Contemporary Clinical Neuroscience

Series editor

Mario MantoDivision of Neurosciences, Department of Neurology, CHU-Charleroi, Charleroi, Belgium, University of Mons, Mons, Charleroi, Belgium

Contemporary Clinical Neurosciences bridges the gap between bench research in the neurosciences and clinical neurology work by offering translational research on all aspects of the human brain and behavior with a special emphasis on the understanding, treatment, and eradication of diseases of the human nervous system. These novel, state-of-the-art research volumes present a wide array of preclinical and clinical research programs to a wide spectrum of readers representing the diversity of neuroscience as a discipline. The book series considers proposals from leading scientists and clinicians. The main audiences are basic neuroscientists (neurobiologists, neurochemists, geneticians, experts in behavioral studies, neurophysiologists, neuroanatomists), clinicians (including neurologists, psychiatrists and specialists in neuroimaging) and trainees, graduate students, and PhD students.

Volumes in the series provide in-depth books that focus on neuroimaging, ADHD (attention deficit hyperactivity disorder and other neuropsychiatric disorders, neurodegenerative diseases, G protein receptors, sleep disorders, addiction issues, cerebellar disorders, and neuroimmune diseases. The series aims to expand the topics at the frontiers between basic research and clinical applications. Each volume is available in both print and electronic form.

More information about this series at http://www.springer.com/series/7678

Ioan Opris • Mikhail A. Lebedev Manuel F. CasanovaEditors

Modern Approaches to Augmentation of Brain Function

ISSN 2627-535X ISSN 2627-5341 (electronic)Contemporary Clinical NeuroscienceISBN 978-3-030-54563-5 ISBN 978-3-030-54564-2 (eBook)https://doi.org/10.1007/978-3-030-54564-2

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EditorsIoan OprisDepartment of NeurosurgeryUniversity of MiamiMiami, FL, USA

Manuel F. CasanovaGreenville Health SystemUniversity of South CarolinaGreenville, SC, USA

Mikhail A. LebedevCenter for Bioelectrical InterfacesNational Research University Higher School of EconomicsMoscow, Russia

Ioan “John” Opris (1957–2020)

Dr. Ioan Opris, a well-known international scholar and an enthusiast of brain aug-mentation research, passed away in Miami, FL, on October 16, 2020. He is survived by his children Ioan Opris Jr. and Iris Mihaela Opris as well as by his loving wife Anca Liliana Opris.

Ioan Opris was born in Barsana, Maramures County, Romania, and received both his undergraduate and PhD degrees in Physics/Biophysics from the University of Bucharest. In 1990, Ioan began his academic career as an assistant professor within the Faculty of Physics at the University of Bucharest. Years later he would introduce to his university a Master of Neuroscience course and establish together with Professor Ioana Moisil the Romanian Society of Neural Networks. In 1995, Ioan started his neuroscience research in the USA by working with Professor Randall Nelson (University of Tennessee, Memphis) on the role of the neostriatum in coding movement kinematics and motor control. Later work with Professor Vincent Ferrera from Columbia University would lead him to a McDonnell Pew Award (2000) on the neural correlates of decision mechanisms by the prefrontal cortex. He further pursued the work of his McDonnell Pew Award in the laborato-ries of Professors Charles Bruce and Patricia Goldman-Rakic at Yale University. Ioan then moved to Wake Forest University as a scientific researcher in the labora-tory of Dr. Sam Deadwyler. In this laboratory he expanded his expertise of memory prosthetics. Ioan’s academic career began to soar as he participated in several articles demonstrating the functional role of the prefrontal cortical minicolumns in executive control. His studies demonstrated the restoration of cognitive function through a neuroprosthesis that used neural activation specific to the minicolumn in the prefrontal cortex of nonhuman primates. His interest in brain augmentation led to a collection of research publications which won the 2017 Frontiers Spotlight Award.

Ioan’s focus on cortical modularity established him as an heir to Vernon Mountcastle. He used to think of the stereotyped translaminar connections of the cell minicolumn in striking analogy to the quantum jumps of electrons across differ-ent energy levels. This conceptualization propelled Ioan into the exploration of the physics of the mind and brain disorders. This effort culminated in a book for which the Romanian Academy of Sciences bestowed the distinguished Nicolae Simionescu award.

At the time of his death, Ioan was an associate professor at the University of Miami working for the Department of Biomedical Engineering and the Miami Project to Cure Paralysis. Along with Brian Noga, Jim Guest, and Vance Lemon, he studied locomotor behavior using a wide range of tools, including the multichannel recording of brainstem neuronal activity combined with optogenetics and deep brain stimulation.

In his unquenchable curiosity, Ioan Opris was the archetype of the Renaissance man. His mind was always active. He drew ideas from a significant number of com-plex subjects to solve specific problems.

By keeping an open mind, he was always excited about what the world of neuroscience would bring and how he could explore the same. Indeed, according

to Ioan, “It must be a fascinating concert, that of the mind paralleled by the brain’s physiology. I dreamed of articulating for the field this concert for forty years.” We have to believe that in the end his biggest academic regret was that there was so much more left to be explored.

Goodbye good friend, until we meet again,Manny and Misha

Dedication

This book is dedicated to Dr. Jon Howard Kaas who helped to unravel the organiza-tion of the mammalian brain, articulated the workings of many domains of the cere-bral cortex, and promoted the idea of neuroplasticity. It took someone with the skills of a polymath of the neurosciences to mold our views of the sensory and motor brain systems, while revealing how, from an evolutionary standpoint, their organization is altered during brain development. As heir to Socrates in asking all of the pertinent question, Jon Howard Kaas opened the door that many others would follow. Indeed, the field of brain augmentation now solidly stands on the shoulders of a giant.

Many neuroscientists support the reductionist approach; “You, your joys and your sorrows, your memories and ambitions, your sense of personal identity and free will are in fact no more than the behavior of a vast assembly of nerve cells and their associated molecules” (Crick 1995). Jon Kaas and others have proposed a utopian dream where technological advancements will allow us to surpass some of the limitations of our biological brain. External interventions are finally upholding the tenet of the self-help community in that we can do better than we are born with. The static properties of the elemental constituents of the brain are, in this regard, an end to manipulations engendering the emergence of unforeseen properties.

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Foreword

I have been invited to provide a brief introduction to this important volume on mod-ern approaches to augmentation of brain function. Although I am not an expert on this topic and I feel fortunate having been invited to contribute a chapter to this volume, I do have the distinction of having been in the field of neuroscience research for a long time. At the start of my career, there were very few methods and the early generations of computers were very limited. The field was growing, but progress was slow. As technical advances made more approaches viable, rapid progress in understanding of brain organization and function became possible. Yet, there were early efforts to find ways to augment brain functions, especially for those that had sensory impairments. As a prime example, in the days of my postdoctoral training in the laboratory of Clinton Woolsey at the University of Wisconsin in the late 1960s, I was sent to represent the laboratory at a meeting at NIH to discuss the fea-sibility of developing a visual prosthesis as an aid to the blind. The goal was to cre-ate visual images in the blind by directly stimulating primary visual cortex with an array of implanted electrodes. We all know that it did not go well, such that a recent review concluded that the development of a prosthetic device for the blind is still in its infancy. There were obviously many technical issues in the 1960s, and many, but not all, have gone away. One such issue was presented by a speaker who was repre-senting the blind. This I did not anticipate. The speaker said that the blind would not accept a device that required bulky stimulating and processing equipment that would occupy, at the least, a huge backpack. This surprised some researchers and university administrators looking for funds, but it made sense. We are highly social primates, and we all want to fit in. Toward the end of practicality, there has been much progress as the miniaturization of computers, electrode arrays, and other equipment has been one of the signs of great progress. The well-known auditory prosthetic devices have been a huge success as they depend on few stimulating elec-trodes and only access to a sensory nerve rather than to the brain. But even this success took years to develop, and many animal studies. For some of us, including me, the ability to help the hearing impaired so much with only a few electrode sites to stimulate was unexpected, but it worked. The needed number of stimulation sites

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continues to be a problem for augmenting the visual system, where high acuity images are needed.

More recently, as I got to know neurosurgeons at Vanderbilt, I became more aware of the effectiveness of using an implanted electrode to disrupt subcortical circuits that became dysfunctional in Parkinson’s disease. In many adults with this problem, a tremor that interferes with normal hand function is of practical and social concern. In Nashville, I saw a retired professional guitar player suddenly recover his ability to play by turning on his stimulation device. This device greatly improved his quality of life. As a result of this experience, while visiting in northern Wisconsin, I recommended to the best friend of my sister that her brother with a Parkinson tremor inquire about such a subcortical stimulating device. In a subsequent visit, I ran into her by chance, and she told me about the wonderful difference this stimulation device made in her brother’s life.

There is also great hope and expectations for the development of ways to alter, redirect, or focus the functions of the normal brain by electrically stimulating rela-tively few neurons or by stimulating afferent or motor peripheral nerve pathways. Much of this topic is covered in the wonderful chapters of this book, as are other approaches. Some transformations are so simple that we do not even think of them as augmentation. For example, for researchers and others interested in studying the high sound frequency calls of bats, it is a simple matter to record and replay the calls in real time as sounds we can hear. If need be, we can experience sensory stimuli beyond the capabilities of our sensory receptors. And in a plastic brain, experience is always altering brain functions. Thus, understanding how such plasticity is medi-ated, and applying suitable protocols, we can induce and improve desired functions. As I age, I have become more aware of available programs to help me retain mental abilities, but my ability for denial has put off such training. Please enjoy these infor-mative chapters.

Jon H. Kaas Vanderbilt University

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Preface

Human Intellectual Capacity and Its Growth

William James Sidis was born in the United States on April Fool’s Day, 1898, to Jewish emigrants from Ukraine. His father, Boris Sidis, was a prominent psychia-trist who founded the New York State Psychopathic Institute and the Journal of Abnormal Psychology. Boris undoubtedly felt fortunate to escape political prosecu-tion and be accepted by the Boston Society upon his arrival in the United States. Consequently, for Boris, anything seemed possible, and along with his wife, Sarah, they were the prototypical power couple. Sarah, herself, went to Boston University and then graduated from its school of medicine. As they were expanding their social circle, Boris established numerous friendships with the intelligentsia of his time. Indeed, William Sidis’ name came from Boris’ good friend, teacher, and col-league, the famous American philosopher and psychologist William James. More “apropos” with our theme of brain augmentation, Boris became a controversial fig-ure in psychology for his philosophical perspectives on education, believing that an appropriate nurturing environment promoted one’s intellectual capacity. Heredity indeed plays a role, but genius can be created! As its gel-like consistency might betray, the brain is quite a malleable organ and, given proper information, experi-ence, guidance, and discipline, there was a tacit assumption that its full potential could be unleashed. Thus, William Sidis became a well-publicized experiment for the views of his father. As a child prodigy with exceptional mathematical and lin-guistic skills, William entered Harvard University at age 11 and soon became con-versant in 25 different languages. As an observer to the rearing experiment of this precocious child, William James told his audiences that we only use a fraction of our full potential. In this regard William Sidis thus became the rallying cry of a popular culture aimed at changing our minds and therefore our destinies. As John Campbell, a science fiction writer and editor, once said, “no man in all history ever used even half of the thinking part of his brain” (Campbell 1961). From then on, the self-help community believed we could do far better than what we are born with.

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Humans tend to flatter themselves in asserting their uniqueness in the world. Some propose that we are fallen angels rather than risen apes. Indeed, we can all agree that humans do possess many cognitive abilities not seen in any other species. As to an answer for the age old “question of all questions” concerning man’s place in nature, humans are different from other primates by their larger brain in propor-tion to body size, and a frontal cortex that endows them with the capacity for com-plex thought. This wonderful organ accounts for only 3% of the total weight of the human body but consumes 20% of the body’s energy. Given this fact, the reports of early electrophysiologists were puzzling for many scientists. These reports revealed areas of the brain that appeared to be “silent,” that is, not having a recognized func-tion. Wilder Penfield (1891–1976) who expanded neurosurgical techniques and identified the homunculus could not assign a function for a large expanse of the cerebral cortex. This led to a misinterpretation that stemmed from the shortcomings of early electrophysiological experiments; namely, that we only use 10% of our brains.

To clarify, the 10% myth aside, humans use the full extent of their brains all of the time. Contrary to a muscle that is active only during contraction, the brain is continuously active day and night, even during sleep. Our frontal cortex, which is heavily involved in thought and judgment while we are awake, mediates normal sleep physiology and is intimately involved in the sleep-deprivation phenomena. However, akin to muscles, the brain can be trained to improve its capabilities, encompassing memory, attention, and learning. Accepting the fact that brain function can be improved, the more crucial question remains as to whether they can also be enhanced.

Modern Approaches to Brain Augmentation

The brain is a biophysical system that consists of hundreds of billions of elements, called neurons, interconnected through the connectome into neuronal circuits that perform complex information processing and generate network states dynamically distributed across the entire brain. The operation of brain circuitry is governed by the fundamental laws of physics, such as minimization of entropy under the princi-ples of hierarchical dynamics. Brain dysfunctions—exorbitantly costly, both eco-nomically and sociologically—damage the fine and sophisticated brain architecture and lead to debilitating disorders. We are witnessing the explosive development of highly technological methods for brain diagnostics and therapeutics, such as neuro-imaging techniques and nanotechnology. These new technologies hold promise to revolutionize medicine and lead to remedies to severe neurological conditions pre-viously deemed uncurable. In addition to clinically relevant applications, these technologies facilitate the advancement of fundamental Neuroscience and bring us closer to resolving the greatest challenge in science—elucidation of brain functionality.

Modern neural technologies are also applicable to augmenting brain functions in healthy humans—the idea that belonged exclusively to the realm of science fiction

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not so long ago but currently is becoming a reality owing to the advances in Neuroscience and Neuroengineering. Augmentation technologies have emerged in sensory, motor, and cognitive domains, and if they become both safe and efficient it is likely that they will become widespread. The development of augmentation tech-nologies takes place on different scales—micro- and macrocircuits of the brain—and with different recording/stimulation methods, some invasive and some noninvasive. This book overviews the existing and emerging methods for brain aug-mentation; a multiplicity of approaches are discussed.

If Ray Kurzweil is correct and we are approaching singularity (Kurzweil 2005), brain augmentation technologies can be viewed as an advancement toward a merger between the brain and machines, the development that will cause irreversible changes in society. This book describes the recent trends in this direction. Different chapters in this book cover advances in the neural sciences by which we can enhance sensory, motor, and cognitive functions, as well as mood and emotions. Additionally, insights are made into the application of brain augmentation approaches to the treat-ment of devastating neural disorders such as spinal cord injury, Parkinson’s disease, depression, dementia, and autism. Given the potential impact of brain augmentation approaches on the society, it was also important to discuss the philosophical and ethical issues arising from the use of technologies to enhance neural processing of information, memory, attention, and emotions.

The book is organized in seven parts containing 30 chapters. The Introduction is written by Professor Jon Howard Kaas, member of the US Academy of Sciences. The seven parts are summarized below.

Part I: Stimulating the Brain

A multitude of neurostimulation methods have emerged during the last several decades for treating neural disorders, rehabilitation, and brain augmentation, includ-ing electromagnetic and optogenetic stimulation and pharmacological approaches. Jon H. Kaas and Iwona Stepniewska open this narrative by laying down the idea that brain functions can be directly augmented by electrically stimulating ensembles of neurons to potentiate their actions. Their chapter (Chap. 1) is entitled “Using Electrical Stimulation to Explore and Augment the Functions of Parietal-Frontal Cortical Networks in Primates.”

Jim Guest and his colleagues in the chapter entitled “Multi-system Benefits of Epidural Stimulation Following Spinal Cord Injury” (Chap. 2) describe recent epi-dural stimulation discoveries that have changed our understanding of the capabili-ties of the spinal cord, leading to a shift away from detailed hierarchical cortical and brainstem control of spinal function to one in which the spinal cord itself executes complex locomotor programs.

Elyahoodayan and his colleagues address the possibility of building prosthetic memory using neurostimulation. In Chap. 3, “Neurostimulator for Hippocampal Memory Prosthesis,” they describe a neurostimulator design that is desirable in a

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variety of neural interface applications, particularly hippocampal memory prosthe-sis aiming to restore cognitive functions by reinstating neural code transmissions in the brain.

In Chap. 4 entitled “Modern Approaches to Augmenting the Brain Functions,” Opris and his colleagues review a range of augmentation approaches based on stim-ulation, including neuromodulation, pharmacological methods, brain-computer and brain-to-brain interfaces. The chapter covers recent advances in neural technolo-gies, such as microtechnology, spintronics, nanotechnology, optogenetics, and min-imally invasive electrode arrays.

Part II: Brain-Computer Interfaces

Brain-computer interfaces are artificial systems that connect the brain with external devices, such as limb prostheses and means of communication. Brain-computer interfaces are applicable to both treatment of patients and brain augmentation in healthy people. In the opening chapter for this part, Chap. 5 entitled “Brain Machine Interfaces Within a Critical Perspective,” Zippo and Biella describe the brain as a complex mechanistic machinery that executes functions and processes information. Brain-computer interfaces either enable invasive physical communication between the nervous system and the artificial devices or noninvasive communication using recording methods such as electroencephalography and magnetoencephalography, and stimulation methods such as transcranial magnetic stimulations.

In Chap. 6 entitled “An Implantable Wireless Device for ECoG and Cortical Stimulation,” Romanelli describes the first prototype of a wireless ECoG system that provides an innovative approach to detect seizure foci in medically refractory epilepsy and to perform BCI procedures.

Kaya, Bohorquez, and Özdamar continue the theme of brain-computer interfaces with the chapter entitled “BCI Performance Improvement by Special Low Jitter Quasi-Steady State VEP Paradigm” (Chap. 7). Visual Evoked Potential (VEP) based brain-computer interfaces are common because of their ease of implementation and a number of advantages. Recently, transient VEP retrieval from linear regression and random code estimation has gained attention as a brain interface method. When applied to electroencephalographic recordings, this method improves the perfor-mance of brain-computer interfaces.

In Chap. 8 entitled “Communication with Brain-Computer Interfaces in Medical Decision-Making,” Glannon argues that brain-computer interfaces can restore or augment motor functions that have been impaired or lost from traumatic brain injury and neurodegenerative disease. The author discussed how “locked-in” patients and some patients in the minimally conscious state could use a brain-computer interface to express consequential decisions about life-sustaining therapy.

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Part III: Augmenting Cognitive Function

The possibility of augmenting cognitive functions with neural technologies has received considerable attention. Gonzalez-Lima contributes Chap. 9, “Neuroprotection and Neurocognitive Augmentation by Photobiomodulation,” where animal and human studies are described using red to near-infrared lasers and LEDs, a noninvasive and relatively inexpensive intervention, which are applicable to neuroprotection and for the augmentation of cognitive brain functions.

In Chap. 10 entitled “Avoiding Partial Sleep: The Way for Augmentation of Brain Function,” Pigarev and Pigareva describe a study that demonstrates that cortical areas that process signals from extero- and proprioreceptors during wakefulness switch to the processing of interoceptive information during sleep. They suggest that during sleep the computational power of the brain is directed to the restoration of the vital functions of internal organs.

In Chap. 11, “Augmentation of Brain Functions by Nanotechnology,” Opris and his colleagues describe an unprecedented increase that occurred during the last decade in the successful application of nanotechnology methods to basic neurosci-ence and to clinical practice. The authors review how nanotechnology (nanoparti-cles, nanowires, carbon nanotubes, devices, sensors, interfaces) is employed to augment, record, stimulate, repair, and regenerate brain circuits.

Chapter 12, “The Impact of Aging and Age-Related Comorbidities on Stroke Outcome in Animal Models and Humans,” written by Popa-Wagner and his col-leagues, makes parallels between animal models of stroke and clinical data and summarizes the impact of aging and age-related comorbidities on the efficacy of various therapies and stroke outcome. The authors conclude that the unsuccessful bench-to-bedside translation of therapies that showed efficacy in young animal models, to aged stroke comorbid patients, is, most likely, due to the negative impact of comorbidities and advanced age on the efficacy of restorative therapies.

In Chap. 13 entitled “Diagnostic Markers of Subclinical Depression Based on Functional Connectivity,” Zhu, Bohorquez, and Opris review the subclinical depres-sion prediction model that detects abnormal functional connections through machine learning. Overall, it is concluded that functional connection analysis based on the thalamus and habenula nucleus can provide a high-accuracy biomarker of subclini-cal depression.

Casanova and his colleagues continue with Chap. 14, “Transcranial Magnetic Stimulation in Autism Spectrum Disorders: Modulating Brainwave Abnormalities and Behaviors,” where they describe how transcranial magnetic stimulation (TMS), especially at low frequencies, has proven to be a safe intervention for children with ASD. This is the first treatment targeting a core pathological abnormality of autism. Outcome measures reveal improvements in executive functions as shown by a nor-malization of error monitoring (i.e., detection, evaluation, and correction of errors) and attendant ERP components.

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In Chap. 15, “Neurofeedback Training with Concurrent Psychophysiological Monitoring in Children with Autism Spectrum Disorder with Comorbid Attention Deficit/Hyperactivity Disorder,” Sokhadze and his colleagues suggest that neuro-feedback training can be used as a treatment modality of potential use for improving self-regulation skills in autism spectrum disorder (ASD). They report significant reduction in irritability and hyperactivity subscales of the ABC, decrease of T-score on SRS-2, and decrease in attention deficits scores.

Part IV: Futuristic Approaches to Augmentation

Some approaches to brain augmentation are futuristic, but still feasible. In Chap. 16, entitled “Augmentation Through Interconnection: Brain-Nets and Telemedicine,” Lebedev and his colleagues discuss the futuristic approach to brain augmentation based on brain-nets comprising several brains connected into a network that enacts information exchange between several subjects. Brain-nets have extended the bidi-rectional brain-computer interface approach, where information is extracted from brain activity simultaneously with the delivery of information to the brain with neurostimulation. Furthermore, Lebedev and his colleagues discuss how brain-nets could be used in telemedicine. The authors foresee that brain-nets and telemedicine will merge to advance new, highly effective neurotechnologies.

In Chap. 17, “Cognitive Augmentation via a Brain/Cloud Interface,” Angelica, Opris, and Boehm review the future discipline of neural nanorobotics that sets the goal of developing nanorobotic species designated as endoneurorobots, gliabots, and synaptobots that hold promise to facilitate a direct and seamless interface between the human neocortex and the cloud/edge, referred to as a Brain/Cloud Interface (B/CI). This chapter explores these paradigm-shifting possibilities for cognitive augmentation toward envisioning what may be possible within the next few decades.

Ma et al. contribute the chapter “Augmentation of Neuromarketing by Neural Technology” (Chap. 18) where they suggest that marketing and management are fundamental economic activities rooted in the cognitive abilities of the human brain. In this regard, decision-making is a cognitive process of selecting the best option between two or more options. The main research areas discussed in the chapter include augmentation of neuromarketing, neuromanagement, neuro-information systems, decision neuroscience, and neuroeconomics.

In Chap. 19, “Augmentation of Nutrition by Nanotechnology,” Sonea, Lupusoru, and Opris provide insights into the augmentation of nutrition process by means of nanotechnology. This technology has evolved more toward the food industry in the domains of food production, processing, conservation, packaging, safety, sensing, functional food, and nutraceutical delivery.

In Chap. 20, “Neural Spintronics: Noninvasive Augmentation of Brain Functions,” Barnes et al. review the emerging field of Spintronics that is attracting a lot of atten-tion with its noninvasive abilities to sense the magnetic field of neurons and to

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modulate their firing with spintronics devices. Two such tools are critical: transcra-nial magnetic stimulation (TMS), and magnetic encephalography (MEG). Nano- TMS/MEG devices can be used in a broad range of research fields and technological medical applications where programmable focusing magnetic field is required.

Part V: Augmenting Behavior

The part on augmenting behavior starts with the chapter by Mirabella, entitled “Does the Power to Suppress an Action Make Us Free?” (Chap. 21). Mirabella notes that there are still no clear answers to the problem of free will. Yet, the bottom- up approach of neuroscience seems to be more promising than that of philosophy, which is deductive or top-down by nature. Overall, the experimental evidence gath-ered so far suggests that, except specific medical conditions, we are free of choosing how to act as much as we are responsible for what we do.

In Chap. 22, “Deep Brain Stimulation for Parkinson’s Disease: Clinical Efficacy and Future Directions for Enhancing Motor Function,” Luca and his colleagues discuss the method of deep brain stimulation (DBS) that produces a significant improvement in motor symptoms in patients with advanced Parkinson’s disease (PD). Recent advances in technology provide the ability to deliver stimulation adaptively based on cortical and subcortical brain signals, and subsequently a more physiological and precise modulation of the impaired motor network.

Chapter 23, “Neuromodulation for Gait Disorders,” written by Chang and his colleagues, provides an overview of the neurophysiology and pathophysiology of common gait disorders. The authors review the most promising invasive and nonin-vasive strategies being investigated to augment one of our most fundamental daily activities—walking.

Onose and his colleagues contribute the chapter “Augmentation and Rehabilitation with Active Orthotic Devices” (Chap. 24), where they address the treatment meth-ods for severe disabilities caused by lesions to the nervous systems. Such conditions are a major health and socio-economic problem and a challenge to scientific research. The authors argue that active orthotic devices are an emerging domain for augmenting function in disabled patients.

Part VI: Augmenting Cognition and Emotion

Cognition and emotion can be augmented with neural technologies. In Chap. 25, entitled “Effects of rTMS on Behavioral and Electrocortical Measures of Error Monitoring and Correction Function in Children with Autism Spectrum Disorder,” Sokhadze and his colleagues suggest that error monitoring and correction is one of the executive functions that is important for effective goal-directed behavior. The chapter provides rationale to use ERN and Pe, along with behavioral performance

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measures as functional outcome measures to assess the effectiveness of neuromodu-lation (e.g., rTMS and rTMS combined with neurofeedback) in children with autism and thus may have important practical implications.

Chapter 26, “Affective Virtual Reality Gaming for Autism,” written by Li and his colleagues, reviews emotional impairment, which is one of the common symptoms of many mental diseases. Being able to learn the emotional reactions from subjects using nonintrusive human-computer interactions (HCI) would provide a novel and efficient approach to assist existing intervention and therapy. Psychologists con-ducted research using virtual reality (VR) as a tool for exposure starting from decades ago. This chapter reviews the methodologies commonly used in affective computing and related research projects using VR exposure as an intervention for people with special needs.

Bălan, Moldoveanu, and Leordeanu provide Chap. 27, “A Machine Learning Approach to Automatic Phobia Therapy with Virtual Reality.” The authors present a new automated approach to phobias therapy, based on the integration of virtual real-ity technology, artificial intelligence, and affective computing—the ability of com-putational machines to recognize, adapt, and respond intelligently to human emotions.

Part VII: Pharmacological Augmentation

Pharmacological agents have been long explored as an approach to treat neurologi-cal disorders and augment the brain of healthy people. In Chap. 28, “Vision Augmentation by Pharmacological Enhancement of the Visual Experience,” Vaucher reviews the research examining whether potentiation of the central cholinergic and/or monoaminergic systems aids visual perception and restoration. Vaucher argues that irreversible vision can be prevented by combining visual training with com-mercially available pharmacological agents.

In Chap. 29, “Cognitive Enhancing Substances and the Developing Brain: Risks and Benefits,” Urban and Gao discuss the current trends in cognitive enhancement among adolescents and adults. The authors examine several prescription drugs com-monly used or being examined for their potential cognitive enhancing effects and discuss the potential risks of each substance. They also discuss the state of over-the- counter nootropics and the lack of reliable research into their efficacy and safety.

In the last chapter of the book, Chap. 30, entitled “Pharmacological Approaches in the Augmentation and Recovery of Brain Function,” Mureșanu and his colleagues describe several pharmacological brain enhancers and assess their capacity to sup-port the brain’s endogenous defense mechanisms.

Miami, FL, USA Ioan Opris Moscow, Russia Mikhail A. Lebedev Greenville, SC, USA Manuel F. Casanova

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Contents

Part I Stimulating the Brain

Using Electrical Stimulation to Explore and Augment the Functions of Parietal- Frontal Cortical Networks in Primates . . . . . . . . . . . . . . . . . . . 3Jon H. Kaas and Iwona Stepniewska

Spinal Cord Injury and Epidural Spinal Cord Stimulation . . . . . . . . . . . . 19Andrea J. Santamaria, Pedro M. Saraiva, Stephano J. Chang, Ioan Opris, Brian R. Noga, and James D. Guest

Neurostimulator for Hippocampal Memory Prosthesis . . . . . . . . . . . . . . . 39Sahar Elyahoodayan, Wenxuan Jiang, Huijing Xu, and Dong Song

Modern Approaches to Augmenting the Brain Functions . . . . . . . . . . . . . . 57Ioan Opris, Brian R. Noga, Mikhail A. Lebedev, and Manuel F. Casanova

Part II Brain-Computer Interfaces

Brain Machine Interfaces Within a Critical Perspective . . . . . . . . . . . . . . 93Antonio G. Zippo and Gabriele E. M. Biella

An Implantable Wireless Device for ECoG and Cortical Stimulation . . . . 111Pantaleo Romanelli

BCI Performance Improvement by Special Low Jitter Quasi-Steady-State VEP Paradigm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121Ibrahim Kaya, Jorge Bohorquez, and Özcan Özdamar

Communication with Brain–Computer Interfaces in Medical Decision- Making . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141Walter Glannon

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Part III Augmenting Cognitive Function

Neuroprotection and Neurocognitive Augmentation by Photobiomodulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165Francisco Gonzalez-Lima

Avoiding Partial Sleep: The Way for Augmentation of Brain Function . . . 209Ivan N. Pigarev and Marina L. Pigareva

Augmentation of Brain Functions by Nanotechnology . . . . . . . . . . . . . . . . 233Ioan Opris, Nicholas Preza, Mikhail A. Lebedev, Brian R. Noga, Stephano J. Chang, Manuel F. Casanova, Mircea Lupusoru, Victor M. Pulgar, Sakhrat Khizroev, Jorge Bohorquez, and Aurel I. Popescu

The Impact of Aging and Age-Related Comorbidities on Stroke Outcome in Animal Models and Humans . . . . . . . . . . . . . . . . . . 261Aurel Popa-Wagner, Mircea Popescu-Driga, and Daniela Glavan

Diagnostic Markers of Subclinical Depression Based on Functional Connectivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283Yunkai Zhu, Jorge Bohorquez, and Ioan Opris

Transcranial Magnetic Stimulation in Autism Spectrum Disorders: Modulating Brainwave Abnormalities and Behaviors . . . . . . . . . . . . . . . . . 297Manuel F. Casanova, Ioan Opris, Estate M. Sokhadze, Emily L. Casanova, and Xiaoli Li

Neurofeedback Training with Concurrent Psychophysiological Monitoring in Children with Autism Spectrum Disorder with Comorbid Attention Deficit/Hyperactivity Disorder . . . . . . . . . . . . . 311Estate M. Sokhadze, Desmond P. Kelly, Eva Lamina, and Manuel F. Casanova

Part IV Futuristic Approaches to Augmentation

Augmentation Through Interconnection: Brain-Nets and Telemedicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343Mikhail A. Lebedev, Igor A. Shaderkin, Ilia V. Ryabkov, and Georgy S. Lebedev

Cognitive Augmentation Via a Brain/Cloud Interface . . . . . . . . . . . . . . . . . 357A. Angelica, I. Opris, Mikhail A. Lebedev, and F. J. Boehm

Augmentation of Neuromarketing by Neural Technology . . . . . . . . . . . . . 387Qingguo Ma, Jia Jin, Tao Liu, and Xiaoyi Wang

Augmentation of Nutrition by Nanotechnology . . . . . . . . . . . . . . . . . . . . . . 415Cosmin Sonea, Mircea Lupusoru, and Ioan Opris

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Neural Spintronics: Noninvasive Augmentation of Brain Functions . . . . . 433Stewart E. Barnes, Ioan Opris, Brian R. Noga, Sunxiang Huang, and Fulin Zuo

Part V Augmenting Behavior

Does the Power to Suppress an Action Make Us ‘Free’?. . . . . . . . . . . . . . . 449Giovanni Mirabella

Deep Brain Stimulation for Parkinson’s Disease: Clinical Efficacy and Future Directions for Enhancing Motor Function . . . . . . . . 463Corneliu C. Luca, Joacir Graciolli Cordeiro, Iahn Cajigas, and Jonathan Jagid

Neuromodulation for Gait Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 485Stephano J. Chang, Ioan Opris, James D. Guest, and Brian R. Noga

Augmentation and Rehabilitation with Active Orthotic Devices . . . . . . . . 521Gelu Onose, Maria Veronica Morcov, Corina Sporea, Andrada Mirea, and Vlad Ciobanu

Part VI Augmenting Cognition and Emotion

Effects of rTMS on Behavioral and Electrocortical Measures of Error Monitoring and Correction Function in Children with Autism Spectrum Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551Estate M. Sokhadze, Ioan Opris, Lonnie Sears, Ayman S. El-Baz, Allan Tasman, and Manuel F. Casanova

Affective Virtual Reality Gaming for Autism . . . . . . . . . . . . . . . . . . . . . . . . 575Yi (Joy) Li, Estate M. Sokhadze, Hao (Irene) Luo, Ayman S. El-Baz, and Adel S. Elmaghraby

A Machine Learning Approach to Automatic Phobia Therapy with Virtual Reality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607Oana Bălan, Alin Moldoveanu, and Marius Leordeanu

Part VII Pharmacological Augmentation

Vision Augmentation by Pharmacological Enhancement of the Visual Experience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 639Elvire Vaucher

Cognitive-Enhancing Substances and the Developing Brain: Risks and Benefits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 661Kimberly R. Urban and Wen-Jun Gao

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Pharmacological Approaches in the Augmentation and Recovery of Brain Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 679Dafin F. Mureșanu, Codruța Bîrle, Livia Livinț Popa, Olivia Verișezan- Roșu, and Ștefan Strilciuc

Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 719

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 721

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