Dr. Papageorgiou obtained a BA in Psychology and Sociology (University of Georgia), a M.H.Sc. in Psychiatric Epidemiology (Johns Hopkins University), and a Ph.D. in the Biological Sciences with a focus on the neuroimaging of morphine (University of Texas - M.D. Anderson Cancer Center; MDACC). She continued with three postdoctoral fellowships: (i) neuroimaging of pain (MDACC); (ii) real-time fMRI neurofeedback of speech impairment (Baylor College of Medicine); and (ii) real-time fMRI neurofeedback of cortical blindness (BCM). As an Assistant Professor of Neurology her research focuses on cortical plasticity, and neuro-rehabilitation of cortical blindness, speech impairment and, chronic pain syndromes, as a result of neurological disorders, traumatic brain injury or, cancer-related symptoms using targeted/individualized real-time fMRI neurofeedback methods. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ The areas of focus of my laboratory - Investigational Targeted Brain Neuro-therapeutics - funded by the McNair Medical Institute, include the neuro-rehabilitation of: visual cortical blindness; speech/motor impairment; and chronic pain as a result of traumatic brain injury, stroke, brain tumor, neurodegenerative disease, and pain syndromes. We use a novel intervention to provide cortically targeted neuro-rehabilitation, called real-time functional MRI neurofeedback to induce reorganization in cortical and subcortical pathways. Patients undergo rneurofeedback in real time to upregulate or downregulate the activity of intact cortical and/or subcortical areas in conjunction with the continuous presentation of visual stimuli inside the MRI environment with the goal to restore or reorganize lesioned pathways associated with vision, speech, or pain. The modulation in the Blood-Oxygen-Level-Dependent (BOLD) signal intensity is achieved by feeding\" back to the patient the magnitude of mean BOLD signal intensity of his/her intact cortical area during the presentation of a stimulus in real-time. The hypothesis is that such training engages Hebbian mechanisms that modulate the activity of intact cortical areas with the goal to improve performance. The current research goals of my laboratory are: To examine and understand the neural mechanisms of brain plasticity in the design of treatments that will enhance nervous system recovery after a brain insult; To achieve long-term effects of personalized neurofeedback interventions at targeted cortical and subcortical areas, and; To optimize rt-fMRI neurofeedback as \"a next generation\" neurotherapeutic approach with the end goal to use this tool in the clinical setting, the effects of which can be translated outside the MRI environment. The long-term goal is to correlate neuroimaging with genetic biomarkers to better understand the pathways and mechanisms involved in the dynamic variability in disease risk and brain reorganization, which will allow us to induce fast, robust and long-term brain neuro-rehabilitation. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Introduction to Advanced Topics in Brain Neuroimaging: Methods and Applications in Health and Disease \'New directions in science are launched by new tools much more often than by new concepts. The effect of a concept-driven revolution is to explain old things in new ways. The effect of a tool-driven revolution is to discover new things that have to be explained.’ -- Freeman Dyson, \"Imagined Worlds\", Harvard University Press, 1997. The purpose of this book is to compile a sample of recent developments in brain functional magnetic resonance imaging (fMRI). In the last two decades, we witnessed several advances in neuroimaging, each opening new vistas in the exploration of the workings of the human brain. Improvements in brain mapping methods, in particular, now afford us an unprecedented opportunity for studying the structure and function of neural networks, informing our understanding of sensory perception, cognitive processing and motor function. The non-invasive technology of fMRI has revolutionized our understanding of brain function over the last twenty years. fMRI measures the Blood-Oxygen-Level-Dependent (BOLD) signal, which is a function of the hemodynamic and metabolic response to neural activity. This surrogate measure of neural activity can then be used to study brain function in a number of settings. A host of different experimental paradigms have been used to study neural processing, and it is well beyond the scope of this book to do them justice. We therefore have selected a few examples that illustrate promising areas of recent development. The application of novel technologies discussed will allow us to not only elucidate the cortical and subcortical circuits\' mechanisms but also achieve more accurate diagnoses by inducing plasticity or reorganization with the goal to restore injured or diseased brain activity patterns to normal patterns of activity. These advances will foster the development of broader biomedical applications, and will produce a host of associated economic benefits. In addition, introductory chapters of this book (1, 6, and 25) provide basic information to non-experts, such as clinicians and social scientists in the field of brain neuroimaging. The list of chapters is not exhaustive, and we have certainly omitted much more worthy material than it was possible to include. The book has two sections. The Methods section (Section 1), which contains a practical guide to fMRI experiments (chapter 1), and then focuses on select technological advances, such as the neurometabolic underpinnings of BOLD signal dynamics (chapter 2), the promise and limitations of perfusion-based fMRI (chapter 3), the decoding of the phase signal to acquire additional information (chapter 4), the combination of fMRI and EEG measurements and (chapter 5), the ability to combine invasive recording and micro-stimulation methods with fMRI for studying the primate brain (chapter 6), the resting state in the developing brain (chapter 7), as well as maps of cerebellar function (chapter 8). The Applications section (Section 2) presents examples of how recent fMRI methodology can be used to address specific questions about brain function. We discuss latest applications to the visual system (1st subsection: \" Advances in Visual & Auditory Cortical Network Applications\"), such as the development and application of probability- and entropy-based atlases to quantify the inconsistency in localization of human visual areas (chapter 9), the study of perceptual and visual categorization of stimuli using fMRI (chapter 10), the color specificity in the human V4 complex (chapter 11), the developmental plasticity of the human visual system (chapter 12), cross-modal plasticity in blind patients (chapter 13), as well as the potential of real-time fMRI neuro-feedback strategies for enhancing cortical visual rehabilitation (chapter 14). In this 1st subsection, we also discuss the auditory system\'s plasticity and the framework of theoretical and methodological challenges associated with fMRI auditory system studies (chapter 15). The 2nd subsection of the Applications section, \"Advances in Motor Cortical Network Applications\" presents applications of the motor system, including studies of motor imagery as a tool to enhance cognitive and motor performance (chapter 16), the characterization of feedback regulation of limb position using fMRI (chapter 17), and fMRI predictors of surgical outcome (chapter 18). The 3rd subsection of the Applications section, \" Brain Neuroimaging Applications in Disease Processes\" discusses fMRI findings on the pathophysiology underlying Alzheimer’s disease (chapter 19), and hepatic encephalopathy (chapter 20), and examines the use of diffusion-and perfusion-weighted imaging in acute ischemic stroke (chapter 21). The 4th and final subsection of the Applications section, \"Neuroimaging of Decision Making and Social Valuation\" offers a comprehensive review of social neuroscience tasks, aiming to introduce social scientists to fMRI (chapter 22), presents the cortical and subcortical underpinnings of decision making and valuation mechanisms (chapter 23), demonstrates the importance of prediction (as compared to fitting) of behavior in human decision making (chapter 24), and finally elucidates the biological and psychological mechanisms underlying social pain (chapter 25). The brain is the most complex computational device we know, consisting of highly interacting and sometimes redundant networks of areas, supporting specific brain functions. The rules by which these areas organize themselves to perform specific computations have only now started to be uncovered. Advances in neuroimaging already play a critical role in our effort to understand the functional anatomy of distributed cortical circuits and to define how these circuits malfunction in various disease states. The next few years will bring an exponential growth in understanding basic brain processes, largely as a result of further advances in neuroimaging methods and applications. On April 2nd, 2013, the President of the United States of America, Barack Obama unveiled an initiative to map the brain with these words: \"We have a chance to improve the lives of not just millions, but billions of people on this planet through the research that’s done in this BRAIN Initiative alone.\" On the other side of the Atlantic, the European Union has heavily funded the “Human Brain Project” led by Henry Markram at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland. Markram and his team aim to discover “…profound insights into what makes us human, develop new treatments for brain diseases and build revolutionary new computing technologies”. Here we present some recent contributions towards these goals, focusing on the field of human brain neuroimaging and its applications on health and disease. We would like to express our sincere appreciation to all the scientists that contributed to this book, as well as to INTECH publishing company for their valuable and constant assistance. Finally, we would like to whole-heartedly thank the McNair Medical Institute (MMI), the Board of the McNair Medical Institute, and in particular Mr. and Mrs. Robert McNair, the Medical and Scientific Director, neurosurgeon, Dr. Charles Neblett, MMI Board member Ms. Ruth Smith, as well as the MMI Executive Director, Ms. Joanie Haley, whose support made this book possible. We would also like to thank the Ministry of Education of Singapore (AcRF, Tier 1, RG 1/11 M4010946.010) for partially supporting the second editor. T. Dorina Papageorgiou, Ph.D., M.H.Sc. Assistant Professor of Neurology Baylor College of Medicine, U.S.A. George I. Christopoulos, Ph.D., M.Sc. Assistant Professor NBS, Nanyang Technological University, Singapore Research Director, Culture Science Institute, Singapore Stelios M. Smirnakis, M.D., Ph.D. Assistant Professor of Neurology and Neuroscience Baylor College of Medicine, U.S.A.