification training with motivational support in alcohol dependent outpatients: Study protocol for a randomised controlled trial. Trials. 2015;16:63'},{id:"B111",body:'Houben K, Havermans RC, Wiers RW. Learning to dislike alcohol: Conditioning negative implicit attitudes toward alcohol and its effect on drinking behavior. Psychopharmacology. 2010;211(1):79-86'},{id:"B112",body:'Freeman SM, Razhas I, Aron AR. Top-down response suppression mitigates action tendencies triggered by a motivating stimulus. Current Biology: CB. 2014;24(2):212-216'},{id:"B113",body:'Veling H, Aarts H, Stroebe W. Using stop signals to reduce impulsive choices for palatable unhealthy foods. British Journal of Health Psychology. 2013;18(2):354-368'},{id:"B114",body:'Rolland B, D’Hondt F, Montègue S, Brion M, Peyron E, D’Aviau de Ternay J, et al. A patient-tailored evidence-based approach for developing early neuropsychological training programs in addiction settings. Neuropsychology Review. 2019;29(1):103-115'},{id:"B115",body:'Kuhn J, Lenartz D, Huff W, Lee S, Koulousakis A, Klosterkoetter J, et al. Remission of alcohol dependency following deep brain stimulation of the nucleus accumbens: Valuable therapeutic implications? Journal of Neurology, Neurosurgery, and Psychiatry. 2007;78(10):1152-1153'},{id:"B116",body:'Levy D, Shabat-Simon M, Shalev U, Barnea-Ygael N, Cooper A, Zangen A. Repeated electrical stimulation of reward-related brain regions affects cocaine but not “natural” reinforcement. The Journal of Neuroscience. 2007;27(51):14179-14189'},{id:"B117",body:'Voges J, Waerzeggers Y, Maarouf M, Lehrke R, Koulousakis A, Lenartz D, et al. Deep-brain stimulation: Long-term analysis of complications caused by hardware and surgery—Experiences from a single centre. Journal of Neurology, Neurosurgery, and Psychiatry. 2006;77(7):868-872'},{id:"B118",body:'Wang TR, Moosa S, Dallapiazza RF, Elias WJ, Lynch WJ. Deep brain stimulation for the treatment of drug addiction. Neurosurgical Focus. 2018;45(2):E11'},{id:"B119",body:'Benabid AL, Pollak P, Louveau A, Henry S, de Rougemont J. Combined (thalamotomy and stimulation) stereotactic surgery of the VIM thalamic nucleus for bilateral Parkinson disease. Applied Neurophysiology. 1987;50(1-6):344-346'},{id:"B120",body:'Nuttin B, Cosyns P, Demeulemeester H, Gybels J, Meyerson B. Electrical stimulation in anterior limbs of internal capsules in patients with obsessive-compulsive disorder. The Lancet. 1999;354(9189):1526'},{id:"B121",body:'Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005;45(5):651-660'},{id:"B122",body:'Kuhn J, Bauer R, Pohl S, Lenartz D, Huff W, Kim EH, et al. Observations on unaided smoking cessation after deep brain stimulation of the nucleus accumbens. European Addiction Research. 2009;15(4):196-201'},{id:"B123",body:'Ardouin C, Voon V, Worbe Y, Abouazar N, Czernecki V, Hosseini H, et al. Pathological gambling in Parkinson’s disease improves on chronic subthalamic nucleus stimulation. Movement Disorders. 2006;21(11):1941-1946'},{id:"B124",body:'Luigjes J, Segrave R, de Joode N, Figee M, Denys D. Efficacy of invasive and non-invasive brain modulation interventions for addiction. Neuropsychology Review. 2018;29:116-138'},{id:"B125",body:'Sesia T, Bulthuis V, Tan S, Lim LW, Vlamings R, Blokland A, et al. Deep brain stimulation of the nucleus accumbens shell increases impulsive behavior and tissue levels of dopamine and serotonin. Experimental Neurology. 2010;225(2):302-309'},{id:"B126",body:'Sesia T, Temel Y, Lim LW, Blokland A, Steinbusch HWM, Visser-Vandewalle V. Deep brain stimulation of the nucleus accumbens core and shell: Opposite effects on impulsive action. Experimental Neurology. 2008;214(1):135-139'},{id:"B127",body:'Crews FT, Boettiger CA. Impulsivity, frontal lobes and risk for addiction. Pharmacology, Biochemistry, and Behavior. 2009;93(3):237-247'},{id:"B128",body:'Luigjes J, van den Brink W, Schuurman PR, Kuhn J, Denys D. Is deep brain stimulation a treatment option for addiction? Addiction. 2015;110(4):547-548'},{id:"B129",body:'Kekic M, Boysen E, Campbell IC, Schmidt U. A systematic review of the clinical efficacy of transcranial direct current stimulation (tDCS) in psychiatric disorders. Journal of Psychiatric Research. 2016;74:70-86'},{id:"B130",body:'Tortella G. Transcranial direct current stimulation in psychiatric disorders. World Journal of Psychiatry. 2015;5(1):88'},{id:"B131",body:'Jansen JM, Daams JG, Koeter MWJ, Veltman DJ, van den Brink W, Goudriaan AE. Effects of non-invasive neurostimulation on craving: A meta-analysis. Neuroscience & Biobehavioral Reviews. 2013;37(10):2472-2480'},{id:"B132",body:'Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, et al. Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology. 1997;48(5):1398-1403'},{id:"B133",body:'Siebner HR, Peller M, Willoch F, Minoshima S, Boecker H, Auer C, et al. Lasting cortical activation after repetitive TMS of the motor cortex: A glucose metabolic study. Neurology. 2000;54(4):956-963'},{id:"B134",body:'Maeda F, Keenan JP, Tormos JM, Topka H, Pascual-Leone A. Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability. Experimental Brain Research. 2000;133(4):425-430'},{id:"B135",body:'Deng Z-D, Lisanby SH, Peterchev AV. Electric field depth-focality tradeoff in transcranial magnetic stimulation: Simulation comparison of 50 coil designs. Brain Stimulation. 2013;6(1):1-13'},{id:"B136",body:'Amiaz R, Levy D, Vainiger D, Grunhaus L, Zangen A. Repeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumption. Addiction. 2009;104(4):653-660'},{id:"B137",body:'Trojak B, Meille V, Achab S, Lalanne L, Poquet H, Ponavoy E, et al. Transcranial magnetic stimulation combined with nicotine replacement therapy for smoking cessation: A randomized controlled trial. Brain Stimulation. 2015;8(6):1168-1174'},{id:"B138",body:'Ceccanti M, Inghilleri M, Attilia ML, Raccah R, Fiore M, Zangen A, et al. Deep TMS on alcoholics: Effects on cortisolemia and dopamine pathway modulation. A pilot study. Canadian Journal of Physiology and Pharmacology. 2015;93(4):283-290'},{id:"B139",body:'Bolloni C, Panella R, Pedetti M, Frascella AG, Gambelunghe C, Piccoli T, et al. Bilateral transcranial magnetic stimulation of the prefrontal cortex reduces cocaine intake: A pilot study. Frontiers in Psychiatry. 2016;7:133'},{id:"B140",body:'Höppner J, Broese T, Wendler L, Berger C, Thome J. Repetitive transcranial magnetic stimulation (rTMS) for treatment of alcohol dependence. The World Journal of Biological Psychiatry. 2011;12(Suppl 1):57-62'},{id:"B141",body:'Herremans SC, Vanderhasselt M-A, De Raedt R, Baeken C. Reduced intra-individual reaction time variability during a Go-NoGo task in detoxified alcohol-dependent patients after one right-sided dorsolateral prefrontal HF-rTMS session. Alcohol and Alcoholism (Oxford, Oxfordshire). 2013;48(5):552-557'},{id:"B142",body:'Steele JD, Lawrie SM. Segregation of cognitive and emotional function in the prefrontal cortex: A stereotactic meta-analysis. NeuroImage. 2004;21(3):868-875'},{id:"B143",body:'Naqvi NH, Rudrauf D, Damasio H, Bechara A. Damage to the insula disrupts addiction to cigarette smoking. Science. 2007;315(5811):531-534'},{id:"B144",body:'Volkow ND, Baler RD. NOW vs LATER brain circuits: Implications for obesity and addiction. Trends in Neurosciences. 2015;38(6):345-352'},{id:"B145",body:'Cho SS, Koshimori Y, Aminian K, Obeso I, Rusjan P, Lang AE, et al. Investing in the future: Stimulation of the medial prefrontal cortex reduces discounting of delayed rewards. Neuropsychopharmacology. 2015;40(3):546-553'},{id:"B146",body:'Zack M, Cho SS, Parlee J, Jacobs M, Li C, Boileau I, et al. Effects of high frequency repeated transcranial magnetic stimulation and continuous theta burst stimulation on gambling reinforcement, delay discounting, and stroop interference in men with pathological gambling. Brain Stimulation. 2016;9(6):867-875'},{id:"B147",body:'Huang Y-Z, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005;45(2):201-206'},{id:"B148",body:'Lowe CJ, Manocchio F, Safati AB, Hall PA. The effects of theta burst stimulation (TBS) targeting the prefrontal cortex on executive functioning: A systematic review and meta-analysis. Neuropsychologia. 2018;111:344-359'},{id:"B149",body:'Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. The Journal of Physiology. 2000;527(Pt 3):633-639'},{id:"B150",body:'Nitsche MA, Paulus W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology. 2001;57(10):1899-1901'},{id:"B151",body:'Woods AJ, Antal A, Bikson M, Boggio PS, Brunoni AR, Celnik P, et al. A technical guide to tDCS, and related non-invasive brain stimulation tools. Clinical Neurophysiology. 2016;127(2):1031-1048'},{id:"B152",body:'Boggio PS, Nunes A, Rigonatti SP, Nitsche MA, Pascual-Leone A, Fregni F. Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restorative Neurology and Neuroscience. 2007;25(2):123-129'},{id:"B153",body:'Strube W, Bunse T, Nitsche MA, Nikolaeva A, Palm U, Padberg F, et al. Bidirectional variability in motor cortex excitability modulation following 1 mA transcranial direct current stimulation in healthy participants. Physiological Reports. 2016;4(15):e12884'},{id:"B154",body:'Kang N, Kim RK, Kim HJ. Effects of transcranial direct current stimulation on symptoms of nicotine dependence: A systematic review and meta-analysis. Addictive Behaviors. 2019;96:133-139'},{id:"B155",body:'Sauvaget A, Trojak B, Bulteau S, Jiménez-Murcia S, Fernández-Aranda F, Wolz I, et al. Transcranial direct current stimulation (tDCS) in behavioral and food addiction: A systematic review of efficacy, technical, and methodological issues. Frontiers in Neuroscience. 2015;9:349'},{id:"B156",body:'Spagnolo PA, Goldman D. Neuromodulation interventions for addictive disorders: Challenges, promise, and roadmap for future research. Brain. 2017;140(5):1183-1203'},{id:"B157",body:'Russo R, Twyman P, Cooper NR, Fitzgerald PB, Wallace D. When you can, scale up: Large-scale study shows no effect of tDCS in an ambiguous risk-taking task. Neuropsychologia. 2017;104:133-143'},{id:"B158",body:'Skinner MD, Aubin H-J. Craving’s place in addiction theory: Contributions of the major models. Neuroscience and Biobehavioral Reviews. 2010;34(4):606-623'},{id:"B159",body:'Klauss J, Penido Pinheiro LC, Silva Merlo BL, Santos GAC, Fregni F, Nitsche MA, et al. A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence. The International Journal of Neuropsychopharmacology. 2014;17(11):1793-1803'},{id:"B160",body:'Falcone M, Bernardo L, Wileyto EP, Allenby C, Burke AM, Hamilton R, et al. Lack of effect of transcranial direct current stimulation (tDCS) on short-term smoking cessation: Results of a randomized, sham-controlled clinical trial. Drug and Alcohol Dependence. 2019;194:244-251'},{id:"B161",body:'Mondino M, Luck D, Grot S, Januel D, Suaud-Chagny M-F, Poulet E, et al. Effects of repeated transcranial direct current stimulation on smoking, craving and brain reactivity to smoking cues. Scientific Reports. 2018;8(1):8724'},{id:"B162",body:'Fregni F, Orsati F, Pedrosa W, Fecteau S, Tome FAM, Nitsche MA, et al. Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods. Appetite. 2008;51(1):34-41'},{id:"B163",body:'Goldman RL, Borckardt JJ, Frohman HA, O’Neil PM, Madan A, Campbell LK, et al. Prefrontal cortex transcranial direct current stimulation (tDCS) temporarily reduces food cravings and increases the self-reported ability to resist food in adults with frequent food craving. Appetite. 2011;56(3):741-746'},{id:"B164",body:'Kekic M, McClelland J, Campbell I, Nestler S, Rubia K, David AS, et al. The effects of prefrontal cortex transcranial direct current stimulation (tDCS) on food craving and temporal discounting in women with frequent food cravings. Appetite. 2014;78:55-62'},{id:"B165",body:'Montenegro RA, Okano AH, Cunha FA, Gurgel JL, Fontes EB, Farinatti PTV. Prefrontal cortex transcranial direct current stimulation associated with aerobic exercise change aspects of appetite sensation in overweight adults. Appetite. 2012;58(1):333-338'},{id:"B166",body:'Keeser D, Meindl T, Bor J, Palm U, Pogarell O, Mulert C, et al. Prefrontal transcranial direct current stimulation changes connectivity of resting-state networks during fMRI. The Journal of Neuroscience. 2011;31(43):15284-15293'},{id:"B167",body:'Meinzer M, Lindenberg R, Antonenko D, Flaisch T, Flöel A. Anodal transcranial direct current stimulation temporarily reverses age-associated cognitive decline and functional brain activity changes. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience. 2013;33(30):12470-12478'},{id:"B168",body:'Nelson JT, McKinley RA, Golob EJ, Warm JS, Parasuraman R. Enhancing vigilance in operators with prefrontal cortex transcranial direct current stimulation (tDCS). NeuroImage. 2014;85(Pt 3):909-917'},{id:"B169",body:'Brunoni AR, Vanderhasselt M-A. Working memory improvement with non-invasive brain stimulation of the dorsolateral prefrontal cortex: A systematic review and meta-analysis. Brain and Cognition. 2014;86:1-9'},{id:"B170",body:'Cunillera T, Brignani D, Cucurell D, Fuentemilla L, Miniussi C. The right inferior frontal cortex in response inhibition: A tDCS-ERP co-registration study. NeuroImage. 2016;140:66-75'},{id:"B171",body:'Yu J, Tseng P, Hung DL, Wu S-W, Juan C-H. Brain stimulation improves cognitive control by modulating medial-frontal activity and preSMA-vmPFC functional connectivity. Human Brain Mapping. 2015;36(10):4004-4015'},{id:"B172",body:'Campanella S, Schroder E, Monnart A, Vanderhasselt M-A, Duprat R, Rabijns M, et al. Transcranial direct current stimulation over the right frontal inferior cortex decreases neural activity needed to achieve inhibition: A double-blind ERP study in a male population. Clinical EEG and Neuroscience. 2017;48(3):176-188'},{id:"B173",body:'Petit G, Cimochowska A, Kornreich C, Hanak C, Verbanck P, Campanella S. Neurophysiological correlates of response inhibition predict relapse in detoxified alcoholic patients: Some preliminary evidence from event-related potentials. Neuropsychiatric Disease and Treatment. 2014;10:1025-1037'},{id:"B174",body:'Osimo SA, Korb S, Aiello M. Obesity, subliminal perception and inhibition: Neuromodulation of the prefrontal cortex. Behaviour Research and Therapy. 2019;119:103408'},{id:"B175",body:'Dickerson KC. Upregulating brain activity using non-drug reward imagery and real-time fMRI neurofeedback—A new treatment approach for addiction? eBioMedicine. 2018;38:21-22'},{id:"B176",body:'Orndorff-Plunkett F, Singh F, Aragón OR, Pineda JA. Assessing the effectiveness of neurofeedback training in the context of clinical and social neuroscience. Brain Sciences. 2017;7(8):95'},{id:"B177",body:'Thibault RT, Lifshitz M, Raz A. The self-regulating brain and neurofeedback: Experimental science and clinical promise. Cortex. 2016;74:247-261'},{id:"B178",body:'Cox WM, Subramanian L, Linden DEJ, Lührs M, McNamara R, Playle R, et al. Neurofeedback training for alcohol dependence versus treatment as usual: Study protocol for a randomized controlled trial. Trials. 2016;17(1):480'},{id:"B179",body:'deCharms RC. Applications of real-time fMRI. Nature Reviews Neuroscience. 2008;9(9):720-729'},{id:"B180",body:'Hanlon CA, Hartwell KJ, Canterberry M, Li X, Owens M, LeMatty T, et al. Reduction of cue-induced craving through realtime neurofeedback in nicotine users: The role of region of interest selection and multiple visits. Psychiatry Research: Neuroimaging. 2013;213(1):79-81'},{id:"B181",body:'Sitaram R, Ros T, Stoeckel L, Haller S, Scharnowski F, Lewis-Peacock J, et al. Closed-loop brain training: The science of neurofeedback. Nature Reviews Neuroscience. 2017;18(2):86-100'},{id:"B182",body:'Scott WC, Kaiser D, Othmer S, Sideroff SI. Effects of an EEG biofeedback protocol on a mixed substance abusing population. The American Journal of Drug and Alcohol Abuse. 2005;31(3):455-469'},{id:"B183",body:'Keith JR, Rapgay L, Theodore D, Schwartz JM, Ross JL. An assessment of an automated EEG biofeedback system for attention deficits in a substance use disorders residential treatment setting. Psychology of Addictive Behaviors. 2015;29(1):17-25'},{id:"B184",body:'Kober SE, Witte M, Stangl M, Väljamäe A, Neuper C, Wood G. Shutting down sensorimotor interference unblocks the networks for stimulus processing: An SMR neurofeedback training study. Clinical Neurophysiology. 2015;126(1):82-95'},{id:"B185",body:'Canterberry M, Hanlon CA, Hartwell KJ, Li X, Owens M, LeMatty T, et al. Sustained reduction of nicotine craving with real-time neurofeedback: Exploring the role of severity of dependence. Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco. 2013;15(12):2120-2124'},{id:"B186",body:'Karch S, Paolini M, Gschwendtner S, Jeanty H, Reckenfelderbäumer A, Yaseen O, et al. Real-time fMRI neurofeedback in patients with tobacco use disorder during smoking cessation: Functional differences and implications of the first training session in regard to future abstinence or relapse. Frontiers in Human Neuroscience. 2019;13:65'},{id:"B187",body:'Lapenta OM, Marques LM, Rego GG, Comfort WE, Boggio PS. tDCS in addiction and impulse control disorders. The Journal of ECT. 2018;34(3):182-192'},{id:"B188",body:'Sathappan AV, Luber BM, Lisanby SH. The dynamic duo: Combining noninvasive brain stimulation with cognitive interventions. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2019;89:347-360'},{id:"B189",body:'Rabey JM, Dobronevsky E, Aichenbaum S, Gonen O, Marton RG, Khaigrekht M. Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer’s disease: A randomized, double-blind study. Journal of Neural Transmission. 2013;120(5):813-819'},{id:"B190",body:'Segrave RA, Arnold S, Hoy K, Fitzgerald PB. Concurrent cognitive control training augments the antidepressant efficacy of tDCS: A pilot study. Brain Stimulation. 2014;7(2):325-331'},{id:"B191",body:'den Uyl TE, Gladwin TE, Wiers RW. Electrophysiological and behavioral effects of combined transcranial direct current stimulation and alcohol approach bias retraining in hazardous drinkers. Alcoholism, Clinical and Experimental Research. 2016;40(10):2124-2133'},{id:"B192",body:'den Uyl TE, Gladwin TE, Rinck M, Lindenmeyer J, Wiers RW. A clinical trial with combined transcranial direct current stimulation and alcohol approach bias retraining. Addiction Biology. 2017;22(6):1632-1640'},{id:"B193",body:'den Uyl TE, Gladwin TE, Lindenmeyer J, Wiers RW. A clinical trial with combined transcranial direct current stimulation and attentional bias modification in alcohol-dependent patients. Alcoholism, Clinical and Experimental Research. 2018;42(10):1961-1969'},{id:"B194",body:'Sedgmond J, Lawrence NS, Verbruggen F, Morrison S, Chambers CD, Adams RC. Prefrontal brain stimulation during food-related inhibition training: Effects on food craving, food consumption and inhibitory control. Royal Society Open Science. 2019;6(1):181186'},{id:"B195",body:'Claus ED, Klimaj SD, Chavez R, Martinez AD, Clark VP. A randomized trial of combined tDCS over right inferior frontal cortex and cognitive bias modification: Null effects on drinking and alcohol approach bias. Alcoholism, Clinical and Experimental Research. 2019;43(7):1591-1599'},{id:"B196",body:'Heeren A, Billieux J, Philippot P, De Raedt R, Baeken C, de Timary P, et al. Impact of transcranial direct current stimulation on attentional bias for threat: A proof-of-concept study among individuals with social anxiety disorder. Social Cognitive and Affective Neuroscience. 2017;12(2):251-260'},{id:"B197",body:'Carmi L, Tendler A, Bystritsky A, Hollander E, Blumberger DM, Daskalakis J, et al. Efficacy and safety of deep transcranial magnetic stimulation for obsessive-compulsive disorder: A prospective multicenter randomized double-blind placebo-controlled trial. The American Journal of Psychiatry.21 May 2019'},{id:"B198",body:'Carmi L, Alyagon U, Barnea-Ygael N, Zohar J, Dar R, Zangen A. Clinical and electrophysiological outcomes of deep TMS over the medial prefrontal and anterior cingulate cortices in OCD patients. Brain Stimulation. 2018;11(1):158-165'},{id:"B199",body:'Dinur-Klein L, Dannon P, Hadar A, Rosenberg O, Roth Y, Kotler M, et al. Smoking cessation induced by deep repetitive transcranial magnetic stimulation of the prefrontal and insular cortices: A prospective, randomized controlled trial. Biological Psychiatry. 2014;76(9):742-749'},{id:"B200",body:'Pavlov I. Conditioned Reflexes. USA: Oxford University Press; 1927'},{id:"B201",body:'Conklin CA, Tiffany ST. Applying extinction research and theory to cue-exposure addiction treatments. Addiction. 2002;97(2):155-167'},{id:"B202",body:'Dunsmoor JE, Niv Y, Daw N, Phelps EA. Rethinking extinction. Neuron. 2015;88(1):47-63'},{id:"B203",body:'Milton AL, Everitt BJ. The psychological and neurochemical mechanisms of drug memory reconsolidation: Implications for the treatment of addiction. The European Journal of Neuroscience. 2010;31(12):2308-2319'},{id:"B204",body:'Lee JLC, Nader K, Schiller D. An update on memory reconsolidation updating. Trends in Cognitive Sciences. 2017;21(7):531-545'},{id:"B205",body:'Nader K, Schafe GE, Le Doux JE. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature. 2000;406(6797):722-726'},{id:"B206",body:'Sandrini M, Cohen LG, Censor N. Modulating reconsolidation: A link to causal systems-level dynamics of human memories. Trends in Cognitive Sciences. 2015;19(8):475-482'},{id:"B207",body:'McGaugh JL. Time-dependent processes in memory storage. Science (New York, N.Y.). 1966;153(3742):1351-1358'},{id:"B208",body:'Soeter M, Kindt M. An abrupt transformation of phobic behavior after a post-retrieval amnesic agent. Biological Psychiatry. 2015;78(12):880-886'},{id:"B209",body:'Monfils M-H, Cowansage KK, Klann E, LeDoux JE. Extinction-reconsolidation boundaries: Key to persistent attenuation of fear memories. Science. 2009;324(5929):951-955'},{id:"B210",body:'Xue Y-X, Luo Y-X, Wu P, Shi H-S, Xue L-F, Chen C, et al. A memory retrieval-extinction procedure to prevent drug craving and relapse. Science (New York, N.Y.). 2012;336(6078):241-245'},{id:"B211",body:'Schiller D, Kanen JW, LeDoux JE, Monfils M-H, Phelps EA. Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement. Proceedings of the National Academy of Sciences of the United States of America. 2013;110(50):20040-20045'},{id:"B212",body:'Pedreira ME, Pérez-Cuesta LM, Maldonado H. Mismatch between what is expected and what actually occurs triggers memory reconsolidation or extinction. Learning & Memory (Cold Spring Harbor, N.Y.). 2004;11(5):579-585'},{id:"B213",body:'Sevenster D, Beckers T, Kindt M. Prediction error governs pharmacologically induced amnesia for learned fear. Science. 2013;339(6121):830-833'},{id:"B214",body:'Das RK, Lawn W, Kamboj SK. Rewriting the valuation and salience of alcohol-related stimuli via memory reconsolidation. Translational Psychiatry. 2015;5:e645'},{id:"B215",body:'Hon T, Das RK, Kamboj SK. The effects of cognitive reappraisal following retrieval-procedures designed to destabilize alcohol memories in high-risk drinkers. Psychopharmacology. 2016;233(5):851-861'},{id:"B216",body:'Kaag AM, Goudriaan AE, De Vries TJ, Pattij T, Wiers RW. A high working memory load prior to memory retrieval reduces craving in non-treatment seeking problem drinkers. Psychopharmacology. 2018;235(3):695-708'},{id:"B217",body:'Everitt BJ, Giuliano C, Belin D. Addictive behaviour in experimental animals: Prospects for translation. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 2018;373:1742'},{id:"B218",body:'Lane RD, Ryan L, Nadel L, Greenberg L. Memory reconsolidation, emotional arousal, and the process of change in psychotherapy: New insights from brain science. The Behavioral and Brain Sciences. 2015;38:e1'},{id:"B219",body:'Marián M, Szőllősi Á, Racsmány M. Anodal transcranial direct current stimulation of the right dorsolateral prefrontal cortex impairs long-term retention of reencountered memories. Cortex; A Journal Devoted to the Study of the Nervous System and Behavior. 2018;108:80-91'},{id:"B220",body:'Gladwin TE, Wiers CE, Wiers RW. Interventions aimed at automatic processes in addiction: Considering necessary conditions for efficacy. Current Opinion in Behavioral Sciences. 2017;13:19-24'},{id:"B221",body:'Connolly Gibbons MB, Crits-Christoph P, Barber JP, Stirman SW, Gallop R, Goldstein LA, et al. Unique and common mechanisms of change across cognitive and dynamic psychotherapies. Journal of Consulting and Clinical Psychology. 2009;77(5):801-813'},{id:"B222",body:'Connolly Gibbons MB, Crits-Christoph P, Barber JP, Schamberger M. Insight in psychotherapy: A review of empirical literature. In: Castonguay LG, Hill C, editors. Insight in Psychotherapy. 2007. pp. 143-165'},{id:"B223",body:'Gollwitzer P, Sheeran P. Implementation intentions and goal achievement: A meta-analysis of effects and processes. In: Zanna MP, editor. Advances in Experimental Social Psychology. Vol. 38. Academic Press; 2006. pp. 69-119'},{id:"B224",body:'Ekhtiari H, Tavakoli H, Addolorato G, Baeken C, Bonci A, Campanella S, et al. Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead. Neuroscience and Biobehavioral Reviews. 2019;104:118-140'},{id:"B225",body:'Campanella S, Schroder E, Kajosch H, Noel X, Kornreich C. Why cognitive event-related potentials (ERPs) should have a role in the management of alcohol disorders. Neuroscience and Biobehavioral Reviews. San Diego, California. 21 Jun 2018'},{id:"B226",body:'Dunbar AB, Taylor JR. Reconsolidation and psychopathology: Moving towards reconsolidation-based treatments. Neurobiology of Learning and Memory. 2017;142(Pt A):162-171'},{id:"B227",body:'Monfils MH, Holmes EA. Memory boundaries: Opening a window inspired by reconsolidation to treat anxiety, trauma-related, and addiction disorders. The Lancet. Psychiatry. 2018;5(12):1032-1042'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Xavier Noël",address:"xnoel@ulb.ac.be",affiliation:'
Psychological Medicine Laboratory, Faculty of Medicine, Université Libre de Bruxelles, Belgium
Psychological Medicine Laboratory, Faculty of Medicine, Université Libre de Bruxelles, Belgium
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1. Introduction
Following a meal, pancreatic β-cells produce insulin in response to increasing blood glucose and other metabolite levels for regulating systemic glucose homeostasis. Tissue insulin sensitivity, which characterizes the ability of a given concentration of insulin to correct blood glucose levels, is the driving force behind this homeostasis. Multiple processes in several organs are involved in this typically well-regulated homeostatic mechanism, including decreased glucose output from the liver (hepatic glucose output), increased glucose uptake into skeletal muscle and adipose tissue (where glucose is stored as glycogen), suppression of free fatty acid (FFA) release from adipocytes (suppression of lipolysis), and increased lipid accumulation in the liver and adipocytes. A sophisticated insulin-dependent signal transduction cascade controls these metabolic processes. Insulin resistance (IR) is defined as decreased insulin-stimulated glucose uptake into muscle and adipocytes and faulty insulin regulation of hepatic glucose production in patients with type 2 diabetes (T2D) and in many subjects affected by other conditions characterized by insulin resistance, such as obesity and polycystic ovary syndrome. The term insulin resistance was first coined to explain the considerable variability in the insulin dose necessary to lower high glucose levels in people with T2D, and then to characterize the magnitude of change in blood glucose level when a given amount of insulin and glucose was administered. The “defined quantity of insulin” is crucial because people with insulin resistance often have hyperinsulinemia, a condition in which insulin levels in the blood are higher than normal relative to the amount of blood glucose concentration under both fasting and fed conditions; this hyperinsulinemia compensates for IR in peripheral tissues to bring blood glucose levels back to normal [1].
When pancreas fails to supply excess insulin in humans with insulin resistance, a major defect in whole-body glucose homeostasis occurs, resulting in hyperglycemia and glucose intolerance (the latter including impaired fasting glucose and impaired glucose tolerance), which are the defining features of T2D. It is worth noting that, somewhat counterintuitively, patients with T2D frequently maintain “relative hyperinsulinemia” until the condition is at an advanced stage. IR is defined by insulin’s inability to induce glucose uptake into muscle and adipose cells due to a failure of the glucose transport mechanism mediated, at the molecular level, by glucose transporter type 4 (GLUT4) in those tissues. Furthermore, one of the hallmarks of IR is the inability to decrease hepatic glucose production, which is mostly due to a persistent increase in hepatic gluconeogenesis. IR has been linked to a variety of diseases. Indeed, IR represents a risk factor for various conditions, such as metabolic disorders (including T2D and obesity), heart disease, liver diseases (e.g., non-alcoholic fatty liver disease and non-alcoholic steatohepatitis), cancer, neurodegenerative diseases and frailty [2, 3, 4]. Despite the fact that IR is inextricably linked to T2D, an important factor involved in T2D pathophysiology is represented by the pancreas’ incapacity to function properly to compensate for the significant rise in blood glucose levels by secreting enough insulin to meet the increasing demand and help get blood glucose levels back to normal. IR is a key risk factor for T2D, yet it is not commonly recognized or treated in people without diabetes. The main reason for this phenomenon is that many people with insulin resistance do not have abnormal blood glucose levels. Therefore, diagnosis of IR is based on measuring insulin levels, which is not commonly done in clinical practice. Furthermore, only a small fraction of subjects with IR develop T2D, which is likely due to a propensity to β-cell failure in these subjects. There are no procedures to identify this susceptible subpopulation at this time. Individuals with IR are predisposed to significant disorders linked to T2D, including retinopathy, neuropathy and kidney disease, even if they do not have T2D [5]. In this chapter, the association between the early possible causes of IR is first discussed. Obesity is common in people with IR, but it is unclear whether concomitant hyperinsulinemia contributes to obesity development or whether it is a consequence of obesity-associated IR. We then look at how different metabolic tissues, such as muscle, adipose tissue, and the liver, communicate with one another. The mechanisms of impaired insulin signaling and the role of abnormal GLUT4 trafficking in the development of IR are also discussed. Extracellular factors that may contribute to IR are postulated. This discussion is then followed by a discussion of various intracellular molecular factors that contribute to IR. These factors have been considered as involved in processes that lead to IR. There are several ways for determining insulin action. Many laboratories have lately resorted to employing surrogate markers of insulin sensitivity and IR [6]. The “traditional” definition of IR is a condition in which blood glucose levels are abnormally high and insulin concentration needed to maintain glucose homeostasis is greater than predicted [7, 8].
2. Pathway to insulin resistance
Despite years of research, there is still a lot of uncertainty about the causative and temporal link between obesity, hyperinsulinemia, and IR. The proximal and distal parts of the insulin signaling system, which governs metabolism, can be arbitrarily partitioned. The classical components—which comprise the insulin receptor, insulin receptor substrate (IRS) proteins, phosphoinositide 3-kinase (PI3K) and AKT-constitute the proximal segment of the insulin signaling system. A common trait of the proximal components is their sparseness, which means that just a little part of each element is necessary to elicit a physiological signal. This guarantees signal amplification across the network. The proximal portion is also susceptible to very complex feedforward and feedback control, and is incorporated into a broader network that is dynamically regulated by combinatorial signaling inputs. The AKT substrates that are intimately related to the many physiological activities of insulin and are typically specialized to a particular cell type are referred to as the “distal segment” of the insulin signaling pathway. The distal elements are generally phosphorylated, which is a common trait. Insulin signaling begins with the hormone binding to its surface receptor, followed by activation of the receptor tyrosine kinase and tyrosine phosphorylation. IRS proteins are phosphorylated, causing them to create a signaling complex, which contains proteins with Src homology domains such as PI3K. As a result, phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3 or PIP3] is produced. Serine/threonine (Ser/Thr) protein kinases like PDK1 and AKT, for example, are recruited to the inner leaflet of the plasma membrane. AKT is phosphorylated by PDK1 at one of its phosphorylation sites. Partially phosphorylated AKT activates mTORC2, while phosphorylation of AKT specifically at Ser473 results in complete AKT activation. Thus, AKT is a critical node in the insulin signaling pathway. AKT performs a variety of biological roles and is involved in the majority, if not all, of physiological metabolic processes. The Rab GTPase-Activating Protein (GAP) is an AKT substrate, which activates TBC1D4 (TBC1 Domain Family Member 4), a protein that regulates GLUT4 trafficking within the plasma membrane. The activation of glucose transport by insulin is the key mechanism that is disrupted in insulin-resistant muscle and fat cells. The GLUT4 is a facilitative glucose transporter, which is found in skeletal muscle, heart, adipocytes, and insulin-responsive neurons; it regulates muscle/fat glucose transfer. Unlike other transporters (like GLUT1), GLUT4 has a set of specific trafficking cues that let it migrate from endosomes and the trans-Golgi network (TGN) to a special intracellular population of vesicles known as “GLUT4 storage vesicles” (GSVs) [9, 10, 11]. GSVs act as a distinct controlled exocytic compartment that distributes GLUT4 to the cell surface in response to insulin and serves as a storage depot assuring low rates of glucose absorption in the fasting state. Although exercise increases GLUT4 translocation in muscle cells, it does so through a different mechanism than that regulated by insulin. AKT plays a critical role in the insulin-regulated GLUT4 translocation [12, 13]. These characteristics typically coexist, and there is strong evidence that each can cause the other two branches of the triad to emerge: obesity, hyperinsulinemia, and IR are caused by overnutrition in humans and animals; in humans, IR and obesity may also be caused by continuous insulin administration or by genetic factors; in addition, IR in humans may be caused by pharmacological interventions resulting in hyperinsulinemia [14, 15].
3. The trio-axis of obesity-hyperinsulinemia-insulin resistance
Obesity and IR are two topics that come up frequently. The long period during which obesity, IR and hyperinsulinemia develop, makes the determination of causative links between these conditions (which usually coexist in most persons with T2D at the time of diagnosis) particularly difficult. Obesity is common in people with IR, although it is unclear whether simultaneous hyperinsulinemia plays a role in obesity development or it is predominantly a result of obesity-dependent IR [16]. The study of first-degree relatives of people with T2D who only show some of these traits has shown to be one of the most effective strategies for addressing some unanswered questions in humans. As a result, a trait seen in relatives is more likely to appear early in the course of the disease. It has been found that these subjects can have considerable IR in skeletal muscle and liver (and possibly fat), along with modest hyperinsulinemia, even if they are not obese or glucose-intolerant [15, 17, 18]. Individuals who are lean and glucose-tolerant but exhibit IR have been identified in larger cross-sectional studies [19]. In these instances, obesity is unlikely to be the primary cause of tissue IR. However, the term “obesity” is defined differently depending on race and genetic background, and it should therefore used with caution. Body mass index may be more important in determining the risk of IR. Body weight, in general, and visceral fat (but not subcutaneous fat), in particular, should be considered for evaluation [20].
First-degree relatives of people with T2D had greater levels of circulating FFAs and intramuscular lipids than healthy control subjects [21], suggesting that intramyocellular lipid content represents an early abnormality in the pathogenesis of insulin resistance and that it may contribute to the impaired glucose uptake in skeletal muscle of insulin-resistant subjects to a greater extent than overall adiposity. This is in line with severe IR observed in patients with lipodystrophy syndromes, which are a heterogeneous group of diseases characterized by selective absence of adipose tissue, loss of functional adipocytes, ectopic steatosis, and severe dyslipidemia and IR [22, 23]. On the other hand, individuals with moderate or severe obesity can be “metabolically healthy” [24]. While it appears acceptable, based on this research, to conclude that obesity is not a risk factor essential for the development of IR, it is vital to highlight that the majority of subjects with IR are obese. As we will discuss later in the text, the amount and location of adiposity required to create IR varies greatly between subjects.
4. Insulin resistance and hyperinsulinemia
Defining the temporal link between hyperinsulinemia and IR is difficult since, as far as we know, IR does not exist in the absence of hyperinsulinemia in humans, and vice versa. Hyperinsulinemia can produce obesity and IR in humans, as evidenced by trials in which insulin is administered to induce hyperinsulinemia in otherwise healthy individuals or as it occurs naturally in people with insulinomas [25, 26]. Transgenic expression of multiple copies of the normal insulin gene causes hyperinsulinemia in mice, resulting in IR and glucose intolerance [27]. Inhibition of insulin secretion has also been shown to improve insulin sensitivity and to decrease body weight in rodents [28, 29, 30]. In mice, deletion of one copy of the insulin gene resulted in a reduction of the Western diet-induced hyperinsulinemia and in an improvement of insulin sensitivity [31]. Overall, the hypotheses that hyperinsulinemia causes IR and promotes obesity, or that IR associated with obesity causes hyperinsulinemia, both remain acceptable for the initial events involved in T2D pathophysiology. In actuality, IR and hyperinsulinemia coexist and lead to T2D in almost all cases [32]. Several data suggest a concept in which hyperinsulinemia is responsible for, or at least partly contributes to, many of the negative effects of IR; this implies that IR is a state in which many of the insulin actions are preserved, a condition known as “selective IR” [33, 34, 35]. This was first observed in the liver, where increased insulin levels are unable to decrease hepatic glucose output in people with T2D, although lipogenesis (a canonical insulin action in the liver) remains elevated [36, 37]. One explanation for this selectivity is that insulin signaling pathway in the liver splits into two arms, with IR affecting only the arm regulating hepatic gluconeogenesis but not the arm regulating lipid metabolism. Hepatic de novo lipogenesis is essentially a cell-autonomous phenomenon, whereas cell-nonautonomous suppression of hepatic glucose production by insulin depends upon the insulin-mediated decrease of adipocyte lipolysis and circulating FFAs [38]. There has also been evidence of selective IR in muscle and adipose tissue. Those insulin-regulated activities which are not affected by IR—such as lipogenesis, protein synthesis, or transcriptional control mediated by FOXO proteins—are hyperactivated in the context of hyperinsulinemia and are likely to worsen IR or its consequences [33, 34, 39, 40].
5. Heterogeneity in the development of insulin resistance and progression of metabolic disease and T2D
T2D patients are divided into different phenotypic clusters based on their symptoms and clinical features. Individuals in one of these groups share phenotypic traits. As a result, performing a comprehensive analysis of these groups will be of great importance in clinical settings. Phenotype data analysis and combination of phenotype data with genetic data are essential to gain a better understanding of the variability in the development and presentation of IR in humans [10, 11, 41].
6. Tissue-specific progression to insulin resistance
The appearance of IR occurs in various tissues in a specific order. The development of IR in several tissues—including skeletal muscle, liver, and adipose tissue—is a hallmark of fully developed T2D in humans [18, 19, 39, 40, 42]. Evidence shows a hierarchical progression of IR in skeletal muscle, liver and adipose tissue, whereby IR develops in one tissue and then spreads to other tissues via systemic circulating components. For example, IR in the liver and adipose tissue appears to occur prior to IR in muscle in C57Bl/6 mice fed a high-fat diet [43, 44, 45, 46]. An equivalent pattern in humans is unlikely, since first-degree relatives of persons with T2D who are in the early stages of the disease already have IR in both muscle and liver (and possibly fat) [47]. Since insulin sensitivity in humans is often measured as whole-body glucose consumption (to which adipose tissue contributes only to a small extent), the temporal development of IR in adipose tissue in humans is less obvious. Interestingly, multiple investigations show that insulin modulates hepatic glucose production via reducing adipocyte lipolysis in a non-cell-autonomous manner [45]. Given these findings, it is reasonable to believe that adipose tissue IR is a precursor to metabolic disease and T2D. However, there is a clear distinction between insulin action on the liver and insulin action on muscle: even in people with T2D, the defect in insulin sensitivity in the liver can be almost completely overcome by sufficiently high levels of insulin, whereas muscle (and fat) insulin sensitivity defects persist at higher insulin concentrations [40, 48, 49]. This indicates that the processes that cause IR in muscle and liver are distinct.
Tissue-specific insulin receptor gene knockouts in mice have provided persuasive evidence that IR in a particular tissue can at least spread to other organs. Experimenting with a specific deficiency in insulin action in muscle, fat, or liver has resulted in the spread of IR to other tissues in a number of cases [50]. However, depending on the tissue that is first targeted and/or in which a specific gene deletion occurs, the mechanism of inter-tissue communication varies. The deletion of GLUT4, which is essential for glucose uptake in adipose tissue and skeletal muscle, is one of the best examples of this inter-tissue communication. In mice, deletion of GLUT4 resulted in IR not only in the tissue from which the transporter was removed, but also in all metabolic tissues, including the liver. Surprisingly, normalization of blood glucose levels reverses IR in the liver and adipose tissue in muscle-specific Glut4 gene-knockout mice. This shows that glucotoxicity generated IR in this animal model, which is not the case in many other IR models, including the Western diet-fed C57BL/6J mice, which do not show considerable hyperglycemia [48, 49, 50, 51]. As a result, while these animal studies have been useful in uncovering mechanisms of IR in specific tissues, their clinical applicability is less evident because complete deletion of a gene preferentially in one tissue does not occur in humans. Nonetheless, these experiments have provided persuasive evidence that metabolic or signaling changes in one tissue can have systemic effects by influencing insulin activity in other organs, a phenomenon that has been well-validated by clinical findings [50, 51].
7. Impaired insulin signaling in insulin resistance
Over the past 40 years, much research has resulted in a precise understanding of the insulin signaling system, which mediates the insulin’s physiological activities. One popular theory is that IR is caused by a defect in one or more of these signaling components. Another viewpoint is that IR is only caused by a shift in metabolic flux. For example, since the 1960s fatty acids have been proven to impede cells’ ability to utilize carbohydrate by allosterically modifying crucial rate-limiting steps in carbohydrate metabolic pathways. Several pieces of evidence, however, refute this claim. IR can be seen in cells or tissues long after the animal tissues have been removed, implying that changes that contribute to IR are long-lasting and cannot be explained by the acute action of a systemic factor. Fatty acids decrease the insulin-dependent translocation of GLUT4 to the plasma membrane and limit glucose uptake, there is no indication that this inhibition is caused by an allosteric change of GLUT4. Finally, IR can persist even after significant changes in dietary intake and after changes in metabolic state induced by pharmacological interventions. Thus, based on this information, it is reasonable to believe that IR is caused by an alteration in insulin signaling, although the exact location of the defect in the insulin signaling pathway remains unknown. Many essential components of the insulin signaling system have been identified. These components are divided into two parts: (i) the proximal part, which represents the core canonical signaling pathway, which includes the insulin receptor, IRS, PI3K and AKT; and (ii) the distal part, which includes TBC1D4, GSK3 (glycogen synthase kinase-3) and PDE3B (phosphodiesterase 3B). IR has been linked to defects in proximal insulin signaling system, that are associated with cellular stress. Many of the intracellular stressors discussed in the next sections activate a variety of intracellular Ser/Thr kinases, including novel PKCs (protein kinase C), JNK (c-Jun amino-terminal kinase), mTOR (mammalian target of rapamycin)and S6 kinase, which phosphorylate either the insulin receptor or the insulin receptor-related protein (INSRR). This could be a negative-feedback route that inhibits insulin signaling, according to the theory. However, as it will be discussed later, mounting evidence suggests that proximal insulin signaling system is unaffected in IR, implying that IR is caused by abnormalities in distal components of the insulin signaling network [52, 53, 54].
8. Insulin resistance and insulin signaling at the proximal level
The current focus on proximal insulin signaling abnormalities as a cause of IR stems from research into rare, monogenic severe types of IR that were discovered to be caused by mutations in the insulin receptor gene or by the development of insulin receptor blocking antibodies. Because of the superficial parallels between these rare conditions and T2D, it is reasonable to conclude that both diseases are caused by abnormalities in insulin receptor function, with the degree of receptor failure varying only slightly. Despite early enthusiasm for this theory, subsequent research found that IR in most forms of T2D was caused by neither impaired insulin receptor activity nor changes in the expression or quantity of insulin receptors. Insulin-binding experiments in rat adipocytes found that only 2.4% of total insulin receptors are required for a full biological response, implying that metabolic cells like muscle, fat and liver cells have an abundance of insulin receptors; this finding became known as the “spare insulin receptor” hypothesis. Insulin-mediated glucose uptake is reduced in insulin-resistant skeletal muscle cells and adipocytes. Since a slight decrease in the number of insulin receptors could only diminish insulin sensitivity and not the maximal insulin response [54, 55, 56, 57, 58]. While some studies contradict the “spare insulin receptor” hypothesis, recent genetic studies in mice support the idea that insulin signaling is preserved when the number of insulin receptors is reduced: mice with heterozygous loss of the insulin receptor had normal glucose and insulin tolerance and no impairment in AKT signaling in muscle or adipose tissue [59, 60, 61, 62].
The concept of spare insulin receptors shifted focus to a “postreceptor defect”, which is represented by defects in signaling downstream intermediates of the insulin receptor as the cause of IR [57, 58, 63]. Loss-of-function mutations in a number of signaling genes—including TBC1D4, AKT2, and IRS1 in humans—have been linked to severe forms of IR and T2D; moreover, cancer treatments that block PI3K or AKT have been linked to IR and T2D in humans. IR is caused in mice by targeted deletion of these genes. In addition, IR results in reduction of skeletal muscle AKT phosphorylation in response to insulin stimulation [34, 64, 65].
Given evidence of “spareness” for IRS, PI3K and AKT, the possibility that abnormalities in proximal insulin signaling might be responsible for IR has to be questioned, in the same way that the “spare receptor” theory has to be questioned. Homozygous deletion of AKT2, the most prevalent AKT gene isoform, resulted in a 90% reduction in insulin-stimulated AKT phosphorylation, but with no discernible defect in phosphorylation of the AKT substrate, or protein synthesis in response to insulin. In this situation, there was a tiny quantity of AKT1 expression that was not influenced by the gene deletion and was enough to deliver a completely functional message as response to insulin [66, 67]. Similarly, whereas AKT2 accounts for 85% of total AKT in the liver, its ablation does not result in significant glucose intolerance because the remaining AKT1 compensates for this defect [68]. The insulin dose-response curve in adipocytes, where the curve for AKT phosphorylation is “shifted to the right” compared to that for AKT substrate phosphorylation or insulin action, indicates that partial phosphorylation of AKT is sufficient for maximal biological responses, providing additional evidence for “spareness” in proximal insulin signaling network. At “normal” insulin concentrations, phosphorylation of AKT substrates requires only 1% of the entire AKT pool to be activated [69, 70, 71]. Furthermore, AKT phosphorylation is reduced in muscle from T2D patients, while downstream substrate phosphorylation is unaffected. Importantly, studies in animals fed a Western diet have indicated that IR begins before any detectable insulin signaling defect. Only 42 days of Western diet feeding resulted in reduced insulin-stimulated AKT phosphorylation, but TBC1D4 phosphorylation remained normal. As a result, minor changes in phosphorylation of proximal insulin signaling components may result in insulin sensitivity, but they are unlikely to result in a reduction in the maximal physiologic response [53].
Thus, how can the predominance of abnormalities in proximal insulin signaling components observed in diverse IR models, such as lower AKT phosphorylation, be reconciled? It is possible that these defects are a result of defective glucose metabolism rather than the cause. This could be a direct effect secondary to compensatory hyperinsulinemia, a typical hallmark of IR (since persistent hyperinsulinemia can lead to degradation of proximal insulin signaling components); alternatively, it may be a cell-autonomous effect due to a reduction in AKT phosphorylation as a result of defective glycolysis. Many studies used insulin-stimulated AKT phosphorylation in mice (sometimes in response to a maximal, pharmacological dosage of insulin) as an indicator of insulin sensitivity [72, 73, 74, 75].
However, under physiological settings such as the response to a meal (with minimal insulin release), AKT phosphorylation is barely detectable, due to the non-linearity between AKT phosphorylation and phosphorylation of its substrates. As a result, when evaluating the physiological importance of insulin signaling, it is critical to look at the phosphorylation of a variety of AKT substrates to determine if there is a major deficiency in “AKT activity” in vivo. These findings suggest that a minor impairment in proximal insulin signaling network is unlikely to account for the significant reduction in insulin-stimulated glucose uptake observed in patients with T2D. Furthermore, these findings underline that lower AKT2 phosphorylation should not be used as a direct marker or even as a proxy measure of IR [71].
Negative feedback loops originating from Ser/Thr kinases that phosphorylate and limit the action of IRS proteins have also been proposed as a cause of IR. This theory is refuted by a number of studies. Since Platelet-derived growth factor (PDGF) by-passes these proteins to activate glucose uptake, mice bred to overexpress PDGF receptor (PDGFR) in muscle presented an ideal model to explore whether deficiencies in insulin receptor or IRS were implicated in experimental IR. In these mice, PDGF treatment resulted in increased glucose uptake in muscle [76]. Notably, when PDGFR transgenic rats were fed a Western diet, muscle glucose uptake in response to PDGF was decreased to the same degree as insulin-mediated uptake. This refutes a role for inhibitory Ser/Thr phosphorylation of the insulin receptor or IRS as a cause of IR, indicating that the deficiency in glucose uptake or IR does not involve the insulin receptor or IRS [8, 53, 54, 77, 78].
Furthermore, in mice, targeted mutation of one of the major putative inhibitory sites in IRS1 (Ser307), deletion of potential mediators of IR, such as PKC (which is reported to phosphorylate insulin receptor), and pharmacological blockade of key negative feedback pathways, such as mTOR (which is activated by insulin signaling and inhibits signaling by phosphorylating IRS through a negative feedback mechanism) [78, 79, 80, 81].
Finally, investigations in humans with IR or T2D revealed that insulin-stimulated muscle glucose uptake is reduced by 50–100% even at maximum insulin dosages [82, 83, 84, 85], with no change or reduction in AKT phosphorylation [86, 87, 88]. Only a few of these studies addressed the mechanism of AKT substrate phosphorylation in depth, and those that did found no deficiency or poorly linked with IR. These findings support the theory that the proximal insulin signaling network in human tissues has enough “spareness” to overcome even a moderate deficiency in AKT phosphorylation [87, 88, 89], and that lowered AKT phosphorylation is adequate to ensure a normal signal transduction. As previously stated, faulty proximal insulin signaling is most likely a result of IR rather than a cause of IR [90].
9. GLUT4 and insulin resistance
Insulin stimulates the transfer of intracellular GLUT4 storage vesicles to the cell surface, resulting in glucose uptake in skeletal muscle cells and adipocytes (Figure 1) [91, 92, 93, 94]. Insulin-dependent GLUT4 translocation has been linked to IR in both skeletal muscle and adipose tissue. This decrease in GLUT4 availability at the plasma membrane causes a reduced glucose uptake, which can lead to other IR-related consequences like reduced AKT phosphorylation, protein synthesis defects, and increased lipolysis [72, 95, 96]. GLUT4 does not show spareness, unlike proximal insulin signaling components such as IRS1 and AKT. The fact that heterozygous GLUT4 gene-knockout mice acquire metabolic disease exemplifies this concept [97].
Figure 1.
Translocation of glucose transporter type 4 (GLUT4) from GLUT4 storage vesicles (GSVs) to the plasma membrane of normal adipocytes and skeletal muscle cells (a). This process is altered in conditions characterized by insulin resistance (b).
However, while GLUT4 levels are lowered by 50% in human adipose tissue from patients with T2D, such levels remain unaltered in skeletal muscle, implying that GLUT4 levels cannot explain IR development in skeletal muscle [98]. Despite normal GLUT4 levels, insulin-stimulated GLUT4 translocation to the cell surface in skeletal muscle is faulty in both individuals with T2D [92] and in several rodent models of IR [99, 100]. Importantly, while exercise-modulated GLUT4 translocation to the cell surface is unaffected [101], the impairment in muscle GLUT4 trafficking in T2D is insulin signaling-specific. Insulin and exercise both cause GLUT4 translocation to the cell surface from discrete intracellular compartments [102].
The ultimate defect that defines IR is the impaired GLUT4 translocation to the plasma membrane. However, it is unknown how the numerous potential intracellular IR mediators mentioned later affect GLUT4 trafficking. Three options are discussed here. First, GLUT4 translocation requires that GLUT4 is localized in the appropriate intracellular compartment, the so-called GLUT4 storage vesicles (GSVs); GLUT4 targeting to GLUT4 GSVs has been hypothesized to be altered in IR [91, 100]. However, whereas this would likely result in GLUT4 degradation, GLUT4 levels in skeletal muscle from patients with IR remain unaffected. Second, given the importance of protein phosphorylation in insulin action [101, 102, 103, 104], it is possible that the defect is caused by a distal component of the insulin-regulated phosphorylation network such as TBC1D4, which regulates GLUT4 trafficking, although there is no convincing evidence for defective TBC1D4 phosphorylation in IR [105]. TBC1D4 is unlikely to be the only AKT target causing GLUT4 translocation, as cells lacking TBC1D4 still have some insulin-sensitive glucose transport [106]. Recent phosphoproteomics studies have revealed the existence of a wide range of insulin-responsive phosphoproteins in metabolic cells, allowing for the identification of insulin signaling targets in the distal part of the insulin signaling pathway that may be involved in the development of IR [104]. Indeed, IR is associated with massive alterations in the architecture of the entire insulin signaling pathway, according to examination of muscle cells from T2D patients [107]. Finally, a direct alteration of GLUT4 or a defect in a yet undiscovered protein that interacts with GLUT4 could cause the abnormalities in GLUT4 trafficking. This could include carbonylation and oxidation-induced inactivation of GLUT4, which have been observed in humans as a response to short-term overnutrition [108]. Protein carbonylation is linked to H2O2 production, lipid peroxidation and IR, suggesting a link between such molecular processes and the development of IR [109].
10. Adipose tissue and insulin resistance
While IR is regularly seen in lean first-degree relatives of patients with T2D, it is also found in many lean “healthy” individuals, suggesting that IR is more common than previously thought. In this regard, dietary habits, physical activity level and genetics are important factors that can significantly contribute to IR. Adipose tissue makes a significant contribution to the development of IR. Limitations in peripheral adipose tissue storage capacity and expansion in response to over nutrition (as it occurs in overweight and obesity) lead to increased circulating lipids, subsequent lipid accumulation in non-adipose tissues (ectopic lipid in liver, skeletal muscle, heart, and pancreas) and development of lipid-induced IR and metabolic derangements [110, 111]. Because of this, and since there is a clear link between IR and increased adipose tissue mass, we will discuss the role of adipose tissue mass and lipotoxicity as significant drivers of IR, as well as the emerging mechanisms by which adipocytes contribute to systemic IR.
10.1 Adipose tissue dysfunction
IR in adipocytes could be the first step in the progression of adipose tissue dysfunction, similar to IR in muscle and liver. In adipocytes from first-degree relatives of patients with T2D, there is a low expression of markers of insulin sensitivity such as GLUT4 and adiponectin (a crucial systemic insulin-sensitizing adipokine produced by adipose tissue), supporting this theory [112]. Furthermore, adipocyte hypertrophy (increase in adipocyte size) appears to precede T2D onset in Pima Indians, a group of Native Americans with a high incidence of IR and T2D [113]. Additionally, mouse models with adipose-specific IR also have IR in their muscle and liver. Notably, IR in the muscle of adipose-specific Glut4 gene-knockout mice was only present in vivo but not when muscles were isolated and assessed in vitro, implying a role for systemic factors (which did not include circulating FFAs or inflammatory cytokines) in the progression of IR from adipose tissue-specific pathology [114, 115].
Human genetic research has also suggested that adipose tissue plays a significant role in IR. Studies in identical twins or first-degree relatives of T2D patients have shown that inheritance has a substantial influence in IR and T2D [116]. More than 250 genetic loci have been linked to T2D so far, however they only account for 25% of T2D heritability [117]. While these investigations have generally discovered genes linked to beta-cell function and insulin secretion, deeper analysis of phenotypes more closely aligned with IR have begun to uncover genetic drivers of IR in other organs. Surprisingly, several of these drivers are involved in the function of adipose tissue [118]. Although subclinical lipodystrophy is a rare cause of severe IR, it has been suggested that milder forms of lipodystrophy are responsible for IR in general, supporting a model in which excessive lipid spillover into circulation is a proximal, mechanistic cause of altered insulin action. Specifically, when the individual’s capacity to store lipids in adipose tissue has been exceeded, lipid spillover into circulation leads to elevated plasma FFAs and triglyceride levels, which result in increased ectopic storage of these molecules in non-adipose tissues—such as liver and skeletal muscle—and subsequent metabolic derangements via lipotoxicity (lipid-induced toxicity). Surprisingly, genes in the insulin signaling system linked to IR (IRS1 and GRB14) are also linked to familial partial lipodystrophy [119].
PPARG (Peroxisome Proliferator-Activated Receptor Gamma, a master positive regulator of adipogenesis) and CCDC92, DNAH10, and L3MBTL3 (regulators of adipocyte differentiation) were among the 53 loci discovered in a study employing an integrated genomic approach to find genes related to IR. Thiazolidinediones are insulin-sensitizing peroxisome proliferator-activated receptor gamma agonists that are used in the treatment of T2D and act by promoting adipogenesis and adipose tissue growth (through cell size and cell number increase or adipocyte hypertrophy and hyperplasia) [119]. The availability of additional lipid storage induced by thiazolidinediones may therefore promote insulin sensitivity by alleviating lipotoxicity [120]. These drugs also improve insulin sensitivity in first-degree relatives of T2D patients, implying that adipose tissue hypertrophy and “unhealthy” lipid storage are critical regulators of insulin action and contributors to IR [121].
Adipose tissue’s primary function is to store fat and release it into circulation when needed, and it has the unique capacity to expand in response to nutrient overload. Lipids can be released into the bloodstream when the adipocyte capacity to store lipids has been exceeded [39]. There is compelling evidence that the accumulation of excess lipids in non-adipose tissues (e.g., skeletal muscle and liver), known as lipotoxicity (a.k.a. lipid-induced toxicity), plays a role in the development of muscle and liver IR [122]. As a result, studies aimed at understanding the cause and magnitude of increased circulating lipid levels in IR are now being pursued. Furthermore, intracellular lipid accumulation in cells and tissues—including pancreatic beta cells and liver—has been linked to the onset of cellular dysfunctions, such as secretory abnormalities and inflammation (Figure 2). Elevated circulating FFA levels have been linked to IR, and this has been proposed as a possible cause of lipotoxicity [123].
Figure 2.
Excessive adipocyte lipid storage in response to overnutrition, resulting in adipocyte hypertrophy, inflammation and increased release of free fatty acids (FFAs) into circulation, leading to ectopic fat accumulation, lipotoxicity and development of insulin resistance in non-adipose tissues, such as liver and skeletal muscle.
In humans and animals, lipid infusion causes muscle IR and enhanced hepatic gluconeogenesis, the latter attributable to changes in metabolic fluxes rather than to fat accumulation [123, 124, 125]. Furthermore, animals with increased circulating FFA levels due to increased lipolysis develop muscle and hepatic IR, whereas obese mice with reduced fat cell lipolysis are protected from glucose intolerance [126]. It is worth noting that, as discussed elsewhere [127], circulating FFA levels in patients with IR or T2D usually are not elevated. However, there are several confounders in this measurement, including the wide range of FFA levels in healthy adults and the fact that fasting FFAs are typically assessed rather than the more relevant postprandial FFAs. Nonetheless, there is strong evidence that serum FFA levels are elevated in first-degree relatives of patients with T2D [127, 128], implying that this elevation represents an early stage of the disease. It is unclear if the rise in circulating FFA levels is related to defects in insulin-mediated regulation of lipolysis, to alterations in fat storage capacity, or to an increase in adipose tissue mass without defects in lipolysis. Lipolysis per gram of adipose tissue mass is considerably lower in obese subjects, suggesting that enlargement of adipose tissue mass is the principal driver of abnormal FFA homeostasis [129].
Adipose tissue can grow in size by either hypertrophy, which involves the enlargement of existing adipocytes, or hyperplasia, which involves the generation of new fat cells from preadipocytes via adipogenesis, resulting in an increase in the number of tiny adipocytes [130]. Subcutaneous adipose tissue is more expandable than visceral adipose tissue in humans, whereas the opposite is true in C57BL/6J male mice [131]. Female mice, interestingly, show expandability of both adipose tissue depots in response to Western diet feeding, suggesting that sex hormones and other sex-dependent elements play a role in this process [131, 132]. Pathological adipose tissue expandability under situations of overnutrition, particularly adipose tissue hypertrophy, has got a lot of attention as a likely cause of IR. Indeed, first-degree relatives of patients with T2D have greater amounts of hypertrophic adipose tissue, implying that changes in cell size—presumably due to defective adipogenesis—represent an early event in the pathophysiology of T2D. Hypertrophic large adipocytes are linked to poor metabolic outcomes when compared to hyperplastic adipocytes [39, 133], which have been shown to confer metabolic health in obesity [134, 135, 136]. More importantly, hypertrophic adipocytes may contribute to an increase in circulating FFA levels due to their reduced FFA storage capacity. Reduced preadipocyte differentiation, diminished de novo lipogenesis or FFA uptake in hypertrophic adipocytes, and/or reduced adipose tissue expandability due to physical limits on expanding cell size may all contribute to decreased lipid storage capacity by the hypertrophic adipose tissue. Furthermore, adipogenesis abnormalities may result in decreased generation of beige adipocytes, thereby contributing to higher circulating FFA levels; indeed, beige adipocytes differentiate from a subpopulation of progenitors resident in white adipose tissue and have the ability to promote FFA oxidation through thermogenesis [137, 138].
10.2 Circulatory factors released from adipocytes
Adipose tissue secretes a number of factors (termed “adipokines”) into the bloodstream that regulate energy metabolism. These factors include cytokines, hormones, extracellular matrix proteins, as well as growth and vasoactive factors. The type of adipose tissue expansion has been demonstrated to impact the secretion of certain of these factors under IR conditions. Since the discovery of leptin as the first adipokine [139], a growing list of adipose tissue-secreted factors implicated in IR has been discovered, with roles in IR that are either protective or causative [20, 140].
Leptin, for example, regulates whole-body energy metabolism by acting on feeding centers in the brain to suppress food intake and increase energy expenditure; leptin deficiency causes obesity, hyperinsulinemia, IR and impaired glucose homeostasis [141]. Adiponectin, another well-known adipokine secreted from adipocytes, has been linked to regulation of cell insulin sensitivity. In humans, circulating adiponectin levels are favorably linked with whole-body insulin sensitivity; additionally, physical training increases circulating adiponectin levels and the expression of its receptors in muscle, which may mediate the improvement of IR in response to exercise [142]. Surprisingly, small and subcutaneous adipocytes release more adiponectin than visceral or large adipocytes [143]. Anti-atherogenic, anti-inflammatory, and insulin-sensitizing effects of adiponectin have also been discovered [144]. It is worth mentioning, however, that while adiponectin’s positive benefits in rats are outstanding, the role of this adipokine in humans is less obvious, and Mendelian randomization studies on adiponectin’s relationship with metabolic disease in humans have generated inconsistent results [145, 146].
Adipocytes release a variety of substances, including metabolites like lipids and extracellular vesicles that contain proteins and microRNAs. Branched fatty acid esters of hydroxy fatty acids (FAHFAs) are a unique class of lipids synthesized in adipocytes that have been shown to increase insulin sensitivity and reduce inflammation; accordingly, individuals with IR have lower circulating FAHFA levels [147]. As a result, further research into this metabolite class is necessary. Adipocytes, for example, release tiny lipid-encapsulated extracellular vesicles into the bloodstream. These vesicles may alter metabolic processes in other target tissues, such as the liver, according to increasing evidence based on mouse studies. MicroRNAs represent one of the components found in extracellular vesicles that have been linked to this mechanism. While investigations on microRNAs are intriguing, many fundamental aspects about the mechanism of their controlled secretion and their tissue targeting and entry into target cells remain unknown [148, 149].
Many circulating factors are also produced by other adipose tissue-resident cells, such as immune or vascular cells, rather than by adipocytes themselves (the so-called “stromal vascular fraction” of adipose tissue). Some of these adipokines, such as tumor necrosis factor (TNF), resistin or vascular endothelial growth factor (VEGF), are important regulators of tissue homeostasis and may be secreted as a result of adipose tissue enlargement during the development of obesity [150]. Nonetheless, inflammatory cytokines have been widely suggested as possible IR-inducing adipokines, and several of these factors have significant proinflammatory activities [151, 152, 153].
11. Inflammation and insulin resistance
It is now well recognized that cells of both innate and adaptive immunity, notably macrophages, infiltrate hypertrophic adipose tissue in most obesity models, and that this is accompanied by a loss of immunosuppressive regulatory T cells in visceral fat depots [154]. When macrophages in adipose tissue are activated in response to overnutrition, they polarize towards a proinflammatory phenotype and release cytokines that may trigger IR in all metabolic tissues [155]. Diet-induced obesity in mice and humans is unmistakably linked to elevated levels of systemic inflammatory markers, including C-reactive protein (CRP) and enhanced immune cell infiltration of adipose tissue and other organs [156]. In addition, inflammatory cytokines, such as TNF, can elicit IR in metabolic tissues when infused in humans [157]. Although macrophage infiltration into hypertrophic adipose tissue is well documented, the role of inflammation in IR is convoluted and controversial; for example, inflammatory markers are not elevated in first-degree relatives of T2D patients [158]. Furthermore, in Western diet-fed mice, tissue IR occurs before the adipose tissue infiltration by a considerable number of immune cells, and genetic or pharmacological anti-inflammatory methods do not prevent the development of Western diet-induced IR [159, 160]. The administration of a neutralizing antibody against interleukin-1 (IL-1), a proinflammatory cytokine implicated in IR, to approximately 4000 patients with T2D and almost 5000 subjects with prediabetes resulted in a significant decrease in CRP levels, as well as in a modest positive effect on cardiovascular outcomes, but without reducing the frequency of new-onset T2D or increasing fasting glucose levels [161, 162, 163].
Overall, evidence suggests that adipose tissue infiltration by macrophages is unlikely to be the major cause of IR. Macrophage infiltration into the growing adipose tissue may affect its function in addition to systemic inflammation, but the exact impact of this infiltration is unknown [164]. Anti-inflammatory macrophages (M2), on the other hand, have been shown to promote angiogenesis and preadipocyte differentiation, which aids adipose tissue expansion [165, 166]. The diversity of cytokines, their concentrations, and the timing of their release into the tissue are likely to have a considerable impact on the final biological response, contributing to the observed inconsistent results. The ability of genetically induced adipocyte IR to elicit adipose tissue inflammation adds to the growing body of evidence that inflammation may be a consequence rather than a cause of IR. Hyperinsulinemia has been shown to induce adipose tissue inflammation, implying that the latter is a late event in the IR pathophysiology [30].
12. Intracellular mediators and insulin resistance
Many extrinsic stimuli and genetic alterations can antagonize insulin action in vitro and in vivo, and their investigation has led to the identification of a series of molecules as putative intracellular mediators of IR. In the sections that follow, we will look at the role of a few intracellular components that have got a lot of attention as drivers of IR. It is worth noting that mechanisms of action of these components are not well-established yet, and further research is needed to better understand their role in IR development.
12.1 Accumulation of ceramides
Ceramides have been implicated as IR mediators by a large body of research. Ceramides are essential precursors of most of the complex sphingolipids localized in lipid bilayers, including sphingosine, sphingomyelins, and glucosylceramides. Ceramides accumulate in muscle, liver and adipose tissue of subjects with IR, according to human and animal studies [167, 168, 169, 170]. In insulin-resistant tissues, the levels of 16- or 18-carbon chain-length ceramides are raised, whereas the levels of other chain-length ceramides are not consistently changed [171, 172]. Indeed, in adipose tissue from obese subjects, the level of ceramide synthase isoform 6 (CERS6), which synthesizes C16 ceramide, is raised [171]. Surprisingly, the presence of a double bond in the ceramide backbone promotes IR, as ablation of the enzyme responsible for its formation (dihydroceramide desaturase 1) abrogates IR [173]. While it is unclear how specific extrinsic mediators of IR cause increased intracellular ceramide levels, it is possible that excess FFAs serve as a crucial substrates for ceramide biosynthesis [174, 175, 176].
Another theory connects intracellular ceramide to levels of circulating adiponectin. Ceramidase activity is found on adiponectin receptors, and lower adiponectin levels in IR may lead to decreased ceramidase activity and, consequently, to higher ceramide levels [177, 178]. AMP-activated protein kinase (AMPK), a major metabolic sensor that regulates mitochondrial biogenesis and metabolism, is activated by adiponectin, potentially regulating ceramide via increased mitochondrial lipid oxidation [179]. By using small-molecule inhibitors or genetic deletion of ceramide-producing enzymes to neutralize ceramide accumulation in metabolic organs, researchers were able to reverse or prevent IR induced by the Western diet in C57BL/6 mice with diet-induced obesity [122]. The relationship between ceramide and decreased insulin action is not univocal, as it is for many possible intracellular mediators of IR. In fact, ceramide suppresses AKT activity, although IR is unlikely to be caused by defects in AKT, which is a proximal arm of insulin signaling (as it has previously been mentioned). Ceramide could be part of a wider, IR-related stress mechanism that leads to mitochondrial dysfunction and to the production of reactive oxygen species (ROS). Ceramide has also been connected to the release of pro-inflammatory cytokines, which have been involved in IR, as it has previously been described [180, 181].
12.2 Accumulation of diacylglycerol (DAG)
Another popular theory for the cause of IR is the accumulation of diacylglycerols (DAGs) in muscle, adipocytes and liver, as a result of elevated serum FFA levels [182, 183]. Protein kinase C (PKC) is recruited to the plasma membrane by DAGs, where it phosphorylates and inhibits insulin receptor kinase activity. While it is quite plausible that DAG levels are elevated in insulin-resistant tissues, a scenario in which DAG-dependent phosphorylation of the insulin receptor is the major cause of IR raises a number of questions. Given the “spareness” of the insulin receptor and proximal signaling intermediates, it is doubtful that IR is caused solely by abnormalities in these components, at least in muscle. In contrast to other insulin-responsive proteins, the stoichiometry of insulin receptor phosphorylation at the region implicated in DAG-mediated IR is low and not detectable by conventional phosphopeptide analysis [79, 104, 184]. PKC deletion in the liver had little effect on whole-body insulin sensitivity in mice, indicating against PKC being a key target of DAG-induced IR in that tissue [79, 104], although this has since been challenged by studies in rats showing that acute knockdown of PKC in the liver protected animals from IR. However, antisense oligonucleotides were delivered systemically, which could target PKC expression in other organs. While technical differences between these studies and others have been suggested as a reason for the discrepancies observed [183], there appears to be enough disagreement about the role of the DAG-PKC-insulin receptor pathway in IR to warrant further investigation and, in particular, validation by multiple independent laboratories [185].
12.3 Mitochondrial dysfunction and reactive oxygen species (ROS)
IR has been linked to a decrease in mitochondrial function. Mitochondrial dysfunction is a term that has been used to describe a variety of mitochondrial phenotypes, including decreased respiratory capacity and ATP production, decreased number of mitochondria, accumulated mitochondrial damage due to defects in mitophagy, and altered mitochondrial morphology caused by changes in mitochondrial fission-fusion dynamics. Many of these alterations are also linked to an increase in mitochondrial ROS generation, which has long been linked to IR [186, 187, 188].
It is not unexpected that IR is linked to higher levels of reactive oxygen species (ROS). This is due to the fact that IR is frequently accompanied by a positive energy balance, which leads to an excess of reducing equivalents (NADH and FADH2). This determines a reductive stress on the mitochondrial respiratory electron transport chain, which invariably results in the formation of free electrons and, as a result, in an increased production of various forms of ROS [189]. Furthermore, enhanced ROS production has been found in response to a variety of extracellular stressors linked to IR, including inflammation [190]. Superoxide, H2O2, reactive nitrogen andoxidized lipids accumulate in insulin-resistant cells or tissues, and a mitochondria-targeted small molecule transiently produced mitochondrial ROS in muscle and adipocytes, causing IR. As a result, attempts to reduce ROS levels have been proven to reverse or prevent IR in mice [191, 192, 193, 194].
Reduced levels of coenzyme Q (CoQ) have recently been linked to IR in humans [44]. In mitochondria, CoQ is a key component of the electron transport chain, transferring electrons from complex I or II to complex III. Furthermore, unlike complex I, CoQ receives electrons directly from the electron-transferring flavoprotein, and this is unrelated to proton pumping or mitochondrial membrane potential, relying only on the availability of oxidized CoQ. Reduced CoQ accumulates, causing reductive stress in complex I, complex II and other dehydrogenases that feed electrons into the CoQ pool, resulting in increased ROS production [195]. As a result, lowering the total CoQ pool [44] will most likely lower the ROS production threshold at a given energy demand-supply ratio. It is also worth noting that FFA oxidation produces far more ROS than carbohydrate oxidation [195]. This is because the electron-transferring flavoprotein feeds a higher proportion of reducing equivalents straight into the CoQ pool during FFA oxidation. Therefore, as lipid metabolism increases, the supply of reducing equivalents outnumbers the demand, lowering the ratio of oxidized to reduced CoQ. This is likely worsened when total CoQ levels are low, as seen in IR [44], resulting in reductive stress and increased ROS production. The mechanism that regulates CoQ levels in IR is unknown. Intriguingly, statins, which are commonly used as cholesterol-lowering drugs, have been linked to IR in humans [196], with the possibility that this relationship is related to the statin-induced reductions in CoQ biosynthesis [44]. Unfortunately, given the low bioavailability of CoQ , oral supplements, which are frequently recommended as an antioxidant strategy, are unlikely to be successful in replenishing the mitochondrial CoQ pool in patients with IR or even in individuals who take statins. Other hazardous intermediates can be generated, in addition to ROS, as a result of mitochondrial respiration abnormalities. Acylcarnitine is an example of incompletely oxidized lipids produced by lipid overload. Acylcarnitine has been reported to accumulate in IR, indicating a deficiency in or an overabundance of the mitochondrial oxidative ability. In this regard, it has been postulated that lipid-induced mitochondrial stress mediates IR, although the exact mechanisms remain elusive [197].
12.4 Insulin resistance associated with stress pathway
Many of the pathways involved in IR pathophysiology, such as those involving ceramides, DAGs or ROS, are now being linked as part of what we call an “intracellular IR stress pathway”, according to new evidence. Ceramide, for example, promotes mitochondrial fission and ROS production [198, 199]. In subjects with IR, the quantity of mitochondrial ceramide is higher, and enzymes involved in ceramide biosynthesis have been found in mitochondria [185, 200, 201, 202, 203]. Ceramide is involved in apoptosis triggered by mitochondria in some cells, including insulin-producing pancreatic beta cells, but not in other metabolic tissues [204, 205, 206]. Ceramide also contributes to endoplasmic reticulum stress, which frequently co-occurs with mitochondrial stress and has been proposed as a driver of IR, where endoplasmic reticulum stress causes JNK activation, which, as previously described, affects the insulin signaling pathway via inhibitory IRS1 Ser/Thr phosphorylation [204, 205, 206]. Ceramide also induces PKC, a DAG-regulated kinase, to translocate to mitochondria, activating it and causing mitochondrial damage through an unknown mechanism [207]. Ceramides and DAGs are also biochemically connected; sphingomyelin synthase, for example, converts ceramide to DAG. Finally, in rats, reducing mitochondrial ROS levels with mitochondria-targeted catalase improved insulin sensitivity while lowering muscle DAG levels [208]. The potential connection of many of these suspected IR-causing elements into a dynamic network should help to resolve some of the current debates on this topic.
12.5 Signals from the mitochondria
Despite the interest in mitochondrial dysfunction in IR, it is unclear how intramitochondrial signals, like ceramide or ROS, may cause changes in insulin action, such as impaired GLUT4 translocation, which occurs mostly in the cytosol. The mitochondrial permeability transition pore (mPTP), a multiprotein complex located in the inner mitochondrial membrane, is a promising candidate for “inside-out” mitochondrial signaling because it opens under conditions of mitochondrial stress—most notably involving mitochondrial ROS—to allow molecules to be transported from mitochondria to the cytoplasm [209]. In L6 myotubes, inhibiting mPTP prevented ceramide- or palmitate-induced IR, and mice with defective mPTP opening were protected from diet-induced IR in skeletal muscle [210]. Although at least a part of the impact is attributable to its anti-obesogenic effect, deletion of mPTP in the liver has been shown to protect mice from liver steatosis and IR [211].
13. Conclusions and perspectives
The rising frequency of IR, as well as its crucial involvement in a variety of diseases, demands a greater understanding of the processes behind IR pathogenesis and how they interact with genetics and various surroundings, notably dietary factors. We have attempted to offer an overview of the main mechanisms hypothesized to contribute to IR in this chapter, highlighting both supportive and non-confirmatory evidence when appropriate. Many of the molecules and processes studied as causative in IR, in our opinion, function in series as a connected pathway or a loop rather than acting independently. Unfortunately, there has been a recent trend to describe IR as a dysfunction of insulin signaling, regardless of whether a simultaneous examination of insulin action on glucose metabolism has identified a defect in the latter process. We feel that this method has produced significant problems in the field, and we wish to send a message that simple, unitary errors in proximal insulin signaling are unlikely to be a major cause of IR. Rather, IR develops as a result of a variety of challenges that disrupt cellular homeostasis, resulting in cellular stress that can have a variety of deleterious consequences on insulin signal sensing and transmission.
The difficulty in translating findings from model organisms to humans, particularly in terms of differentiating IR causation from the multiplicity of effects, is a key roadblock in investigating the underpinnings of IR. By discovering causal genetic variants, human genetics holds a lot of promise for tackling this problem. However, genetics can only explain a portion of the pathophysiology of IR. Environmental variables play a crucial role in determining susceptibility to IR development and interact with genetics. Furthermore, the heterogeneity of metabolic diseases like T2D demands detailed phenotyping. Focusing on phenotypes that has better track with IR has proven difficult to achieve in the large cohorts. It is required to identify genetic polymorphisms that only explain a small proportion of disease in the human population. Despite these limitations, a number of genetic loci linked to human IR have been discovered, leading to a renewed focus on adipose tissue enlargement as a critical aspect of IR. However, since IR is a systemic condition, we expect future investigations to discover variations in genes governing multiple cellular processes throughout organs as linked to IR pathophysiology.
A more systematic approach involving large-scale omics to analyze the molecular landscape rather than relying on individual components as causal would be required to gain a better understanding of IR. Moreover, while knockout mice have been critical in characterizing the biochemistry of insulin action, they have also sparked numerous debates. One reason for this is that gene deletions typically result in adaptive processes that are difficult to define and may have limited physiological value, as indicated in a recent study with muscle-specific Akt gene-knockout mice [58]. In animals with both insulin and insulin-like growth factor 1 (IGF-1) receptors removed in muscle, similar adaptation mechanisms have been reported [212].
The ultimate goal of understanding mechanisms behind IR is to develop new, effective anti-IR therapeutic strategies. One key point to consider in this endeavor is whether such therapies would be beneficial if the initial insult—nutritional overload—persists. While IR is typically considered abnormal, as it is linked to a variety of disease outcomes, it is also a prevalent component of many normal physiological states, such as starvation, pregnancy, and hibernation. IR is believed to play a protective or adaptive role in such conditions, supporting survival by saving glucose for the brain and other vital tissues and organs or for the fetus during pregnancy. It is possible that IR has a similar function in metabolic disease. Since the primary metabolic tissues are frequently exposed to potentially harmful quantities of nutrients, IR could be a protective mechanism that helps to prevent tissue nutrition overload [190]. However, this comes at a price, namely concomitant hyperinsulinemia, which is the most serious pathophysiological consequence of IR. Insulin-sensitizing drugs may thus act as a “circuit breaker”, reducing hunger, inflammation and IR by suppressing hyperinsulinemia. As a result, we believe there is still a strong need to describe the molecular characteristics that drive IR in order to identify appropriate targets that can break the IR vicious cycle.
Acknowledgments
The authors are also thankful to Guru Nanak Dev University (Amritsar, Punjab, India) for providing various facilities to carry out the present work.
Conflict of interest
The authors declare no conflict of interest.
\n',keywords:"insulin, insulin receptor, insulin resistance, glucose uptake, glucose metabolism",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/82197.pdf",chapterXML:"https://mts.intechopen.com/source/xml/82197.xml",downloadPdfUrl:"/chapter/pdf-download/82197",previewPdfUrl:"/chapter/pdf-preview/82197",totalDownloads:7,totalViews:0,totalCrossrefCites:0,dateSubmitted:"December 13th 2021",dateReviewed:"April 4th 2022",datePrePublished:"June 11th 2022",datePublished:null,dateFinished:"June 11th 2022",readingETA:"0",abstract:"Insulin resistance (IR) is a condition in which insulin-mediated regulation of glucose metabolism in body tissues (primarily liver, adipose tissue and skeletal muscle) becomes disrupted. IR is a characteristic marker of type 2 diabetes and cardiovascular diseases. IR is generally associated with metabolic abnormalities, including hyperinsulinemia, impaired glucose homeostasis, hyperlipidemia and obesity. IR can arise from pathological, genetic and environmental factors or from a combination of these factors. Studies conducted in recent decades showcase the important role of adipose tissue in the development of IR via release of lipids and different circulating factors. These extracellular factors influence the intracellular levels of intermediates including ceramide and various lipids that influence the cell responsiveness to insulin. These intermediates are suggested to promote IR via inhibition of one or more components of insulin signaling pathway (e.g., insulin receptor, insulin receptor substrate proteins). This chapter will shed light on various molecular mechanisms and factors contributing to IR, which will help the researchers to design potential therapeutic strategies and interventions for efficiently managing IR and its related disorders.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/82197",risUrl:"/chapter/ris/82197",signatures:"Atamjit Singh, Nikhita Ghai and PreetMohinder Singh Bedi",book:{id:"11261",type:"book",title:"Insulin Resistance - Evolving Concepts and Treatment Strategies",subtitle:null,fullTitle:"Insulin Resistance - Evolving Concepts and Treatment Strategies",slug:null,publishedDate:null,bookSignature:"Dr. Marco Infante",coverURL:"https://cdn.intechopen.com/books/images_new/11261.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-502-7",printIsbn:"978-1-80355-501-0",pdfIsbn:"978-1-80355-503-4",isAvailableForWebshopOrdering:!0,editors:[{id:"409412",title:"Dr.",name:"Marco",middleName:null,surname:"Infante",slug:"marco-infante",fullName:"Marco Infante"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Pathway to insulin resistance",level:"1"},{id:"sec_3",title:"3. The trio-axis of obesity-hyperinsulinemia-insulin resistance",level:"1"},{id:"sec_4",title:"4. Insulin resistance and hyperinsulinemia",level:"1"},{id:"sec_5",title:"5. Heterogeneity in the development of insulin resistance and progression of metabolic disease and T2D",level:"1"},{id:"sec_6",title:"6. Tissue-specific progression to insulin resistance",level:"1"},{id:"sec_7",title:"7. Impaired insulin signaling in insulin resistance",level:"1"},{id:"sec_8",title:"8. Insulin resistance and insulin signaling at the proximal level",level:"1"},{id:"sec_9",title:"9. GLUT4 and insulin resistance",level:"1"},{id:"sec_10",title:"10. Adipose tissue and insulin resistance",level:"1"},{id:"sec_10_2",title:"10.1 Adipose tissue dysfunction",level:"2"},{id:"sec_11_2",title:"10.2 Circulatory factors released from adipocytes",level:"2"},{id:"sec_13",title:"11. Inflammation and insulin resistance",level:"1"},{id:"sec_14",title:"12. Intracellular mediators and insulin resistance",level:"1"},{id:"sec_14_2",title:"12.1 Accumulation of ceramides",level:"2"},{id:"sec_15_2",title:"12.2 Accumulation of diacylglycerol (DAG)",level:"2"},{id:"sec_16_2",title:"12.3 Mitochondrial dysfunction and reactive oxygen species (ROS)",level:"2"},{id:"sec_17_2",title:"12.4 Insulin resistance associated with stress pathway",level:"2"},{id:"sec_18_2",title:"12.5 Signals from the mitochondria",level:"2"},{id:"sec_20",title:"13. Conclusions and perspectives",level:"1"},{id:"sec_21",title:"Acknowledgments",level:"1"},{id:"sec_24",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Himsworth HP. Diabetes mellitus: Its differentiation into insulin-sensitive and insulin-insensitive types. 1936. International Journal of Epidemiology. 2013;42:1594-1598'},{id:"B2",body:'Jee SH, Kim HJ, Lee J. Obesity, insulin resistance and cancer risk. Yonsei Medical Journal. 2005;46(4):449-455'},{id:"B3",body:'Suzanne M. Insulin resistance and neurodegeneration: Progress towards the development of new therapeutics for Alzheimer’s disease. Drugs. 2017;77(1):47-65'},{id:"B4",body:'Pérez-Tasigchana RF, León-Muñoz LM, Lopez-Garcia E, Gutierrez-Fisac JL, Laclaustra M, Rodríguez-Artalejo F, et al. Metabolic syndrome and insulin resistance are associated with frailty in older adults: A prospective cohort study. Age and Ageing. 2017;46(5):807-812'},{id:"B5",body:'Chawla A, Chawla R, Jaggi S. Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian Journal of Endocrinology and Metabolism. 2016;20(4):546'},{id:"B6",body:'Singh B, Saxena A. Surrogate markers of insulin resistance: A review. World Journal of Diabetes. 2010;1(2):36'},{id:"B7",body:'Philipson LH. Harnessing heterogeneity in type 2 diabetes mellitus. Nature Reviews. Endocrinology. 2020;16:79-80'},{id:"B8",body:'Ahlqvist E et al. Novel subgroups of adult-onset diabetes and their association with outcomes: A data-driven cluster analysis of six variables. The Lancet Diabetes and Endocrinology. 2018;6:361-369'},{id:"B9",body:'James DE, Strube M, Mueckler M. Molecular cloning and characterization of an insulin-regulatable glucose transporter. Nature. 1989;338:83-87'},{id:"B10",body:'Birnbaum MJ. Identification of a novel gene encoding an insulin-responsive glucose transporter protein. Cell. 1989;57:305-315'},{id:"B11",body:'Bryant NJ, Govers R, James DE. Regulated transport of the glucose transporter GLUT4. Nature Reviews. Molecular Cell Biology. 2002;3:267-277'},{id:"B12",body:'Tunduguru R, Thurmond DC. Promoting glucose transporter-4 vesicle trafficking along cytoskeletal tracks: PAK-Ing them out. Frontiers in Endocrinology. 2017;20:329'},{id:"B13",body:'Yeh JI, Gulve EA, Rameh L, Birnbaum MJ. The effects of wortmannin on rat skeletal muscle. Dissociation of signaling pathways for insulin- and contraction-activated hexose transport. The Journal of Biological Chemistry. 1995;270:2107-2111'},{id:"B14",body:'Clemmensen C et al. Gut-brain cross-talk in metabolic control. Cell. 2017;168:758-774'},{id:"B15",body:'Rizza RA, Mandarino LJ, Genest J, Baker BA, Gerich JE. Production of insulin resistance by hyperinsulinaemia in man. Diabetologia. 1985;28:70-75'},{id:"B16",body:'Erion KA, Corkey BE. Hyperinsulinemia: A cause of obesity? Current Obesity Reports. 2017;6:178-186'},{id:"B17",body:'Lillioja S et al. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. The New England Journal of Medicine. 1993;329:1988-1992'},{id:"B18",body:'Vaag A, Henriksen JE, Beck-Nielsen H. Decreased insulin activation of glycogen synthase in skeletal muscles in young nonobese Caucasian first-degree relatives of patients with non-insulindependent diabetes mellitus. The Journal of Clinical Investigation. 1992;89:782-788'},{id:"B19",body:'Hollenbeck C, Reaven GM. Variations in insulin-stimulated glucose uptake in healthy individuals with normal glucose tolerance. The Journal of Clinical Endocrinology and Metabolism. 1987;64:1169-1173'},{id:"B20",body:'Ghaben AL, Scherer PE. Adipogenesis and metabolic health. Nature Reviews. Molecular Cell Biology. 2019;20:242-258'},{id:"B21",body:'Jacob S et al. Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. Diabetes. 1999;48:1113-1119'},{id:"B22",body:'Lim K, Haider A, Adams C, Sleigh A, Savage D. Lipodystrophy: A paradigm for understanding the consequences of ‘overloading’ adipose tissue. Physiological Reviews. 2020;101:907-993'},{id:"B23",body:'Akinci B, Sahinoz M, Oral E. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Lipodystrophy Syndromes: Presentation and Treatment. South Dartmouth (MA): MDText.com, Inc.; 2000'},{id:"B24",body:'Blüher M. Metabolically healthy obesity. Endocrine Reviews. 2020;41:405-420'},{id:"B25",body:'Thomas DD, Corkey BE, Istfan NW, Apovian CM. Hyperinsulinemia: An early indicator of metabolic dysfunction. Journal of the Endocrine Society. 2019;3(9):1727-1747'},{id:"B26",body:'Pontiroli AE, Alberetto M, Capra F, Pozza G. The glucose clamp technique for the study of patients with hypoglycemia: Insulin resistance as a feature of insulinoma. Journal of Endocrinological Investigation. 1990;13:241-245'},{id:"B27",body:'Marbán SL, Roth J. Transgenic hyperinsulinemia: A mouse model of insulin resistance and glucose intolerance without obesity. In: Shafrir E, editor. Lessons from Animal Diabetes VI: 75th Anniversary of the Insulin Discovery. Boston, MA: Birkhäuser; 1996. pp. 201-224'},{id:"B28",body:'Gray SL, Donald C, Jetha A, Covey SD, Kieffer TJ. Hyperinsulinemia precedes insulin resistance in mice lacking pancreatic beta-cell leptinsignaling. Endocrinology. 2010;151:4178-4186'},{id:"B29",body:'Alemzadeh R, Slonim AE, Zdanowicz MM, Maturo J. Modification of insulin resistance by diazoxide in obese Zucker rats. Endocrinology. 1993;133:705-712'},{id:"B30",body:'Pedersen DJ et al. A major role of insulin in promoting obesity-associated adipose tissue inflammation. Molecular Metabolism. 2015;4:507-518'},{id:"B31",body:'Templeman NM et al. Reduced circulating insulin enhances insulin sensitivity in old mice and extends lifespan. Cell Reports. 2017;20:451-463'},{id:"B32",body:'Czech MP. Insulin action and resistance in obesity and type 2 diabetes. Nature Medicine. 2017;23:804-814'},{id:"B33",body:'Tan S-X et al. Selective insulin resistance in adipocytes. The Journal of Biological Chemistry. 2015;290:11337-11348'},{id:"B34",body:'Tonks KT et al. Impaired Akt phosphorylation in insulin-resistant human muscle is accompanied by selective and heterogeneous downstream defects. Diabetologia. 2013;56:875-885'},{id:"B35",body:'Brown MS, Goldstein JL. Selective versus total insulin resistance: A pathogenic paradox. Cell Metabolism. 2008;7:95-96'},{id:"B36",body:'Hillgartner FB, Salati LM, Goodridge AG. Physiological and molecular mechanisms involved in nutritional regulation of fatty acid synthesis. Physiological Reviews. 1995;75:47-76'},{id:"B37",body:'Hellerstein MK, Schwarz JM, Neese RA. Regulation of hepatic de novo lipogenesis in humans. Annual Review of Nutrition. 1996;16:523-557'},{id:"B38",body:'Titchenell PM et al. Direct hepatocyte insulin signaling is required for lipogenesis but is dispensable for the suppression of glucose production. Cell Metabolism. 2016;23:1154-1166'},{id:"B39",body:'Hammarstedt A, Gogg S, Hedjazifar S, Nerstedt A, Smith U. Impaired adipogenesis and dysfunctional adipose tissue in human hypertrophic obesity. Physiological Reviews. 2018;98:1911-1941'},{id:"B40",body:'Kolterman OG, Insel J, Saekow M, Olefsky JM. Mechanisms of insulin resistance in human obesity: Evidence for receptor and postreceptor defects. The Journal of Clinical Investigation. 1980;65:1272-1284'},{id:"B41",body:'Anjana RM, Pradeepa R, Unnikrishnan R, Tiwaskar M, Aravind SR, Saboo B, et al. New and unique clusters of type 2 diabetes identified in Indians. The Journal of the Association of Physicians of India. 2021;69(2):58-61'},{id:"B42",body:'Jia Q , Morgan-Bathke ME, Jensen MD. Adipose tissue macrophage burden, systemic inflammation, and insulin resistance. American Journal of Physiology. Endocrinology and Metabolism. 2020;319:E254-E264'},{id:"B43",body:'Turner N et al. Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding. Diabetologia. 2013;56:1638-1648'},{id:"B44",body:'Fazakerley DJ et al. Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance. eLife. 2018;7:e32111'},{id:"B45",body:'Perry RJ et al. Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes. Cell. 2015;160:745-758'},{id:"B46",body:'Van der Heijden RA, Sheedfar F, Morrison MC, Hommelberg PP, Kor D, Kloosterhuis NJ, et al. High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL/6j mice. Aging (Albany NY). 2015;7(4):256'},{id:"B47",body:'Ali O. Genetics of type 2 diabetes. World Journal of Diabetes. 2013;4(4):114'},{id:"B48",body:'Minokoshi Y, Kahn CR, Kahn BB. Tissue-specific ablation of the GLUT4 glucose transporter or the insulin receptor challenges assumptions about insulin action and glucose homeostasis. The Journal of Biological Chemistry. 2003;278:33609-33612'},{id:"B49",body:'Kim JK et al. Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4. The Journal of Clinical Investigation. 2001;108:153-160'},{id:"B50",body:'Gancheva S, Jelenik T, Álvarez-Hernández E, Roden M. Interorgan metabolic crosstalk in human insulin resistance. Physiological Reviews. 2018;98:1371-1415'},{id:"B51",body:'Severinsen MCK, Pedersen BK. Muscle-organ crosstalk: The emerging roles of myokines. Endocrine Reviews. 2020;41:594-609'},{id:"B52",body:'Burchfield JG et al. High dietary fat and sucrose results in an extensive and time-dependent deterioration in health of multiple physiological systems in mice. The Journal of Biological Chemistry. 2018;293:5731-5745'},{id:"B53",body:'Hoehn KL et al. IRS1-independent defects define major nodes of insulin resistance. Cell Metabolism. 2008;7:421-433'},{id:"B54",body:'Copps KD, White MF. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia. 2012;55:2565-2582'},{id:"B55",body:'Kahn CR et al. The syndromes of insulin resistance and acanthosisnigricans. Insulin-receptor disorders in man. The New England Journal of Medicine. 1976;294:739-745'},{id:"B56",body:'Kono T, Barham FW. The relationship between the insulin-binding capacity of fat cells and the cellular response to insulin. Studies with intact and trypsin-treated fat cells. The Journal of Biological Chemistry. 1971;246:6210-6216'},{id:"B57",body:'Kahn CR. Insulin resistance, insulin insensitivity, and insulin unresponsiveness: A necessary distinction. Metabolism. 1978;27:1893-1902'},{id:"B58",body:'Olefsky JM, Kolterman OG, Scarlett JA. Insulin action and resistance in obesity and noninsulindependent type II diabetes mellitus. The American Journal of Physiology. 1982;243:E15-E30'},{id:"B59",body:'Camps M et al. Evidence for the lack of spare high-affinity insulin receptors in skeletal muscle. The Biochemical Journal. 1992;285:993-999'},{id:"B60",body:'Gumà A et al. Effect of benzyl succinate on insulin receptor function and insulin action in skeletal muscle: Further evidence for a lack of spare high-affinity insulin receptors. Molecular and Cellular Endocrinology. 1993;91:29-33'},{id:"B61",body:'Fehlmann M, Morin O, Kitabgi P, Freychet P. Insulin and glucagon receptors of isolated rat hepatocytes: Comparison between hormone binding and amino acid transport stimulation. Endocrinology. 1981;109:253-261'},{id:"B62",body:'Merry TL et al. Impairment of insulin signalling in peripheral tissue fails to extend murine lifespan. Aging Cell. 2017;16:761-772'},{id:"B63",body:'Czech MP. Cellular basis of insulin insensitivity in large rat adipocytes. The Journal of Clinical Investigation. 1976;57:1523-1532'},{id:"B64",body:'Melvin A, O’Rahilly S, Savage DB. Genetic syndromes of severe insulin resistance. Current Opinion in Genetics & Development. 2018;50:60-67'},{id:"B65",body:'Crouthamel M-C et al. Mechanism and management of AKT inhibitor-induced hyperglycemia. Clinical Cancer Research. 2009;15:217-225'},{id:"B66",body:'Nandi A, Kitamura Y, Kahn CR, Accili D. Mouse models of insulin resistance. Physiological Reviews. 2004;84:623-647'},{id:"B67",body:'Jaiswal N et al. The role of skeletal muscle Akt in the regulation of muscle mass and glucose homeostasis. Molecular Metabolism. 2019;28:1-13'},{id:"B68",body:'Lu M et al. Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. Nature Medicine. 2012;18:388-395'},{id:"B69",body:'Tan S-X et al. Amplification and demultiplexing in insulin-regulated Akt protein kinase pathway in adipocytes. The Journal of Biological Chemistry. 2012;287:6128-6138'},{id:"B70",body:'Ng Y et al. Cluster analysis of insulin action in adipocytes reveals a key role for Akt at the plasma membrane. The Journal of Biological Chemistry. 2010;285:2245-2257'},{id:"B71",body:'Larance M et al. Global phosphoproteomics identifies a major role for AKT and 14-3-3 in regulating EDC3. Molecular & Cellular Proteomics. 2010;9:682-694'},{id:"B72",body:'Trefely S et al. Kinome screen identifies PFKFB3 and glucose metabolism as important regulators of the insulin/insulin-like growth factor (IGF)-1 signaling pathway. The Journal of Biological Chemistry. 2015;290:25834-25846'},{id:"B73",body:'Ricort JM, Tanti JF, Van Obberghen E, Le Marchand-Brustel Y. Alterations in insulin signalling pathway induced by prolonged insulin treatment of 3T3-L1 adipocytes. Diabetologia. 1995;38:1148-1156'},{id:"B74",body:'Kurowski TG et al. Hyperglycemia inhibits insulin activation of Akt/protein kinase B but not phosphatidylinositol 3-kinase in rat skeletal muscle. Diabetes. 1999;48:658-663'},{id:"B75",body:'Oku A et al. Inhibitory effect of hyperglycemia on insulin-induced Akt/protein kinase B activation in skeletal muscle. American Journal of Physiology. Endocrinology and Metabolism. 2001;280:E816-E824'},{id:"B76",body:'Yuasa T et al. Platelet-derived growth factor stimulates glucose transport in skeletal muscles of transgenic mice specifically expressing platelet-derived growth factor receptor in the muscle, but it does not affect blood glucose levels. Diabetes. 2004;53:2776-2786'},{id:"B77",body:'Draznin B. Molecular mechanisms of insulin resistance: Serine phosphorylation of insulin receptor substrate-1 and increased expression of p85alpha: The two sides of a coin. Diabetes. 2006;55:2392-2397'},{id:"B78",body:'Copps KD et al. Irs1 serine 307 promotes insulin sensitivity in mice. Cell Metabolism. 2010;11:84-92'},{id:"B79",body:'Brandon AE et al. Protein kinase C epsilon deletion in adipose tissue, but not in liver, improves glucose tolerance. Cell Metabolism. 2019;29:183-191.e7'},{id:"B80",body:'Deblon N et al. Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats. British Journal of Pharmacology. 2012;165:2325-2340'},{id:"B81",body:'Lamming DW et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012;335:1638-1643'},{id:"B82",body:'Friedman JE, Caro JF, Pories WJ, Azevedo JL Jr, Dohm GL. Glucose metabolism in incubated human muscle: Effect of obesity and non-insulin-dependent diabetes mellitus. Metabolism. 1994;43:1047-1054'},{id:"B83",body:'Shulman GI et al. Quantitation of muscle glycogen synthesis in normal subjects and subjects with noninsulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. The New England Journal of Medicine. 1990;322:223-228'},{id:"B84",body:'Baron AD, Laakso M, Brechtel G, Edelman SV. Reduced capacity and affinity of skeletal muscle for insulin-mediated glucose uptake in noninsulindependent diabetic subjects. Effects of insulin therapy. The Journal of Clinical Investigation. 1991;87:1186-1194'},{id:"B85",body:'Friedman JE et al. Restoration of insulin responsiveness in skeletal muscle of morbidly obese patients after weight loss. Effect on muscle glucose transport and glucose transporter GLUT4. The Journal of Clinical Investigation. 1992;89:701-705'},{id:"B86",body:'Meyer MM, Levin K, Grimmsmann T, BeckNielsen H, Klein HH. Insulin signalling in skeletal muscle of subjects with or without type II-diabetes and first degree relatives of patients with the disease. Diabetologia. 2002;45:813-822'},{id:"B87",body:'Kim YB, Nikoulina SE, Ciaraldi TP, Henry RR, Kahn BB. Normal insulin-dependent activation of Akt/protein kinase B, with diminished activation of phosphoinositide 3-kinase, in muscle in type 2 diabetes. The Journal of Clinical Investigation. 1999;104:733-741'},{id:"B88",body:'Ramos PA et al. Insulin-stimulated muscle glucose uptake and insulin signaling in lean and obese humans. The Journal of Clinical Endocrinology and Metabolism. 2020;106:e1631-e1646'},{id:"B89",body:'Vind BF et al. Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training. Diabetologia. 2011;54:157-167'},{id:"B90",body:'Caro JF et al. Insulin receptor kinase in human skeletal muscle from obese subjects with and without noninsulin dependent diabetes. The Journal of Clinical Investigation. 1987;79:1330-1337'},{id:"B91",body:'Garvey WT, Maianu L, Zhu JH, Hancock JA, Golichowski AM. Multiple defects in the adipocyte glucose transport system cause cellular insulin resistance in gestational diabetes. Heterogeneity in the number and a novel abnormality in subcellular localization of GLUT4 glucose transporters. Diabetes. 1993;42:1773-1785'},{id:"B92",body:'Ryder JW et al. Use of a novel impermeable biotinylated photolabeling reagent to assess insulin and hypoxia-stimulated cell surface GLUT4 content in skeletal muscle from type 2 diabetic patients. Diabetes. 2000;49:647-654'},{id:"B93",body:'Garvey WT et al. Evidence for defects in the trafficking and translocation of GLUT4 glucose transporters in skeletal muscle as a cause of human insulin resistance. The Journal of Clinical Investigation. 1998;101:2377-2386'},{id:"B94",body:'Gumà A, Zierath JR, Wallberg-Henriksson H, Klip A. Insulin induces translocation of GLUT-4 glucose transporters in human skeletal muscle. The American Journal of Physiology. 1995;268:E613-E622'},{id:"B95",body:'Dills WL Jr, McDonough GM, Kingsley PB. Glucose-stimulated protein synthesis in rat testis slices: Substrate specificity and effects of insulin and substrate analogs. Biology of Reproduction. 1981;25:466-474'},{id:"B96",body:'Chlouverakis C. The action of glucose on lipolysis. Metabolism. 1967;16:469-472'},{id:"B97",body:'Li J, Houseknecht KL, Stenbit AE, Katz EB, Charron MJ. Reduced glucose uptake precedes insulin signaling defects in adipocytes from heterozygous GLUT4 knockout mice. The FASEB Journal. 2000;14:1117-1125'},{id:"B98",body:'Shepherd PR, Kahn BB. Glucose transporters and insulin action—Implications for insulin resistance and diabetes mellitus. The New England Journal of Medicine. 1999;341:248-257'},{id:"B99",body:'Etgen GJ Jr et al. Exercise training reverses insulin resistance in muscle by enhanced recruitment of GLUT-4 to the cell surface. The American Journal of Physiology. 1997;272:E864-E869'},{id:"B100",body:'Klip A et al. Recruitment of GLUT-4 glucose transporters by insulin in diabetic rat skeletal muscle. Biochemical and Biophysical Research Communications. 1990;172:728-736'},{id:"B101",body:'Kennedy JW et al. Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes. Diabetes. 1999;48:1192-1197'},{id:"B102",body:'Ploug T, van Deurs B, Ai H, Cushman SW, Ralston E. Analysis of GLUT4 distribution in whole skeletal muscle fibers: Identification of distinct storage compartments that are recruited by insulin andmuscle contractions. The Journal of Cell Biology. 1998;142:1429-1446'},{id:"B103",body:'Stöckli J et al. The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle. Diabetes. 2015;64:1914-1922'},{id:"B104",body:'Humphrey SJ et al. Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2. Cell Metabolism. 2013;17:1009-1020'},{id:"B105",body:'Kjøbsted R et al. Intact regulation of the AMPK signaling network in response to exercise and insulin in skeletal muscle of male patients with type 2 diabetes: Illumination of AMPK activation in recovery from exercise. Diabetes. 2016;65:1219-1230'},{id:"B106",body:'Eguez L et al. Full intracellular retention of GLUT4 requires AS160 RabGTPase activating protein. Cell Metabolism. 2005;2:263-272'},{id:"B107",body:'Batista TM et al. A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes. Cell Metabolism. 2020;32:844-859.e5'},{id:"B108",body:'Boden G et al. Excessive caloric intake acutely causes oxidative stress, GLUT4 carbonylation, and insulin resistance in healthy men. Science Translational Medicine. 2015;7:304re7'},{id:"B109",body:'Hauck AK, Huang Y, Hertzel AV, Bernlohr DA. Adipose oxidative stress and protein carbonylation. The Journal of Biological Chemistry. 2019;294:1083-1088'},{id:"B110",body:'Snel M, Jonker JT, Schoones J, Lamb H, de Roos A, Pijl H, et al. Ectopic fat and insulin resistance: Pathophysiology and effect of diet and lifestyle interventions. International Journal of Endocrinology. 2012;983814:1-18'},{id:"B111",body:'Samuel VT, Petersen KF, Shulman GI. Lipid-induced insulin resistance: Unravelling the mechanism. The Lancet. 2010;375(9733):2267-2277'},{id:"B112",body:'Hammarstedt A, Graham TE, Kahn BB. Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells. Diabetology and Metabolic Syndrome. 2012;4:42'},{id:"B113",body:'Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE. Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia. 2000;43:1498-1506'},{id:"B114",body:'Abel ED et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature. 2001;409:729-733'},{id:"B115",body:'Vazirani RP et al. Disruption of adipose Rab10-dependent insulin signaling causes hepatic insulin resistance. Diabetes. 2016;65:1577-1589'},{id:"B116",body:'Poulsen P et al. Heritability of insulin secretion, peripheral and hepatic insulin action, and intracellular glucose partitioning in young and old Danish twins. Diabetes. 2005;54:275-283'},{id:"B117",body:'Flannick J et al. Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls. Nature. 2019;570:71-76'},{id:"B118",body:'Dimas AS et al. Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity. Diabetes. 2014;63:2158-2171'},{id:"B119",body:'Lotta LA et al. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nature Genetics. 2017;49:17-26'},{id:"B120",body:'MacKellar J, Cushman SW, Periwal V. Differential effects of thiazolidinediones on adipocyte growth and recruitment in Zucker fatty rats. PLoS One. 2009;4(12):e8196'},{id:"B121",body:'Levin K, Hother-Nielsen O, Henriksen JE, Beck-Nielsen H. Effects of troglitazone in young first-degree relatives of patients with type 2 diabetes. Diabetes Care. 2004;27:148-154'},{id:"B122",body:'Chaurasia B, Summers SA. Ceramides in metabolism: Key lipotoxic players. Annual Review of Physiology. 2021;83:303-330'},{id:"B123",body:'Boden G. Free fatty acids (FFA), a link between obesity and insulin resistance. Frontiers in Bioscience. 1998;3:d169-d175'},{id:"B124",body:'Pereira S et al. Resveratrol prevents insulin resistance caused by short-term elevation of free fatty acids in vivo. Applied Physiology, Nutrition, and Metabolism. 2015;40:1129-1136'},{id:"B125",body:'Felber JP, Vannotti A. Effects of fat infusion on glucose tolerance and insulin plasma levels. Medicina Experimentalis. International Journal of Experimental Medicine. 1964;10:153-156'},{id:"B126",body:'Wang L et al. Adipocyte Gi signaling is essential for maintaining whole-body glucose homeostasis and insulin sensitivity. Nature Communications. 2020;11:2995'},{id:"B127",body:'Karpe F, Dickmann JR, Frayn KN. Fatty acids, obesity, and insulin resistance: Time for a reevaluation. Diabetes. 2011;60:2441-2449'},{id:"B128",body:'Perseghin G, Ghosh S, Gerow K, Shulman GI. Metabolic defects in lean nondiabetic offspring of NIDDM parents: A cross-sectional study. Diabetes. 1997;46:1001-1009'},{id:"B129",body:'McQuaid SE et al. Downregulation of adipose tissue fatty acid trafficking in obesity: A driver for ectopic fat deposition? Diabetes. 2011;60:47-55'},{id:"B130",body:'Jeffery E, Church CD, Holtrup B, Colman L, Rodeheffer MS. Rapid depot-specific activation of adipocyte precursor cells at the onset of obesity. Nature Cell Biology. 2015;17:376-385'},{id:"B131",body:'Jeffery E et al. The adipose tissue microenvironment regulates depot-specific adipogenesis in obesity. Cell Metabolism. 2016;24:142-150'},{id:"B132",body:'Arner P, Arner E, Hammarstedt A, Smith U. Genetic predisposition for type 2 diabetes, but not for overweight/obesity, is associated with a restricted adipogenesis. PLoS One. 2011;6:e18284'},{id:"B133",body:'Ye J. Regulation of PPARgamma function by TNF-alpha. Biochemical and Biophysical Research Communications. 2008;374:405-408'},{id:"B134",body:'Shao M et al. De novo adipocyte differentiation from Pdgfrβ preadipocytes protects against pathologic visceral adipose expansion in obesity. Nature Communications. 2018;9:890'},{id:"B135",body:'Kim J-Y et al. Obesity-associated improvements in metabolic profile through expansion of adipose tissue. The Journal of Clinical Investigation. 2007;117:2621-2637'},{id:"B136",body:'Shepherd PR et al. Adipose cell hyperplasia and enhanced glucose disposal in transgenic mice overexpressing GLUT4 selectively in adipose tissue. The Journal of Biological Chemistry. 1993;268:22243-22246'},{id:"B137",body:'Carobbio S, Pellegrinelli V, Vidal-Puig A. Adipose tissue function and expandability as determinants of lipotoxicity and the metabolic syndrome. Advances in Experimental Medicine and Biology. 2017;960:161-196'},{id:"B138",body:'Czech MP. Mechanisms of insulin resistance related to white, beige, and brown adipocytes. Molecular Metabolism. 2020;34:27-42'},{id:"B139",body:'Zhang Y et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425-432'},{id:"B140",body:'Kahn CR, Wang G, Lee KY. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. The Journal of Clinical Investigation. 2019;129:3990-4000'},{id:"B141",body:'Friedman JM. Leptin and the endocrine control of energy balance. Nature Metabolism. 2019;1:754-764'},{id:"B142",body:'Blüher M et al. Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: Associations with metabolic parameters and insulin resistance and regulation by physical training. The Journal of Clinical Endocrinology and Metabolism. 2006;91:2310-2316'},{id:"B143",body:'Meyer LK, Ciaraldi TP, Henry RR, Wittgrove AC, Phillips SA. Adipose tissue depot and cell size dependency of adiponectin synthesis and secretion in human obesity. Adipocytes. 2013;2:217-226'},{id:"B144",body:'Yamauchi T et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nature Medicine. 2007;13:332-339'},{id:"B145",body:'Chen Z et al. Effects of adiponectin on T2DM and glucose homeostasis: A mendelian randomization study. Diabetes, Metabolic Syndrome and Obesity. 2020;13:1771-1784'},{id:"B146",body:'Ortega Moreno L et al. Evidence of a causal relationship between high serum adiponectin levels and increased cardiovascular mortality rate in patients with type 2 diabetes. Cardiovascular Diabetology. 2016;15:17'},{id:"B147",body:'Yore MM et al. Discovery of a class of endogenous mammalian lipids with anti-diabetic and antiinflammatory effects. Cell. 2014;159:318-332'},{id:"B148",body:'Mori MA, Ludwig RG, Garcia-Martin R, Brandão BB, Kahn CR. Extracellular miRNAs: From biomarkers to mediators of physiology and disease. Cell Metabolism. 2019;30(4):656-673'},{id:"B149",body:'Agbu P, Carthew RW. MicroRNA-mediated regulation of glucose and lipid metabolism. Nature Reviews. Molecular Cell Biology. 2021;22:425-438'},{id:"B150",body:'Crewe C, An YA, Scherer PE. The ominous triad of adipose tissue dysfunction: Inflammation, fibrosis, and impaired angiogenesis. The Journal of Clinical Investigation. 2017;127:74-82'},{id:"B151",body:'Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860-867'},{id:"B152",body:'Kammoun HL, Kraakman MJ, Febbraio MA. Adipose tissue inflammation in glucose metabolism. Reviews in Endocrine & Metabolic Disorders. 2014;15:31-44'},{id:"B153",body:'McNelis JC, Olefsky JM. Macrophages, immunity, and metabolic disease. Immunity. 2014;41:36-48'},{id:"B154",body:'Mathis D. Immunological goings-on in visceral adipose tissue. Cell Metabolism. 2013;17:851-859'},{id:"B155",body:'Hotamisligil GS. Inflammation, metaflammation and immunometabolic disorders. Nature. 2017;542:177-185'},{id:"B156",body:'Wu H, Ballantyne CM. Metabolic inflammation and insulin resistance in obesity. Circulation Research. 2020;126:1549-1564'},{id:"B157",body:'Krogh-Madsen R, Plomgaard P, Møller K, Mittendorfer B, Pedersen BK. Influence of TNF-alpha and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans. American Journal of Physiology. Endocrinology and Metabolism. 2006;291:E108-E114'},{id:"B158",body:'Kriketos AD et al. Inflammation, insulin resistance, and adiposity: A study of first-degree relatives of type 2 diabetic subjects. Diabetes Care. 2004;27:2033-2040'},{id:"B159",body:'Shimobayashi M et al. Insulin resistance causes inflammation in adipose tissue. The Journal of Clinical Investigation. 2018;128:1538-1550'},{id:"B160",body:'Lee YS et al. Inflammation is necessary for long-term but not short-term high-fat diet-induced insulin resistance. Diabetes. 2011;60:2474-2483'},{id:"B161",body:'Rafiq S et al. Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes. Diabetologia. 2008;51:2205-2213'},{id:"B162",body:'Everett BM et al. Anti-inflammatory therapy with canakinumab for the prevention and management of diabetes. Journal of the American College of Cardiology. 2018;71:2392-2401'},{id:"B163",body:'Ridker PM et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. The New England Journal of Medicine. 2017;377:1119-1131'},{id:"B164",body:'Smith U, Li Q , Rydén M, Spalding KL. Cellular senescence and its role in white adipose tissue. International Journal of Obesity. 2021;45:934-943'},{id:"B165",body:'WernstedtAsterholm I et al. Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metabolism. 2014;20:103-118'},{id:"B166",body:'Cox AR, Chernis N, Masschelin PM, Hartig SM. Immune cells gate white adipose tissue expansion. Endocrinology. 2019;160:1645-1658'},{id:"B167",body:'Chaurasia B, Summers SA. Ceramides—lipotoxic inducers of metabolic disorders. Trends in Endocrinology and Metabolism. 2015;26:538-550'},{id:"B168",body:'Luukkonen PK et al. Hepatic ceramides dissociate steatosis and insulin resistance in patients with non-alcoholic fatty liver disease. Journal of Hepatology. 2016;64:1167-1175'},{id:"B169",body:'Kolak M et al. Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity. Diabetes. 2007;56:1960-1968'},{id:"B170",body:'Coen PM et al. Reduced skeletal muscle oxidative capacity and elevated ceramide but not diacylglycerol content in severe obesity. Obesity. 2013;21:2362-2371'},{id:"B171",body:'Turpin SM et al. Obesity-induced CerS6-dependent C16:0 ceramide production promotes weight gain and glucose intolerance. Cell Metabolism. 2014;20:678-686'},{id:"B172",body:'Stöckli J et al. Metabolomic analysis of insulin resistance across different mouse strains and diets. The Journal of Biological Chemistry. 2017;292:19135-19145'},{id:"B173",body:'Siddique MM et al. Ablation of dihydroceramide desaturase 1, a therapeutic target for the treatment of metabolic diseases, simultaneously stimulates anabolic and catabolic signaling. Molecular and Cellular Biology. 2013;33(11):2353-2369'},{id:"B174",body:'Raichur S et al. CerS2 haploinsufficiency inhibits β-oxidation and confers susceptibility to diet-induced steatohepatitis and insulin resistance. Cell Metabolism. 2014;20:687-695'},{id:"B175",body:'Chaurasia B et al. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science. 2019;365:386-392'},{id:"B176",body:'Chavez JA et al. A role for ceramide, but not diacylglycerol, in the antagonism of insulin signal transduction by saturated fatty acids. The Journal of Biological Chemistry. 2003;278:10297-10303'},{id:"B177",body:'Villa NY et al. Sphingolipids function as downstream effectors of a fungal PAQR. Molecular Pharmacology. 2009;75:866-875'},{id:"B178",body:'Mente A et al. Causal relationship between adiponectin and metabolic traits: A Mendelian randomization study in a multiethnic population. PLoS One. 2013;8:e66808'},{id:"B179",body:'Nawrocki AR et al. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists. The Journal of Biological Chemistry. 2006;281:2654-2660'},{id:"B180",body:'Cazzolli R, Carpenter L, Biden TJ, Schmitz-Peiffer C. A role for protein phosphatase 2A-like activity, but not atypical protein kinase Czeta, in the inhibition of protein kinase B/Akt and glycogen synthesis by palmitate. Diabetes. 2001;50:2210-2218'},{id:"B181",body:'Fox TE et al. Ceramide recruits and activates protein kinase C zeta (PKC zeta) within structured membrane microdomains. The Journal of Biological Chemistry. 2007;282:12450-12457'},{id:"B182",body:'Lyu K et al. A membrane-bound diacylglycerol species induces PKCε-mediated hepatic insulin resistance. Cell Metabolism. 2020;32:654-664.e5'},{id:"B183",body:'Lyu K et al. Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2- diacylglycerol/PKCε/insulin receptor Thr1160 phosphorylation. JCI Insight. 2021;6:e139946'},{id:"B184",body:'Gassaway BM et al. PKCε contributes to lipid-induced insulin resistance through cross talk with p70S6K and through previously unknown regulators of insulin signaling. Proceedings of the National Academy of Sciences of the United States of America. 2018;115:E8996-E9005'},{id:"B185",body:'Perreault L et al. Intracellular localization of diacylglycerols and sphingolipids influences insulin sensitivity and mitochondrial function in human skeletal muscle. JCI Insight. 2018;3:e96805'},{id:"B186",body:'Gonzalez-Franquesa A, Patti M-E. Insulin resistance and mitochondrial dysfunction. Advances in Experimental Medicine and Biology. 2017;982:465-520'},{id:"B187",body:'Sangwung P, Petersen KF, Shulman GI, Knowles JW. Mitochondrial dysfunction, insulin resistance, and potential genetic implications. Endocrinology. 2020;161:bqaa017'},{id:"B188",body:'Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 2006;440:944-948'},{id:"B189",body:'Fisher-Wellman KH, Neufer PD. Linking mitochondrial bioenergetics to insulin resistance via redox biology. Trends in Endocrinology and Metabolism. 2012;23:142-153'},{id:"B190",body:'Hoehn KL et al. Insulin resistance is a cellular antioxidant defense mechanism. Proceedings of the National Academy of Sciences of the United States of America. 2009;106:17787-17792'},{id:"B191",body:'Anderson EJ et al. Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. The Journal of Clinical Investigation. 2009;119:573-581'},{id:"B192",body:'Ingram KH et al. Skeletal muscle lipid peroxidation and insulin resistance in humans. Journal of Clinical Endocrinology and Metabolism. 2012;97:E1182-E1186'},{id:"B193",body:'Duplain H et al. Stimulation of peroxynitrite catalysis improves insulin sensitivity in high fat diet-fed mice. The Journal of Physiology. 2008;586:4011-4016'},{id:"B194",body:'Fazakerley DJ et al. Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation. The Journal of Biological Chemistry. 2018;293:7315-7328'},{id:"B195",body:'Boveris A, Oshino N, Chance B. The cellular production of hydrogen peroxide. The Biochemical Journal. 1972;128:617-630'},{id:"B196",body:'Rees-Milton KJ et al. Statin use is associated with insulin resistance in participants of the Canadian multicentre osteoporosis study. Journal of the Endocrine Society. 2020;4:bvaa057'},{id:"B197",body:'Koves TR et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metabolism. 2008;7:45-56'},{id:"B198",body:'Di Paola M, Cocco T, Lorusso M. Ceramide interaction with the respiratory chain of heart mitochondria. Biochemistry. 2000;39:6660-6668'},{id:"B199",body:'Smith ME et al. Mitochondrial fission mediates ceramide-induced metabolic disruption in skeletal muscle. The Biochemical Journal. 2013;456:427-439'},{id:"B200",body:'Novgorodov SA et al. Novel pathway of ceramide production in mitochondria: Thioesterase and neutral ceramidase produce ceramide from sphingosine and acyl-CoA. The Journal of Biological Chemistry. 2011;286:25352-25362'},{id:"B201",body:'vonHaefen C et al. Ceramide induces mitochondrial activation and apoptosis via a Bax-dependent pathway in human carcinoma cells. Oncogene. 2002;21:4009-4019'},{id:"B202",body:'Ye R, Onodera T, Scherer PE. Lipotoxicity and cell maintenance in obesity and type 2 diabetes. Journal of the Endocrine Society. 2019;3:617-631'},{id:"B203",body:'Turpin SM et al. Examination of ‘lipotoxicity’ in skeletal muscle of high-fat fed 0. The Journal of Physiology. 2009;587:1593-1605'},{id:"B204",body:'Kim Y-R et al. Hepatic triglyceride accumulation via endoplasmic reticulum stress-induced SREBP-1 activation is regulated by ceramide synthases. Experimental & Molecular Medicine. 2019;51:1-16'},{id:"B205",body:'Boslem E et al. A lipidomic screen of palmitate-treated MIN6 β-cells links sphingolipid metabolites with endoplasmic reticulum (ER) stress and impaired protein trafficking. The Biochemical Journal. 2011;435:267-276'},{id:"B206",body:'Flamment M, Hajduch E, Ferré P, Foufelle F. New insights into ER stress-induced insulin resistance. Trends in Endocrinology and Metabolism. 2012;23:381-390'},{id:"B207",body:'Sumitomo M et al. Protein kinase Cdelta amplifies ceramide formation via mitochondrial signaling in prostate cancer cells. The Journal of Clinical Investigation. 2002;109:827-836'},{id:"B208",body:'Lee H-Y et al. Mitochondrial-targeted catalase protects against high-fat diet-induced muscle insulin resistance by decreasing intramuscular lipid accumulation. Diabetes. 2017;66:2072-2081'},{id:"B209",body:'Riojas-Hernández A et al. Enhanced oxidative stress sensitizes the mitochondrial permeability transition pore to opening in heart from Zucker fa/fa rats with type 2 diabetes. Life Sciences. 2015;141:32-43'},{id:"B210",body:'Taddeo EP et al. Opening of the mitochondrial permeability transition pore links mitochondrial dysfunction to insulin resistance in skeletal muscle. Molecular Metabolism. 2014;3:124-134'},{id:"B211",body:'Cho J et al. Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance. Nature Communications. 2017;8:14477'},{id:"B212",body:'O’Neill BT et al. Differential role of insulin/IGF-1 receptor signaling in muscle growth and glucose homeostasis. Cell Reports. 2015;11:1220-1235'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Atamjit Singh",address:null,affiliation:'
Department of Pharmaceutical Sciences, Guru Nanak Dev University, India
Department of Pharmaceutical Sciences, Guru Nanak Dev University, India
Drug and Pollution Testing Lab, Guru Nanak Dev University, India
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Red maize in particular owes its coloring to a type of polyphenolic compounds known as anthocyanins. The aim of this study was to determine the profile anthocyanin of red maize, as well as their antiproliferative activity on prostate cancer cell line DU145. Three samples of red maize were analyzed. Total polyphenols, monomeric anthocyanins, antioxidant activity by DDPH and FRAP were evaluated. The sample of red maize with the highest levels of total polyphenols and monomeric anthocyanins was selected, and its anthocyanin fraction was analyzed by HPLC-ESI-MS. Twenty compounds were detected in the anthocyanin profile, and from these, 12 anthocyanins derived of cyanidin were identified. MTT assay was used to determine the antiproliferative activity of the anthocyanin fraction from red maize at different concentrations (7–1000 μg/mL), and a significant antiproliferative activity was observed at 1000 μg/mL. Microscopy analysis showed that the anthocyanin fraction of red maize induced apoptosis in cell lines DU145. This is the first report showing that anthocyanin fraction of red maize possess antiproliferative activity in the DU145 cell line.",signatures:"Mónica Herrera-Sotero, Francisco González-Cortés, Hugo García-\nGalindo, Enrique Juarez-Aguilar, Mauricio Rodríguez Dorantes, José\nChávez-Servia, Rosa Oliart-Ros and Rosa Guzmán-Gerónimo",authors:[{id:"173795",title:"Prof.",name:"Rosamaria",surname:"Oliart",fullName:"Rosamaria Oliart",slug:"rosamaria-oliart",email:"roliart@itver.edu.mx"},{id:"195746",title:"Prof.",name:"Rosa",surname:"Guzmán-Gerónimo",fullName:"Rosa Guzmán-Gerónimo",slug:"rosa-guzman-geronimo",email:"roguzman@uv.mx"},{id:"195752",title:"Dr.",name:"Jose",surname:"Chavez-Servia",fullName:"Jose Chavez-Servia",slug:"jose-chavez-servia",email:"jchavezservia1@yahoo.com"},{id:"200086",title:"Dr.",name:"Mónica",surname:"Herrera-Sotero",fullName:"Mónica Herrera-Sotero",slug:"monica-herrera-sotero",email:"monycpo@hotmail.com"},{id:"200090",title:"Dr.",name:"Hugo",surname:"García-Galindo",fullName:"Hugo García-Galindo",slug:"hugo-garcia-galindo",email:"hugosgg@gmail.com"},{id:"200096",title:"MSc.",name:"Francisco",surname:"González-Cortés",fullName:"Francisco González-Cortés",slug:"francisco-gonzalez-cortes",email:"rafaelglez@hotmail.com"},{id:"200097",title:"Dr.",name:"Enrique",surname:"Juárez-Aguilar",fullName:"Enrique Juárez-Aguilar",slug:"enrique-juarez-aguilar",email:"enaguilar@uv.mx"},{id:"200098",title:"Dr.",name:"Mauricio",surname:"Rodríguez-Dorantes",fullName:"Mauricio Rodríguez-Dorantes",slug:"mauricio-rodriguez-dorantes",email:"mrodriguez@inmegen.gob.mx"}],book:{id:"5828",title:"Flavonoids",slug:"flavonoids-from-biosynthesis-to-human-health",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"172326",title:"Dr.",name:"Latifa",surname:"Chebil",slug:"latifa-chebil",fullName:"Latifa Chebil",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Henri Poincaré Institute",institutionURL:null,country:{name:"France"}}},{id:"172358",title:"Prof.",name:"Mohamed",surname:"Ghoul",slug:"mohamed-ghoul",fullName:"Mohamed Ghoul",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"190870",title:"Dr.",name:"Agustín G.",surname:"Asuero",slug:"agustin-g.-asuero",fullName:"Agustín G. 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If your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
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IMPORTANT: You must be a member or grantee of the listed funders in order to apply for their Open Access publication funds. Do not attempt to contact the funders if this is not the case.
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UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
Wellcome Trust (Funding available only to Wellcome-funded researchers/grantees)
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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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The model parameters deciphered here are the amplitude coefficient (k), horizontal location (x0), depth of the body (z), and shape (q). Inversion of the model parameter suggests that constraining the horizontal location and the shape factor offers the most reliable results. Investigation of convergence rate, histogram, and cross-plot examination suggest that the interpretation method developed for the self-potential anomalies is stable and the model parameters are within the estimated ambiguity. Inversion of synthetic noise-free and noise-corrupted data for single structures and multiple structures in addition to real field information exhibits the viability of the method. The model parameters estimated by the present technique were in good agreement with the real parameters. The method has been used to invert two field examples (Sulleymonkoy anomaly, Ergani, Turkey, Senneterre area of Quebec, Canada) with application of subsurface mineralized bodies. 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In fact, under some specific conditions the NCMs could be used either as effective adsorbent material or alternative source of minerals. This chapter presents an outline of a general review of factors that affect the application ability of NCMs and a descriptive analysis of NH4+ and REE adsorption behavior and extraction of rare earth elements (REE) by an ion-exchange with NH4+ ions onto NCMs. Clays and NCMs both effectively remove various contaminants from aqueous solution and serve as alternative sources of minerals, as extensively discussed in this chapter. This review compiles thorough literature of current research and highlights the key findings of adsorption (NH4+ and REE) that use different NCMs as adsorbents or alternative sources of minerals (i.e., REE). The review confirmed that NCMs excellently remove different cations pollutants and have significant potential as alternative source of REE. However, modification and further development of NCMs applications for getting the best adsorption and the best extraction of REE onto NCMs, which would enhance pollution control and leaching system is still needed.",book:{id:"7315",slug:"minerals",title:"Minerals",fullTitle:"Minerals"},signatures:"Aref Alshameri, Xinghu Wei, Hailong Wang, Yang Fuguo, Xin Chen, Hongping He, Chunjie Yan and Feng Xu",authors:[{id:"172947",title:"Prof.",name:"Xin",middleName:null,surname:"Chen",slug:"xin-chen",fullName:"Xin Chen"},{id:"250327",title:"Dr.",name:"Aref",middleName:null,surname:"Alshameri",slug:"aref-alshameri",fullName:"Aref Alshameri"},{id:"306625",title:"Dr.",name:"Aref",middleName:null,surname:"Alshameri",slug:"aref-alshameri",fullName:"Aref Alshameri"},{id:"306656",title:"Prof.",name:"Fuguo",middleName:null,surname:"Yang",slug:"fuguo-yang",fullName:"Fuguo Yang"},{id:"306658",title:"Dr.",name:"Wei",middleName:null,surname:"Xinghu",slug:"wei-xinghu",fullName:"Wei Xinghu"},{id:"306660",title:"Prof.",name:"Wang",middleName:null,surname:"Hailong",slug:"wang-hailong",fullName:"Wang Hailong"},{id:"306664",title:"Prof.",name:"Yan",middleName:null,surname:"Chunjie",slug:"yan-chunjie",fullName:"Yan Chunjie"},{id:"306665",title:"Dr.",name:"Xu",middleName:null,surname:"Feng",slug:"xu-feng",fullName:"Xu Feng"},{id:"306671",title:"Prof.",name:"He",middleName:null,surname:"Hongping",slug:"he-hongping",fullName:"He Hongping"}]}],mostDownloadedChaptersLast30Days:[{id:"71052",title:"Enhanced Humidity Sensing Response in Eu3+-Doped Iron-Rich CuFe2O4: A Detailed Study of Structural, Microstructural, Sensing, and Dielectric Properties",slug:"enhanced-humidity-sensing-response-in-eu-sup-3-sup-doped-iron-rich-cufe-sub-2-sub-o-sub-4-sub-a-deta",totalDownloads:596,totalCrossrefCites:7,totalDimensionsCites:7,abstract:"The CuFe(2−x)EuxO4 (where x = 0.00, 0.01, 0.02, 0.03) nanoparticles are synthesized by solution combustion method. The influence of Eu3+ on the structural, morphological, dielectrical, and humidity sensing study is recorded. The XRD pattern peaks of the as-prepared CuFe(2−x)EuxO4 (where x = 0.00, 0.01, 0.02, 0.03) nanoparticle confirm the polycrystalline spinel cubic structure with a small amount of CuO impurity phase at 38.87° and 48.96°. Surface morphology of the samples was studied by scanning electron microscope (SEM) images of the nanoparticles, and their respective average grain size was estimated using Image software. Chemical composition of all prepared samples was analyzed by EDS spectra. The dielectric parameters of AC conductivity, electric modulus, and impedance of the samples were measured over a range of frequencies from 0.1 KHz to 1 MHz at room temperature. Europium-doped copper ferrite samples showed good humidity sensing response, response and recover times, and stability over a %RH range of 11–91%. These types of samples are very useful for sensor application, battery applications, electronic applications, and automotive applications.",book:{id:"9247",slug:"mineralogy-significance-and-applications",title:"Mineralogy",fullTitle:"Mineralogy - Significance and Applications"},signatures:"I.C. Sathisha, K. Manjunatha, V. Jagadeesha Angadi, B. Chethan, Y.T. Ravikiran, Vinayaka K. Pattar, S.O. Manjunatha and Shidaling Matteppanavar",authors:[{id:"266255",title:"Dr.",name:"Veerabhadrappa",middleName:null,surname:"Jagadeesha Angadi",slug:"veerabhadrappa-jagadeesha-angadi",fullName:"Veerabhadrappa Jagadeesha Angadi"},{id:"321561",title:"Dr.",name:"I.C.",middleName:null,surname:"Sathisha",slug:"i.c.-sathisha",fullName:"I.C. Sathisha"},{id:"321562",title:"Dr.",name:"K.",middleName:null,surname:"Manjunatha",slug:"k.-manjunatha",fullName:"K. Manjunatha"},{id:"321564",title:"Dr.",name:"B.",middleName:null,surname:"Chethan",slug:"b.-chethan",fullName:"B. Chethan"},{id:"321565",title:"Dr.",name:"Y.T.",middleName:null,surname:"Ravikiran",slug:"y.t.-ravikiran",fullName:"Y.T. Ravikiran"},{id:"321566",title:"Dr.",name:"Vinayaka K.",middleName:null,surname:"Pattar",slug:"vinayaka-k.-pattar",fullName:"Vinayaka K. Pattar"},{id:"321567",title:"Dr.",name:"S.O.",middleName:null,surname:"Manjunatha",slug:"s.o.-manjunatha",fullName:"S.O. Manjunatha"},{id:"321568",title:"Dr.",name:"Shidaling",middleName:null,surname:"Matteppanavar",slug:"shidaling-matteppanavar",fullName:"Shidaling Matteppanavar"}]},{id:"65826",title:"Introductory Chapter: Mineral Exploration from the Point of View of Geophysicists",slug:"introductory-chapter-mineral-exploration-from-the-point-of-view-of-geophysicists",totalDownloads:1635,totalCrossrefCites:3,totalDimensionsCites:3,abstract:null,book:{id:"7315",slug:"minerals",title:"Minerals",fullTitle:"Minerals"},signatures:"Khalid S. Essa and Marc Munschy",authors:[{id:"102766",title:"Prof.",name:"Khalid S.",middleName:null,surname:"Essa",slug:"khalid-s.-essa",fullName:"Khalid S. Essa"},{id:"292929",title:"Prof.",name:"Marc",middleName:null,surname:"Munschy",slug:"marc-munschy",fullName:"Marc Munschy"}]},{id:"69811",title:"Chemical Synthesis and Characterization of Luminescent Iron Oxide Nanoparticles and Their Biomedical Applications",slug:"chemical-synthesis-and-characterization-of-luminescent-iron-oxide-nanoparticles-and-their-biomedical",totalDownloads:564,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The syntheses and characterizations of biocompatible luminescent magnetic iron oxide nanoparticles has drawn particular attention as diagnostic and drug delivery tools for treatment of cancer and many other diseases. This chapter focuses on the chemical synthetic methods, magnetic and luminescent properties, including the biomedical applications of iron oxide nanomaterials and luminescent magnetic iron oxide-based nanocomposite materials. The influences of functionalizing with short ligands such as dopamine and L-cysteine on the magnetic properties of synthesized nanoparticles are described. The chapter contains some data on necessary reagents and protocols for bioconjugation aimed at cell culture and step by step the MTT assays used to evaluate cytotoxicity are also presented. In the final section of the chapter, we focus on the biomedical applications specifically for diagnosis and treatment of breast cancer treatment. This chapter also investigates the application of various characterization techniques for analysis of the structural, optical and magnetic properties of the iron oxide nanoparticles and as their nanocomposites.",book:{id:"9247",slug:"mineralogy-significance-and-applications",title:"Mineralogy",fullTitle:"Mineralogy - Significance and Applications"},signatures:"Martin Onani, Leandre Brandt and Zuraan Paulsen",authors:[{id:"258023",title:"Dr.",name:"Martin",middleName:null,surname:"Onani",slug:"martin-onani",fullName:"Martin Onani"},{id:"302723",title:"Dr.",name:"Leandré Bianca",middleName:null,surname:"Brandt",slug:"leandre-bianca-brandt",fullName:"Leandré Bianca Brandt"},{id:"302725",title:"MSc.",name:"Zuraan",middleName:null,surname:"Paulsen",slug:"zuraan-paulsen",fullName:"Zuraan Paulsen"}]},{id:"27429",title:"An Introduction to Mineralogy",slug:"an-introduction-to-mineralogy",totalDownloads:6621,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"1600",slug:"an-introduction-to-the-study-of-mineralogy",title:"An Introduction to the Study of Mineralogy",fullTitle:"An Introduction to the Study of Mineralogy"},signatures:"Cumhur Aydinalp",authors:[{id:"98959",title:"Prof.",name:"Cumhur",middleName:"---",surname:"Aydinalp",slug:"cumhur-aydinalp",fullName:"Cumhur Aydinalp"}]},{id:"27435",title:"A Review of Pathological Biomineral Analysis Techniques and Classification Schemes",slug:"a-review-of-pathological-biomineral-analysis-techniques-and-classification-schemes",totalDownloads:4303,totalCrossrefCites:1,totalDimensionsCites:6,abstract:null,book:{id:"1600",slug:"an-introduction-to-the-study-of-mineralogy",title:"An Introduction to the Study of Mineralogy",fullTitle:"An Introduction to the Study of Mineralogy"},signatures:"Maria Luigia Giannossi and Vito Summa",authors:[{id:"101919",title:"PhD.",name:"Maria Luigia",middleName:null,surname:"Giannossi",slug:"maria-luigia-giannossi",fullName:"Maria Luigia Giannossi"},{id:"108348",title:"Dr.",name:"Vito",middleName:null,surname:"Summa",slug:"vito-summa",fullName:"Vito Summa"}]}],onlineFirstChaptersFilter:{topicId:"651",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81626",title:"Use of Natural Safiot Clay for the Removal of Chemical Substances from Aqueous Solutions by Adsorption: A Combined Experimental and Theoretical Study",slug:"use-of-natural-safiot-clay-for-the-removal-of-chemical-substances-from-aqueous-solutions-by-adsorpti",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.101605",abstract:"The main objective of this work was to investigate the potential of Natural Safiot Clay (NSC), as an adsorbent for the removal of two cationic dyes such as Basic Blue 9 (BB9) and Basic Yellow 28 (BY28) from single and binary systems in aqueous solutions. For this, the effects of three factors controlling the adsorption process, such as initial dye concentration, adsorbent dose, and initial pH on the adsorption extent, were investigated and examined. The natural safiot clay was characterized using the following technique: energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), DRX, and Fourier transform infrared (FT-IR) and pH of the point of zero charge (pHZPC). Energy-dispersive X-ray spectroscopy results indicate high percentages of Silica and Alumina. FT-IR spectrum identified kaolinite as the major mineral phase in the presence of quartz, calcite, and dolomite. The quantum theoretical study confirms the experimental results, through the study of the global and local reactivity and the electrophilicity power of the dyes. The electrophilicity power of dyes affects the removal efficiency. The theoretical study proves that BB9 (ω = 6.178) is more electrophilic than BY28 (ω = 2.480) and more interactions with surface sites. The results of the molecular dynamics simulation indicate that the dyes are adsorbed parallel to the surface of natural Safi clay (kaolinite), implying the strong interaction with the kaolinite atoms. All the results of quantum chemistry calculations and simulations of molecular dynamics are in perfect agreement with the results of the experimental study.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Aziz El Kassimi, Mohammadine El Haddad, Rachid Laamari, Mamoune El Himri, Youness Achour and Hicham Yazid"},{id:"80866",title:"Normative Mineralogy Especially for Shales, Slates, and Phyllites",slug:"normative-mineralogy-especially-for-shales-slates-and-phyllites",totalDownloads:44,totalDimensionsCites:0,doi:"10.5772/intechopen.102346",abstract:"First, an insight into normative mineralogy and the most important methods for calculating the standard or norm minerals, such as the CIPW norm, is given. This is followed by a more detailed explanation of “slatenorm” and “slatecalculation” for low and very low metamorphic rocks, such as phyllites, slates, and shales. They are particularly suitable for fine-grained rocks where the mineral content is difficult to determine. They enable the determination of a virtual mineral inventory from full chemical analysis, including the values of carbon dioxide (CO2), carbon (C), and sulfur (S). The determined norm or standard minerals include the minerals—feldspars, carbonates, micas, hydro-micas, chlorites, ore minerals, and quartz. The advantages of slatenorm and slatecalculation compared to other methods for calculating normal minerals of sedimentary rocks are discussed.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Hans Wolfgang Wagner"},{id:"80770",title:"Mg-Ilmenite from Kimberlites, Its Origin",slug:"mg-ilmenite-from-kimberlites-its-origin",totalDownloads:57,totalDimensionsCites:0,doi:"10.5772/intechopen.102676",abstract:"The main regularities of the saturation of kimberlite rocks with the accessory mineral Mg-ilmenite (Ilm), the peculiarities of the distribution of Ilm compositions in individual pipes, in different clusters of pipes, in diamondiferous kimberlite fields, are considered as the example of studies carried out within the Yakutian kimberlite province (Siberian Craton). Interpretation of different crystallization trends in MgO-Cr2O3 coordinates (conventionally named “Haggerty’s parabola”, “Steplike”, “Hockey stick”, as well as the peculiarities of heterogeneity of individual zonal and polygranular Ilm macrocrysts made it possible to propose a three-stage model of crystallization Ilm: (1) Mg-Cr poor ilmenite crystallizing from a primitive asthenospheric melt; (2) Continuing crystallization in the lithospheric contaminated melt by MgO and Cr2O3; (3) Ilmenite subsequently underwent sub-solidus recrystallization in the presence of an evolved kimberlite melt under increasing oxygen fugacity (ƒO2) conditions.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Sergey I. Kostrovitsky"},{id:"80553",title:"Investigation of Accessory Minerals from the Blatná Granodiorite Suite, Bohemian Massif, Czech Republic",slug:"investigation-of-accessory-minerals-from-the-blatn-granodiorite-suite-bohemian-massif-czech-republic",totalDownloads:48,totalDimensionsCites:0,doi:"10.5772/intechopen.102628",abstract:"The Central Bohemian magmatic complex belongs to the Central European Variscan belt. The granitic rocks of this plutonic complex are formed by several suites of granites, granodiorites, and tonalites, together with small bodies of gabbros, gabbro diorites, and diorites. The granodiorites of the Blatná suite are high-K, calc-alkaline to shoshonitic, and metaluminous to slightly peraluminous granitic rocks. Compared to the common I-type granites, granodiorites of the Blatná suite are enriched in Mg (1.0–3.4 wt.% MgO), Ba (838–2560 ppm), Sr. (257–506 ppm), and Zr (81–236 ppm). For granodiorites of the Blatná suite is assemblage of apatite, zircon, titanite, and allanite significant. Zircon contains low Hf concentrations (1.1–1.7 wt.% HfO2). The composition of titanite ranges from 83 to 92 mol.% titanite end-member. Allanite is relatively Al-poor and displays Feox. ratio 0.2–0.5.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Miloš René"},{id:"80423",title:"Minerals as Prebiotic Catalysts for Chemical Evolution towards the Origin of Life",slug:"minerals-as-prebiotic-catalysts-for-chemical-evolution-towards-the-origin-of-life",totalDownloads:106,totalDimensionsCites:0,doi:"10.5772/intechopen.102389",abstract:"A transition from geochemistry to biochemistry has been considered as a necessary step towards the emergence of primordial life. Nevertheless, how did this transition occur is still elusive. The chemistry underlying this transition is likely not a single event, but involves many levels of creation and reconstruction, finally reaching the molecular, structural, and functional buildup of complexity. Among them, one apparent question is: how the biochemical catalytic system emerged from the mineral-based geochemical system? Inspired by the metal–ligand structures in metalloenzymes, many researchers have proposed that transition metal sulfide minerals could have served as structural analogs of metalloenzymes for catalyzing prebiotic redox conversions. This assumption has been tested and verified to some extent by several studies, which focused on using Earth-abundant transition metal sulfides as catalysts for multi-electron C and N conversions. The progress in this field will be introduced, with a focus on the CO2 fixation and ammonia synthesis from nitrate/nitrite reduction and N2 reduction. Recently developed methods for screening effective mineral catalysts were also reviewed.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Yamei Li"},{id:"80338",title:"Ionic Conductivity of Strontium Fluoroapatites Co-doped with Lanthanides",slug:"ionic-conductivity-of-strontium-fluoroapatites-co-doped-with-lanthanides",totalDownloads:54,totalDimensionsCites:0,doi:"10.5772/intechopen.102410",abstract:"Britholites derivatives of apatite’s that contain lanthanium and neodymium in the serial compounds Sr8La2−xNdx(PO4)4(SiO4)2F2 with 0 ≤ x ≤ 2 were subject of the present investigation. The solid state reaction was the route of preparing these materials. Several techniques were employed for the analysis and characterization of the synthesized powders. The chemical analysis results indicated that molar ratio Sr+La+NdP+Si was of about 1.67 value of a stoichiometric powder. The X-ray diffraction data showed single-phase apatites crystallizing in hexagonal structure with P63/m space group were successively obtained. Moreover, the substitution of lanthanium by neodymium in strontium phosphosilicated fluorapatite was total. This was confirmed by the a and c lattice parameters contraction when (x) varies coherently to the sizes of the two cations. The infrared spectroscopy and the 31P NMR (MAS) exhibited the characteristic bands of phosphosilicated fluorapatite. The pressureless sintering of the material achieved a maximum of 89% relative density. The sintered specimens indicated that the Nd content as well as the heating temperature affected the ionic conduction of the materials and the maximum was 1.73 × 10−6 S cm−1 obtained at 1052 K for x = 2.",book:{id:"11137",title:"Mineralogy",coverURL:"https://cdn.intechopen.com/books/images_new/11137.jpg"},signatures:"Khouloud Kthiri, Mohammed Mehnaoui, Samira Jebahi, Khaled Boughzala and Mustapha Hidouri"}],onlineFirstChaptersTotal:10},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. 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He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. 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She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. 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Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. 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His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. 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He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. 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