Differences between gamma knife, LINAC, and cyberknife.
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Stereotactic radiosurgery of the brain using the Gamma Knife or a Linear accelerator (LINAC) is a well-established and very effective therapy for brain metastases, arteriovenous malformations, and benign skull base tumors [1, 2]. The treatment utilizes differences in the biological sensitivity and repair capability of normal and pathologic tissue [3]. Stereotactic principles are used for calculating the radiation field. The patient wears a stereotactic head frame and undergoes a computed tomography (CT), which is subsequently fused with a preexisting magnetic resonance (MRI) scan, or an MRI is performed in the stereotactic head frame, the disadvantage being that there are often distortions of the magnetic field [4]. However, most lesions are better demonstrated on MRI scans. The aim of dose planning is to deliver a maximal dose to the tumor, while minimizing radiation dose to healthy brain structures. This is accomplished with conforming the radiation to the target and applying steep dose gradients [1, 2].
LINAC-based radiosurgery and radiation therapy devices accelerate electrons, and the electron beam is aimed at a heavy metal alloy target [1]. The resulting interactions between the electrons and the target produce photons, which can be collimated and focused on a patient. Multiple radiation beams are applied, each of which has its own entrance and exit points, while all are directed at the same target where they cross each other [1]. In LINAC radiosurgery and fractionated radiation therapy, both the gantry and the treatment table rotate around the isocenter of the lesion for accurate delivery of the multiple beams [1]. The single radiosurgery radiation dose prescribed in LINAC-based radiosurgery for benign skull base tumors is commonly 10–17.5 Gy [1, 4, 5, 6]. Notably, in case of lesions adjacent to radiosensitive structures, fractionation is the preferred method of delivery, in which case different dose regimes apply [1, 7, 8]. In contrast to the Gamma Knife, LINAC offers the option of dose fractionation. Fractionated stereotactic radiation therapy (FSRT) utilizes the principles of conventional fractionation while taking advantage of stereotactic dosimetric techniques to conform the radiation to the tumor target. It is particularly suitable for treating skull base tumors, close to eloquent structures, such as the pituitary gland and optic nerves. A commonly used prescription dose for benign skull base tumors is a total of 54 Gy given with 1.8–2.0 Gy per fraction.
Radiosurgery with the Gamma Knife uses 201 separate cobalt sources, all aimed at a high dose at precisely one fixed target, with one or more isocenters employed, depending on the size and shape of the tumor [1, 2, 3]. A commonly used dose for benign skull base tumors is 12 Gy
Cyberknife is used in some centers and is a frameless robotic radiosurgery system, which is typically delivered in multiple session. It is a relatively safe and effective treatment for skull base tumors [10].
More recently, proton beam therapy has been introduced and is gaining progressively widespread use. It relies on protons produced end emitted by a synchrotron or cyclotron. The protons travel to a specific depth in the body depending on their energy and when striking the tumor rapidly emit their energy. It is well suited and used for various benign skull base tumors. Proton beam therapy is an effective treatment modality, with favorable long-term tumor control rates [11, 12].
The differences between Gamma Knife, LINAC and Cyberknife are summarized in Table 1.
Developed exclusively for brain surgery | Not developed exclusively for brain surgery | Developed primarily for brain surgery but can be used for other regions | |
Millimeter accuracy | Millimeter accuracy | Submillimeter accuracy | |
Gamma rays from Cobalt-60 source | 6-MV X-rays | Compact linac with 6 MeV photons | |
201 fixed concentric non-opposed beams | Non-coplanar arcs
| Robotic arm with 6 degrees of freedom of movement; nonisocentric, where beams can be directed from any desired angle | |
A lightweight stereotactic frame is affixed to the head for rigid stabilization | Thermoplastic face mask, less rigid | Does not need head fixation, thus more flexible | |
Single treatment session | Single or multiple (i.e., 30) treatment sessions | Single or multiple (hypofractionated) up to five treatment sessions |
Differences between gamma knife, LINAC, and cyberknife.
Meningiomas, pituitary adenomas, craniopharyngiomas, and vestibular schwannomas constitute the vast majority of primary skull base tumors suitable for stereotactic radiation therapy or radiosurgery.
Meningiomas are the most common primary intracranial tumors, the prevalence being approximately 100 per 100,000 [13, 14]. They are slow-growing tumors, most often benign and dural-based. Meningiomas are classified according to the World Health Organization (WHO) classification of grade, where grade I is benign, grade II atypical, and grade III anaplastic [13, 15, 16, 17]. Approximately 95% of intracranial meningiomas are benign and approximately 5% are atypical or anaplastic [13, 15]. Atypical and anaplastic meningiomas have an increased recurrence and mortality risk [15, 16]. In addition to WHO grade, prognosis and recurrence risk depend on the radicality of resection [13, 18]. Anterior skull base meningiomas are defined as arising anterior to the chiasmatic sulcus, which separates the middle and the anterior cranial fossa. Anterior skull base meningiomas include olfactory groove, tuberculum sellae, sphenoid wing, cavernous sinus, and optic nerve sheath meningiomas [19, 20]. Medial skull base meningiomas include clival and petroclival meningiomas [21]. Olfactory groove meningiomas arise from the cribriform plate in the midline and often compress or distort the olfactory and optic nerves and optic chiasm (Figure 1). Tuberculum sellae meningiomas are usually located in the suprasellar and subchiasmal region in the midline and often compress the optic nerves and internal carotid arteries (Figure 2). Sphenoid wing meningiomas arise from the sphenoid wing and often involve the optic nerves, the cavernous sinus, or carotid arteries, and cause neurological damage by direct compression of adjacent cranial nerves (Figure 3). Cavernous sinus meningiomas may either originate within the cavernous sinus and spread outside of it or originate outside the cavernous sinus and invade it. Cavernous sinus meningiomas often present with symptoms related to compression of structures within the cavernous sinus, resulting in ophthalmoplegia or facial pain or numbness or ischemic stroke due to compression of the carotid artery and with tumor extending beyond the cavernous sinus, can also affect the optic nerves and chiasm or the pituitary gland (Figure 4). Total resection is often not possible, and resection is also associated with risks to the carotid artery, or damage to the cranial nerves of the cavernous sinus [22]. Optic nerve sheath meningiomas are rare, accounting for 1–2% of intracranial meningiomas, and due to their localization, management is often conservative. Finally, clival and petroclival meningiomas arise from the clivus and typically compress the brain stem, and they often involve the cavernous sinus and are surgically particularly challenging (Figure 5) [21].
MRI scan with gadolinium (Gd) of an olfactory groove meningioma.
MRI scan with Gd of a tuberculum sellae meningioma.
MRI scan with Gd of a large left-sided sphenoid wing meningioma.
Stereotactic radiation therapy dose plan in BrainLab/iPlan, of a right cavernous sinus meningioma, with isodose lines, demonstrating collateral irradiation of the optic chiasm, pituitary gland, and vascular structures of the cavernous sinus and circle of Willis.
MRI scan with Gd of a right petroclival meningioma.
With incompletely resected or recurrent skull base meningiomas, stereotactic radiation therapy or radiosurgery is recommended [13, 23]. Also, the extent of surgical tumor removal is dependent on tumor’s localization adjacent to critical structures. Surgical treatment of cavernous sinus meningiomas, in particular, is associated with a high risk of cranial nerve injury, especially ophthalmoplegia, and therefore a high proportion of cavernous sinus meningiomas are treated by stereotactic radiation or radiosurgery and in some institutions is the first-line treatment. Generally, stereotactic radiosurgery or fractionated radiation therapy is frequently used as primary therapy in surgically high-risk tumors, resulting in good local control [4, 10, 13, 23, 24].
Pituitary adenomas are one of the most common intracranial tumors and are associated with a high rate of morbidity and mortality [25]. The prevalence of pituitary adenomas is approximately 100 per 100.000 [26, 27, 28]. Radical tumor resection is indicated, with a transsphenoidal approach [29]. Adenomas that secrete hormones are called functioning adenomas, and adenomas that do not secrete hormones are called nonfunctioning adenomas [28]. Nonfunctioning and prolactin-secreting adenomas are the most common types of pituitary adenomas, followed by growth hormone secreting and corticotroph adenomas, thyrotropin, and gonadotropin secretin) g adenomas [26, 28, 29]. Macroadenomas, which are defined as tumors with a diameter > 10 mm, are more common than microadenomas, which are <10 mm in diameter [28, 29]. The first-line treatment of prolactinomas is medical, with a dopamine agonist (Figure 6) [28].
MRI sagittal T1 with Gd of a pituitary microadenoma.
Nonfunctioning pituitary adenomas are often large at presentation and are usually diagnosed due to their mass effect, visual loss, and hypopituitarism [27, 28]. Occasionally, they may constitute an asymptomatic incidental finding. They may also cause hyperprolactinemia due to pressure on the pituitary stalk. The main indication for surgery is reversal of visual loss, and in many cases, it may reverse hypopituitarism [29]. When surgical treatment does not provide sufficient disease control or has serious side effects, such as visual loss, then stereotactic radiosurgery or fractionated stereotactic radiation therapy is indicated, and in some instances, this may then be the sole treatment of the tumor (Figure 7). Also, stereotactic irradiation may be effective when surgery has failed to restore biochemical control in hormone-secreting adenomas [7].
FSRT dose plan of a large pituitary macroadenoma.
Craniopharyngiomas are usually benign epithelial tumors originating from remnants of the Rathke’s pouch, localized in the sellar or suprasellar region [30]. They are rare, with an incidence of 0.5–2 per 100,000 a year [31, 32]. They often present during childhood or adolescence and persist into adulthood [32]. They are cystic or solid or mixed cystic and solid and frequently contain calcifications (Figure 8) [31]. Presenting symptoms include visual field defects, pituitary hormone deficiency, and diabetes insipidus [30, 31, 32]. Craniopharyngiomas can be very challenging in terms of surgical management and can cause significant morbidity, despite their benign nature [33]. There are two distinct histological types of craniopharyngiomas. The adamantinomatous type is predominant in children, is more cystic and calcified and large, and often adherent to the brain. The less common papillary type almost exclusively presents in adults, is less infiltrative, and may be more amenable to surgery [34]. However, papillary craniopharyngiomas are well suited for stereotactic radiosurgery or fractionated stereotactic radiation therapy, as they are more radiosensitive and rarely recur after irradiation. Due to the high recurrence rate after subtotal resection, adjuvant irradiation is often warranted, with stereotactic radiosurgery or fractionated stereotactic radiation therapy [30, 35]. The main indication for stereotactic radiation therapy or stereotactic radiosurgery for craniopharyngiomas is thus when surgical control is not possible, or in case of tumor recurrence where the risks of surgery outweigh the benefits [36, 37].
MRI scan sagittal with Gd demonstrating a mainly solid craniopharyngioma in a 16-year-old adolescent.
Vestibular schwannomas are slow-growing and benign tumors originating from the Schwann cell sheath of the cochleovestibular nerve (Figure 9) [38, 39]. The incidence is 1–2 in 100.000 a year [38, 39]. As the vestibular schwannomas grow, they affect hearing and balance, with unilateral hearing loss, tinnitus, and balance disturbances [39, 40]. With increasing tumor growth, the facial nerve can also be affected. Bilateral vestibular schwannomas with bilateral hearing loss are usually associated with neurofibromatosis type 2. Surgery is the standard treatment of vestibular schwannomas, including microsurgery and hearing preservation surgery [38]. More recently, stereotactic radiosurgery and radiation therapy have been introduced for the treatment of vestibular schwannomas with the aim of tumor control and hearing preservation, and controlled studies have found the results to be superior to microsurgery for small tumors less than 3 cm [38, 39, 40]. Sometimes a conservative wait and scan approach is appropriate, reserving treatment in case of tumor growth or neurological deterioration.
MRI scan with Gd demonstrating a small left-sided vestibular schwannoma.
For skull base meningiomas, nonfunctioning pituitary adenomas, craniopharyngiomas, and vestibular schwannomas, the major goal of treatment is tumor control. Tumor control is defined as stable or reduced size of tumor after treatment. Long-term tumor control after fractionated stereotactic radiation therapy of benign anterior skull base tumors is well established from several large series and in several cases is superior to surgery, with long-term tumor control rates reported in the range of 88–100% for skull base meningiomas [4, 24, 41, 42, 43, 44, 45, 46], 92–99% for pituitary adenomas [47, 48, 49, 50, 51, 52, 53], 75–100% for craniopharyngiomas [34, 37, 54, 55], and 85–100% for vestibular schwannomas [38, 40]. Long-term tumor control rates after stereotactic radiosurgery with LINAC or Gamma Knife have been reported to be similar [2, 4, 6, 8, 9, 36, 38, 56]. For hormone-secreting pituitary adenomas, an equally important goal of treatment is biochemical control [56]. For nonfunctioning pituitary adenomas, biochemical control rates of 50% of hormone-producing adenomas have been reported [7].
Tumor control can be evaluated on a contrast-enhanced MRI scan compared with the MRI scan before the radiation therapy. Pre- and post-therapy MRI and CT scans of the treatment plans are fused, with the gross tumor volume as reference [57]. Tumor volume is then calculated using 3D volumetric assessment with treatment planning software, i.e., from Electa, BrainLab, or Varian Eclipse. Tumor control is defined as stable size or regression of the tumor. A change in tumor volume by ≥25% can be considered a change in size, and a change in tumor volume < 25% can be considered stable size [34].
Serial neuroimaging follow-up until at least 10 years after treatment is generally recommended.
During the irradiation of tumors, with close anatomical relation to the optic chiasm and nerves, a certain degree of collateral irradiation of these intact but sensitive structures occurs [58, 59]. In therapy protocols, the optic nerves, chiasm, and tracts are usually outlined and defined as organs at risk (OAR) [57]. Radiation-induced optic neuropathy (RION) is defined as painless rapid visual loss and is attributed to radiation necrosis of the anterior optic pathways [60]. It often has a delayed onset and can result in either visual acuity or visual field loss. The risk of radiation-induced optic neuropathy is dependent on both the total cumulated radiation dose and the fraction dose [60]. The risk is markedly increased at cumulated optic chiasm radiation doses of ≥60 Gy in the case of fractionated stereotactic radiation therapy and at a single dose of >12 Gy in the case of radiosurgery [60]. The risk is greater with increasing age, preexisting compression of the optic nerves/chiasm, and previous radiation therapy. Percentages of 3–7 and 7–20% of RION in the dose ranges 55–60 and above 60 Gy, respectively, have been reported, as presented in the review by the QUANTEC initiative [60].
Fractionated stereotactic radiation therapy combines the advantage of a high accuracy of stereotactic technique and the biological advantage of fractionation [1, 48]. For stereotactic radiosurgery (SRS) of tumors in the vicinity of the optic structures, there is a dose-limiting factor, meaning that the minimal effective tumor dose may be equal to or greater than the dose tolerated by the optic structures. For example, the treatment of tumors of the cavernous sinus, with single-dose SRS, has been shown not to affect the optic pathways at a single dose of <10, whereas the incidence of optic neuropathy has been shown to be 27% after a single dose of 10 Gy–15 Gy and 78% after a single dose of >15 Gy [58]. Other SRS studies of perioptic tumors have reported variable results [4, 5, 6, 61, 62, 63, 64].
The pituitary gland is particularly sensitive to radiation, and hypopituitarism is the most common side effect after radiation therapy [65]. When high-dose radiation is applied directly to the pituitary gland for the treatment of pituitary adenomas, frequently it results in pituitary deficiency of one or more hormonal axes, and this correlates well with radiation dose to the pituitary gland [65, 66]. Furthermore, radiation damage of the hypothalamus can result in hypopituitarism [50]. Treatment requiring hypopituitarism of one or more hormonal axes has been reported in around 8% of these patients [7].
Occlusion of the carotid artery or its branches leading to cerebral infarction or ischemic stroke is a potentially serious and life-threatening complication after stereotactic radiation therapy involving the extra- or intracavernous portion of the carotid artery or the Circle of Willis [67]. Although considered to be relatively rare, radiation-induced cerebral infarction has been reported after single fraction stereotactic radiosurgery or radiation therapy of meningiomas, pituitary adenomas, craniopharyngiomas, and vestibular schwannomas, with an occurrence of 1–7% [24, 46, 68, 69, 70]. However, the risk of cerebral infarction may not be increased when compared with the incidence in the general population. Predisposing risk factors identified for ischemic events are smoking, hypertension, and hyperlipidemia, as well as increased age [70]. Cerebral infarction is by definition a clinical diagnosis; therefore, subclinical infarctions only detectable by neuroimaging may occur [70].
Both stereotactic radiosurgery and fractionated stereotactic radiation therapy have been shown to accelerate the naturally occurring hearing loss in patients in around 50% of treated patients with vestibular schwannoma, and the degree of hearing loss is correlated to the radiation dose to the cochlea [38, 40].
The occurrence of intracranial malignancies after conventional radiation therapy is well known but is not well established following stereotactic radiation therapy and radiosurgery, but since this is often a late event, existing studies may not have had long enough follow-up. It would be feasible to conduct such a study, but with very long-term (10–20 years) follow-up.
Benign anterior skull base tumors include meningiomas, pituitary adenomas, craniopharyngiomas, and vestibular schwannomas. As an adjuvant therapy to surgery or when surgical treatment carries too high a risk of complications, a highly precise focused radiation, known as fractionated stereotactic radiation therapy (FSRT) or stereotactic radiosurgery (SRS) can be delivered to the tumor. Treatment modalities include Gamma Knife for SRS, LINAC for FSRT/SRS, Cyberknife for SRS or hypo fractionated FSRT, and more recently, proton beam therapy. FSRT in particular combines the high accuracy of stereotactic radiosurgery and the benefit of fractionation. Existing studies include systematic analysis of complications and risk factors FSRT/SRS of tumors with localizations relating to vision, hormone-secreting regions, cerebral vasculature, and hearing. Paying attention to risk reduction is extremely important to prevent complications. Existing studies provide evidence of good long-term tumor control for benign tumors of the skull base. Upweighting the risks against surgical complications and uncontrolled tumor growth, stereotactic radiotherapy and radiosurgery appear to be relatively safe as a treatment of patients with benign anterior skull base tumors. However, improved dose planning techniques may be able to reduce the incidence of side effects further. Further studies with very long-time follow-up including the potential for malignancy are needed.
The author declares no conflict of interest.
Special thanks to Tina Obbekjaer, Mahmoud Albarazi, and Marianne Juhler, for their advice during the preparation of this book chapter.
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Luna-Muñoz and M.A.\nMeraz-Ríos",authors:[{id:"42225",title:"Dr.",name:"Jose",middleName:null,surname:"Luna-Muñoz",slug:"jose-luna-munoz",fullName:"Jose Luna-Muñoz"},{id:"114746",title:"Dr.",name:"Marco",middleName:null,surname:"Meraz-Ríos",slug:"marco-meraz-rios",fullName:"Marco Meraz-Ríos"},{id:"169616",title:"Dr.",name:"Maria del Carmen",middleName:null,surname:"Cardenas-Aguayo",slug:"maria-del-carmen-cardenas-aguayo",fullName:"Maria del Carmen Cardenas-Aguayo"},{id:"169857",title:"Dr.",name:"Maria del Carmen",middleName:null,surname:"Silva-Lucero",slug:"maria-del-carmen-silva-lucero",fullName:"Maria del Carmen Silva-Lucero"},{id:"169858",title:"Dr.",name:"Maribel",middleName:null,surname:"Cortes-Ortiz",slug:"maribel-cortes-ortiz",fullName:"Maribel Cortes-Ortiz"},{id:"169859",title:"Dr.",name:"Berenice",middleName:null,surname:"Jimenez-Ramos",slug:"berenice-jimenez-ramos",fullName:"Berenice Jimenez-Ramos"},{id:"169860",title:"Dr.",name:"Laura",middleName:null,surname:"Gomez-Virgilio",slug:"laura-gomez-virgilio",fullName:"Laura Gomez-Virgilio"},{id:"169861",title:"Dr.",name:"Gerardo",middleName:null,surname:"Ramirez-Rodriguez",slug:"gerardo-ramirez-rodriguez",fullName:"Gerardo Ramirez-Rodriguez"},{id:"169862",title:"Dr.",name:"Eduardo",middleName:null,surname:"Vera-Arroyo",slug:"eduardo-vera-arroyo",fullName:"Eduardo Vera-Arroyo"},{id:"169863",title:"Dr.",name:"Rosana Sofia",middleName:null,surname:"Fiorentino-Perez",slug:"rosana-sofia-fiorentino-perez",fullName:"Rosana Sofia Fiorentino-Perez"},{id:"169864",title:"Dr.",name:"Ubaldo",middleName:null,surname:"Garcia",slug:"ubaldo-garcia",fullName:"Ubaldo Garcia"}]},{id:"58070",doi:"10.5772/intechopen.72427",title:"MRI Medical Image Denoising by Fundamental Filters",slug:"mri-medical-image-denoising-by-fundamental-filters",totalDownloads:2564,totalCrossrefCites:17,totalDimensionsCites:30,abstract:"Nowadays Medical imaging technique Magnetic Resonance Imaging (MRI) plays an important role in medical setting to form high standard images contained in the human brain. MRI is commonly used once treating brain, prostate cancers, ankle and foot. The Magnetic Resonance Imaging (MRI) images are usually liable to suffer from noises such as Gaussian noise, salt and pepper noise and speckle noise. So getting of brain image with accuracy is very extremely task. An accurate brain image is very necessary for further diagnosis process. During this chapter, a median filter algorithm will be modified. Gaussian noise and Salt and pepper noise will be added to MRI image. A proposed Median filter (MF), Adaptive Median filter (AMF) and Adaptive Wiener filter (AWF) will be implemented. The filters will be used to remove the additive noises present in the MRI images. The noise density will be added gradually to MRI image to compare performance of the filters evaluation. The performance of these filters will be compared exploitation the applied mathematics parameter Peak Signal-to-Noise Ratio (PSNR).",book:{id:"6144",slug:"high-resolution-neuroimaging-basic-physical-principles-and-clinical-applications",title:"High-Resolution Neuroimaging",fullTitle:"High-Resolution Neuroimaging - Basic Physical Principles and Clinical Applications"},signatures:"Hanafy M. Ali",authors:[{id:"213318",title:"Dr.",name:"Hanafy",middleName:"M.",surname:"Ali",slug:"hanafy-ali",fullName:"Hanafy Ali"}]},{id:"41589",doi:"10.5772/50323",title:"The Role of the Amygdala in Anxiety Disorders",slug:"the-role-of-the-amygdala-in-anxiety-disorders",totalDownloads:9671,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"2599",slug:"the-amygdala-a-discrete-multitasking-manager",title:"The Amygdala",fullTitle:"The Amygdala - A Discrete Multitasking Manager"},signatures:"Gina L. Forster, Andrew M. Novick, Jamie L. Scholl and Michael J. Watt",authors:[{id:"145620",title:"Dr.",name:"Gina",middleName:null,surname:"Forster",slug:"gina-forster",fullName:"Gina Forster"},{id:"146553",title:"BSc.",name:"Andrew",middleName:null,surname:"Novick",slug:"andrew-novick",fullName:"Andrew Novick"},{id:"146554",title:"MSc.",name:"Jamie",middleName:null,surname:"Scholl",slug:"jamie-scholl",fullName:"Jamie Scholl"},{id:"146555",title:"Dr.",name:"Michael",middleName:null,surname:"Watt",slug:"michael-watt",fullName:"Michael Watt"}]},{id:"26258",doi:"10.5772/28300",title:"Excitotoxicity and Oxidative Stress in Acute Ischemic Stroke",slug:"excitotoxicity-and-oxidative-stress-in-acute-ischemic-stroke",totalDownloads:7157,totalCrossrefCites:6,totalDimensionsCites:25,abstract:null,book:{id:"931",slug:"acute-ischemic-stroke",title:"Acute Ischemic Stroke",fullTitle:"Acute Ischemic Stroke"},signatures:"Ramón Rama Bretón and Julio César García Rodríguez",authors:[{id:"73430",title:"Prof.",name:"Ramon",middleName:null,surname:"Rama",slug:"ramon-rama",fullName:"Ramon Rama"},{id:"124643",title:"Prof.",name:"Julio Cesar",middleName:null,surname:"García",slug:"julio-cesar-garcia",fullName:"Julio Cesar García"}]},{id:"62072",doi:"10.5772/intechopen.78695",title:"Brain-Computer Interface and Motor Imagery Training: The Role of Visual Feedback and Embodiment",slug:"brain-computer-interface-and-motor-imagery-training-the-role-of-visual-feedback-and-embodiment",totalDownloads:1439,totalCrossrefCites:13,totalDimensionsCites:23,abstract:"Controlling a brain-computer interface (BCI) is a difficult task that requires extensive training. Particularly in the case of motor imagery BCIs, users may need several training sessions before they learn how to generate desired brain activity and reach an acceptable performance. A typical training protocol for such BCIs includes execution of a motor imagery task by the user, followed by presentation of an extending bar or a moving object on a computer screen. In this chapter, we discuss the importance of a visual feedback that resembles human actions, the effect of human factors such as confidence and motivation, and the role of embodiment in the learning process of a motor imagery task. Our results from a series of experiments in which users BCI-operated a humanlike android robot confirm that realistic visual feedback can induce a sense of embodiment, which promotes a significant learning of the motor imagery task in a short amount of time. We review the impact of humanlike visual feedback in optimized modulation of brain activity by the BCI users.",book:{id:"6610",slug:"evolving-bci-therapy-engaging-brain-state-dynamics",title:"Evolving BCI Therapy",fullTitle:"Evolving BCI Therapy - Engaging Brain State Dynamics"},signatures:"Maryam Alimardani, Shuichi Nishio and Hiroshi Ishiguro",authors:[{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro"},{id:"231131",title:"Dr.",name:"Maryam",middleName:null,surname:"Alimardani",slug:"maryam-alimardani",fullName:"Maryam Alimardani"},{id:"231134",title:"Dr.",name:"Shuichi",middleName:null,surname:"Nishio",slug:"shuichi-nishio",fullName:"Shuichi Nishio"}]}],mostDownloadedChaptersLast30Days:[{id:"29764",title:"Underlying Causes of Paresthesia",slug:"underlying-causes-of-paresthesia",totalDownloads:192666,totalCrossrefCites:3,totalDimensionsCites:7,abstract:null,book:{id:"1069",slug:"paresthesia",title:"Paresthesia",fullTitle:"Paresthesia"},signatures:"Mahdi Sharif-Alhoseini, Vafa Rahimi-Movaghar and Alexander R. Vaccaro",authors:[{id:"91165",title:"Prof.",name:"Vafa",middleName:null,surname:"Rahimi-Movaghar",slug:"vafa-rahimi-movaghar",fullName:"Vafa Rahimi-Movaghar"}]},{id:"63258",title:"Anatomy and Function of the Hypothalamus",slug:"anatomy-and-function-of-the-hypothalamus",totalDownloads:4558,totalCrossrefCites:6,totalDimensionsCites:12,abstract:"The hypothalamus is a small but important area of the brain formed by various nucleus and nervous fibers. Through its neuronal connections, it is involved in many complex functions of the organism such as vegetative system control, homeostasis of the organism, thermoregulation, and also in adjusting the emotional behavior. The hypothalamus is involved in different daily activities like eating or drinking, in the control of the body’s temperature and energy maintenance, and in the process of memorizing. It also modulates the endocrine system through its connections with the pituitary gland. Precise anatomical description along with a correct characterization of the component structures is essential for understanding its functions.",book:{id:"6331",slug:"hypothalamus-in-health-and-diseases",title:"Hypothalamus in Health and Diseases",fullTitle:"Hypothalamus in Health and Diseases"},signatures:"Miana Gabriela Pop, Carmen Crivii and Iulian Opincariu",authors:null},{id:"57103",title:"GABA and Glutamate: Their Transmitter Role in the CNS and Pancreatic Islets",slug:"gaba-and-glutamate-their-transmitter-role-in-the-cns-and-pancreatic-islets",totalDownloads:3478,totalCrossrefCites:3,totalDimensionsCites:9,abstract:"Glutamate and gamma-aminobutyric acid (GABA) are the major neurotransmitters in the mammalian brain. Inhibitory GABA and excitatory glutamate work together to control many processes, including the brain’s overall level of excitation. The contributions of GABA and glutamate in extra-neuronal signaling are by far less widely recognized. In this chapter, we first discuss the role of both neurotransmitters during development, emphasizing the importance of the shift from excitatory to inhibitory GABAergic neurotransmission. The second part summarizes the biosynthesis and role of GABA and glutamate in neurotransmission in the mature brain, and major neurological disorders associated with glutamate and GABA receptors and GABA release mechanisms. The final part focuses on extra-neuronal glutamatergic and GABAergic signaling in pancreatic islets of Langerhans, and possible associations with type 1 diabetes mellitus.",book:{id:"6237",slug:"gaba-and-glutamate-new-developments-in-neurotransmission-research",title:"GABA And Glutamate",fullTitle:"GABA And Glutamate - New Developments In Neurotransmission Research"},signatures:"Christiane S. Hampe, Hiroshi Mitoma and Mario Manto",authors:[{id:"210220",title:"Prof.",name:"Christiane",middleName:null,surname:"Hampe",slug:"christiane-hampe",fullName:"Christiane Hampe"},{id:"210485",title:"Prof.",name:"Mario",middleName:null,surname:"Manto",slug:"mario-manto",fullName:"Mario Manto"},{id:"210486",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Mitoma",slug:"hiroshi-mitoma",fullName:"Hiroshi Mitoma"}]},{id:"35802",title:"Cross-Cultural/Linguistic Differences in the Prevalence of Developmental Dyslexia and the Hypothesis of Granularity and Transparency",slug:"cross-cultural-linguistic-differences-in-the-prevalence-of-developmental-dyslexia-and-the-hypothesis",totalDownloads:3601,totalCrossrefCites:2,totalDimensionsCites:7,abstract:null,book:{id:"673",slug:"dyslexia-a-comprehensive-and-international-approach",title:"Dyslexia",fullTitle:"Dyslexia - A Comprehensive and International Approach"},signatures:"Taeko N. Wydell",authors:[{id:"87489",title:"Prof.",name:"Taeko",middleName:"N.",surname:"Wydell",slug:"taeko-wydell",fullName:"Taeko Wydell"}]},{id:"58597",title:"Testosterone and Erectile Function: A Review of Evidence from Basic Research",slug:"testosterone-and-erectile-function-a-review-of-evidence-from-basic-research",totalDownloads:1331,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Androgens are essential for male physical activity and normal erectile function. Hence, age-related testosterone deficiency, known as late-onset hypogonadism (LOH), is considered a risk factor for erectile dysfunction (ED). This chapter summarizes relevant basic research reports examining the effects of testosterone on erectile function. Testosterone affects several organs and is especially active on the erectile tissue. The mechanism of testosterone deficiency effects on erectile function and the results of testosterone replacement therapy (TRT) have been well studied. Testosterone affects nitric oxide (NO) production and phosphodiesterase type 5 (PDE-5) expression in the corpus cavernosum through molecular pathways, preserves smooth muscle contractility by regulating both contraction and relaxation, and maintains the structure of the corpus cavernosum. Interestingly, testosterone deficiency has relationship to neurological diseases, which leads to ED. Testosterone replacement therapy is widely used to treat patients with testosterone deficiency; however, this treatment might also induce some problems. Basic research suggests that PDE-5 inhibitors, L-citrulline, and/or resveratrol therapy might be effective therapeutic options for testosterone deficiency-induced ED. Future research should confirm these findings through more specific experiments using molecular tools and may shed more light on endocrine-related ED and its possible treatments.",book:{id:"5994",slug:"sex-hormones-in-neurodegenerative-processes-and-diseases",title:"Sex Hormones in Neurodegenerative Processes and Diseases",fullTitle:"Sex Hormones in Neurodegenerative Processes and Diseases"},signatures:"Tomoya Kataoka and Kazunori Kimura",authors:[{id:"219042",title:"Ph.D.",name:"Tomoya",middleName:null,surname:"Kataoka",slug:"tomoya-kataoka",fullName:"Tomoya Kataoka"},{id:"229066",title:"Prof.",name:"Kazunori",middleName:null,surname:"Kimura",slug:"kazunori-kimura",fullName:"Kazunori Kimura"}]}],onlineFirstChaptersFilter:{topicId:"18",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81646",title:"Cortical Plasticity under Ketamine: From Synapse to Map",slug:"cortical-plasticity-under-ketamine-from-synapse-to-map",totalDownloads:15,totalDimensionsCites:0,doi:"10.5772/intechopen.104787",abstract:"Sensory systems need to process signals in a highly dynamic way to efficiently respond to variations in the animal’s environment. For instance, several studies showed that the visual system is subject to neuroplasticity since the neurons’ firing changes according to stimulus properties. This dynamic information processing might be supported by a network reorganization. Since antidepressants influence neurotransmission, they can be used to explore synaptic plasticity sustaining cortical map reorganization. To this goal, we investigated in the primary visual cortex (V1 of mouse and cat), the impact of ketamine on neuroplasticity through changes in neuronal orientation selectivity and the functional connectivity between V1 cells, using cross correlation analyses. We found that ketamine affects cortical orientation selectivity and alters the functional connectivity within an assembly. These data clearly highlight the role of the antidepressant drugs in inducing or modeling short-term plasticity in V1 which suggests that cortical processing is optimized and adapted to the properties of the stimulus.",book:{id:"11374",title:"Sensory Nervous System - Computational Neuroimaging Investigations of Topographical Organization in Human Sensory Cortex",coverURL:"https://cdn.intechopen.com/books/images_new/11374.jpg"},signatures:"Ouelhazi Afef, Rudy Lussiez and Molotchnikoff Stephane"},{id:"81582",title:"The Role of Cognitive Reserve in Executive Functioning and Its Relationship to Cognitive Decline and Dementia",slug:"the-role-of-cognitive-reserve-in-executive-functioning-and-its-relationship-to-cognitive-decline-and",totalDownloads:23,totalDimensionsCites:0,doi:"10.5772/intechopen.104646",abstract:"In this chapter, we explore how cognitive reserve is implicated in coping with the negative consequences of brain pathology and age-related cognitive decline. Individual differences in cognitive performance are based on different brain mechanisms (neural reserve and neural compensation), and reflect, among others, the effect of education, occupational attainment, leisure activities, and social involvement. These cognitive reserve proxies have been extensively associated with efficient executive functioning. We discuss and focus particularly on the compensation mechanisms related to the frontal lobe and its protective role, in maintaining cognitive performance in old age or even mitigating the clinical expression of dementia.",book:{id:"11742",title:"Neurophysiology",coverURL:"https://cdn.intechopen.com/books/images_new/11742.jpg"},signatures:"Gabriela Álvares-Pereira, Carolina Maruta and Maria Vânia Silva-Nunes"},{id:"81488",title:"Aggression and Sexual Behavior: Overlapping or Distinct Roles of 5-HT1A and 5-HT1B Receptors",slug:"aggression-and-sexual-behavior-overlapping-or-distinct-roles-of-5-ht1a-and-5-ht1b-receptors",totalDownloads:20,totalDimensionsCites:0,doi:"10.5772/intechopen.104872",abstract:"Distinct brain mechanisms for male aggressive and sexual behavior are present in mammalian species, including man. However, recent evidence suggests a strong connection and even overlap in the central nervous system (CNS) circuitry involved in aggressive and sexual behavior. The serotonergic system in the CNS is strongly involved in male aggressive and sexual behavior. In particular, 5-HT1A and 5-HT1B receptors seem to play a critical role in the modulation of these behaviors. The present chapter focuses on the effects of 5-HT1A- and 5-HT1B-receptor ligands in male rodent aggression and sexual behavior. Results indicate that 5-HT1B-heteroreceptors play a critical role in the modulation of male offensive behavior, although a definite role of 5-HT1A-auto- or heteroreceptors cannot be ruled out. 5-HT1A receptors are clearly involved in male sexual behavior, although it has to be yet unraveled whether 5-HT1A-auto- or heteroreceptors are important. Although several key nodes in the complex circuitry of aggression and sexual behavior are known, in particular in the medial hypothalamus, a clear link or connection to these critical structures and the serotonergic key receptors is yet to be determined. This information is urgently needed to detect and develop new selective anti-aggressive (serenic) and pro-sexual drugs for human applications.",book:{id:"10195",title:"Serotonin and the CNS - New Developments in Pharmacology and Therapeutics",coverURL:"https://cdn.intechopen.com/books/images_new/10195.jpg"},signatures:"Berend Olivier and Jocelien D.A. Olivier"},{id:"81093",title:"Prehospital and Emergency Room Airway Management in Traumatic Brain Injury",slug:"prehospital-and-emergency-room-airway-management-in-traumatic-brain-injury",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.104173",abstract:"Airway management in trauma is critical and may impact patient outcomes. Particularly in traumatic brain injury (TBI), depressed level of consciousness may be associated with compromised protective airway reflexes or apnea, which can increase the risk of aspiration or result in hypoxemia and worsen the secondary brain damage. Therefore, patients with TBI and Glasgow Coma Scale (GCS) ≤ 8 have been traditionally managed by prehospital or emergency room (ER) endotracheal intubation. However, recent evidence challenged this practice and even suggested that routine intubation may be harmful. This chapter will address the indications and optimal method of securing the airway, prehospital and in the ER, in patients with traumatic brain injury.",book:{id:"11367",title:"Traumatic Brain Injury",coverURL:"https://cdn.intechopen.com/books/images_new/11367.jpg"},signatures:"Dominik A. Jakob, Jean-Cyrille Pitteloud and Demetrios Demetriades"},{id:"81011",title:"Amino Acids as Neurotransmitters. The Balance between Excitation and Inhibition as a Background for Future Clinical Applications",slug:"amino-acids-as-neurotransmitters-the-balance-between-excitation-and-inhibition-as-a-background-for-f",totalDownloads:19,totalDimensionsCites:0,doi:"10.5772/intechopen.103760",abstract:"For more than 30 years, amino acids have been well-known (and essential) participants in neurotransmission. They act as both neuromediators and metabolites in nervous tissue. Glycine and glutamic acid (glutamate) are prominent examples. These amino acids are agonists of inhibitory and excitatory membrane receptors, respectively. Moreover, they play essential roles in metabolic pathways and energy transformation in neurons and astrocytes. Despite their obvious effects on the brain, their potential role in therapeutic methods remains uncertain in clinical practice. In the current chapter, a comparison of the crosstalk between these two systems, which are responsible for excitation and inhibition in neurons, is presented. The interactions are discussed at the metabolic, receptor, and transport levels. Reaction-diffusion and a convectional flow into the interstitial fluid create a balanced distribution of glycine and glutamate. Indeed, the neurons’ final physiological state is a result of a balance between the excitatory and inhibitory influences. However, changes to the glycine and/or glutamate pools under pathological conditions can alter the state of nervous tissue. Thus, new therapies for various diseases may be developed on the basis of amino acid medication.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Yaroslav R. Nartsissov"},{id:"80821",title:"Neuroimmunology and Neurological Manifestations of COVID-19",slug:"neuroimmunology-and-neurological-manifestations-of-covid-19",totalDownloads:41,totalDimensionsCites:0,doi:"10.5772/intechopen.103026",abstract:"Infection with SARS-CoV-2 is causing coronavirus disease in 2019 (COVID-19). Besides respiratory symptoms due to an attack on the broncho-alveolar system, COVID-19, among others, can be accompanied by neurological symptoms because of the affection of the nervous system. These can be caused by intrusion by SARS-CoV-2 of the central nervous system (CNS) and peripheral nervous system (PNS) and direct infection of local cells. In addition, neurological deterioration mediated by molecular mimicry to virus antigens or bystander activation in the context of immunological anti-virus defense can lead to tissue damage in the CNS and PNS. In addition, cytokine storm caused by SARS-CoV-2 infection in COVID-19 can lead to nervous system related symptoms. Endotheliitis of CNS vessels can lead to vessel occlusion and stroke. COVID-19 can also result in cerebral hemorrhage and sinus thrombosis possibly related to changes in clotting behavior. Vaccination is most important to prevent COVID-19 in the nervous system. There are symptomatic or/and curative therapeutic approaches to combat COVID-19 related nervous system damage that are partly still under study.",book:{id:"10890",title:"Recent Advances in Neurochemistry",coverURL:"https://cdn.intechopen.com/books/images_new/10890.jpg"},signatures:"Robert Weissert"}],onlineFirstChaptersTotal:17},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[],lsSeriesList:[],hsSeriesList:[],sshSeriesList:[],testimonialsList:[]},series:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems.
\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems.
\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.
\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
",annualVolume:11966,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/38.jpg",editor:{id:"110740",title:"Dr.",name:"Ismail M.M.",middleName:null,surname:"Rahman",fullName:"Ismail M.M. Rahman",profilePictureURL:"https://mts.intechopen.com/storage/users/110740/images/2319_n.jpg",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorThree:null,editorialBoard:[{id:"252368",title:"Dr.",name:"Meng-Chuan",middleName:null,surname:"Ong",fullName:"Meng-Chuan Ong",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRVotQAG/Profile_Picture_2022-05-20T12:04:28.jpg",institutionString:null,institution:{name:"Universiti Malaysia Terengganu",institutionURL:null,country:{name:"Malaysia"}}},{id:"63465",title:"Prof.",name:"Mohamed Nageeb",middleName:null,surname:"Rashed",fullName:"Mohamed Nageeb Rashed",profilePictureURL:"https://mts.intechopen.com/storage/users/63465/images/system/63465.gif",institutionString:null,institution:{name:"Aswan University",institutionURL:null,country:{name:"Egypt"}}},{id:"187907",title:"Dr.",name:"Olga",middleName:null,surname:"Anne",fullName:"Olga Anne",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBE5QAO/Profile_Picture_2022-04-07T09:42:13.png",institutionString:null,institution:{name:"Klaipeda State University of Applied Sciences",institutionURL:null,country:{name:"Lithuania"}}}]},{id:"39",title:"Environmental Resilience and Management",keywords:"Anthropic effects, Overexploitation, Biodiversity loss, Degradation, Inadequate Management, SDGs adequate practices",scope:"\r\n\tThe environment is subject to severe anthropic effects. Among them are those associated with pollution, resource extraction and overexploitation, loss of biodiversity, soil degradation, disorderly land occupation and planning, and many others. These anthropic effects could potentially be caused by any inadequate management of the environment. However, ecosystems have a resilience that makes them react to disturbances which mitigate the negative effects. It is critical to understand how ecosystems, natural and anthropized, including urban environments, respond to actions that have a negative influence and how they are managed. It is also important to establish when the limits marked by the resilience and the breaking point are achieved and when no return is possible. The main focus for the chapters is to cover the subjects such as understanding how the environment resilience works, the mechanisms involved, and how to manage them in order to improve our interactions with the environment and promote the use of adequate management practices such as those outlined in the United Nations’ Sustainable Development Goals.
",annualVolume:11967,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},{id:"40",title:"Ecosystems and Biodiversity",keywords:"Ecosystems, Biodiversity, Fauna, Taxonomy, Invasive species, Destruction of habitats, Overexploitation of natural resources, Pollution, Global warming, Conservation of natural spaces, Bioremediation",scope:"