Modern Approaches to Augmentation of Brain Function

Foreword
Preface
	Human Intellectual Capacity and Its Growth
	Modern Approaches to Brain Augmentation
	Part I: Stimulating the Brain
	Part II: Brain-Computer Interfaces
	Part III: Augmenting Cognitive Function
	Part IV: Futuristic Approaches to Augmentation
	Part V: Augmenting Behavior
	Part VI: Augmenting Cognition and Emotion
	Part VII: Pharmacological Augmentation
Contents
Part I: Stimulating the Brain
	Using Electrical Stimulation to Explore and Augment the Functions of Parietal-Frontal Cortical Networks in Primates
		1 Introduction
		2 Electrical Stimulation: A Selective and Brief History
		3 The Action-Specific Parietal-Frontal Network of Primates
		4 The Functions of the Action-Specific Domains in Primates
		5 The Basal Ganglia: Further Steps in the Action Selection Hierarchy
		6 Using Electrical Stimulation to Augment Action Selection
		References
	Spinal Cord Injury and Epidural Spinal Cord Stimulation
		1 Introduction: Revisiting Low Expectations for Neurological Recovery After “Complete” SCI
		2 Reinterpreting the Lack of Apparent Success of Drugs, Cell Transplants, and Biologics
			2.1 Early Neuromodulation: Electrical Stimulation of Muscle to Restore Function
			2.2 Spinal Cord Stimulation
		3 Concepts that Supported the Testing of Epidural Stimulation for Recovery in SCI
			3.1 Discomplete Spinal Cord Injury
			3.2 Early ES Observations in SCI Subjects to Treat Spasticity
			3.3 Neuroplasticity
			3.4 The Emerging Understanding of Intraspinal Connectivity
			3.5 Intraspinal Circuits for Reciprocating Activity
			3.6 Spontaneous Locomotor Activity Observed After Chronic Human SCI
		4 Epidural Electrical Stimulation, Spinal Cord Injury, and Locomotion
			4.1 Locomotor Activity Resulting from Electrical Epidural Stimulation
			4.2 Locomotor Training and Sensory Input
			4.3 Reported Effects of ES on Autonomic Functions
		5 Transcutaneous Stimulation
		6 Potential ES Synergies
		7 The Essential Role of Spinal Cord Repair Research
		8 Conclusions
		References
	Neurostimulator for Hippocampal Memory Prosthesis
		1 Introduction
		2 Materials and Design
			2.1 Stimulation Pattern Generator Circuit
			2.2 Stimulus Artifact Suppression Technique
			2.3 Electrochemical Properties
			2.4 System Architecture
			2.5 Power Calculation
			2.6 System Cost
		3 Experimental Methods
			3.1 Design Characterization
			3.2 In Vivo Evaluation
		4 Notes
		References
	Modern Approaches to Augmenting the Brain Functions
		1 Introduction
		2 Augmentation Approaches
			2.1 Neuromodulation
			2.2 Brain–Computer Interfaces
			2.3 Futuristic Transfer of Brain Ability
		3 Augmenting Brain Functions
			3.1 Sensory Augmentation
			3.2 Motor Augmentation
			3.3 Augmentation of Cognition
			3.4 Augmentation of Emotions
		4 Clinical Applications
			4.1 Autism
			4.2 Depression
			4.3 Alzheimer’s Disease
			4.4 Post-traumatic Stress Disorder (PTSD)
			4.5 Drug Addiction
			4.6 Parkinson’s Disease
			4.7 Seizures
		5 Technology for Brain Augmentation
			5.1 Neural Engineering
			5.2 Optogenetic Augmentation of Brain Function
			5.3 Neural Nanotechnology
			5.4 Neural Spintronics
			5.5 Tools Advances Based on the Interaction with the Brain
			5.6 Devices for Brain Augmentation
		6 Ethical Issues
		7 Conclusion
		References
Part II: Brain-Computer Interfaces
	Brain Machine Interfaces Within a Critical Perspective
		1 Introduction
		2 Roles in Cognition and Behavior
		3 Sensory-Motor Functions
		4 Ontological Criticalities
		5 Interfacing With the Neural Code
		6 Cascades of Complex Factors
		7 Neuroprothesis and Historical Attempts
		8 Conclusions
		References
	An Implantable Wireless Device for ECoG and Cortical Stimulation
		1 Introduction
		2 Preliminary Experience in Primates
		3 Clinical Applications of Wireless ECoG: Preliminary Experience in Epilepsy Surgery
		4 Conclusions
		References
	BCI Performance Improvement by Special Low Jitter Quasi-Steady-State VEP Paradigm
		1 Introduction
		2 Materials and Methods
			2.1 Continuous Loop Averaging Deconvolution (CLAD)
			2.2 Stimulator and Stimuli Design
			2.3 EEG Recording and Signal Processing
			2.4 Classification
		3 Results
			3.1 ANOVA Results
			3.2 SSVEP Vs. QSS-VEP Comparison
		4 Discussions
		5 Conclusion
		References
	Communication with Brain–Computer Interfaces in Medical Decision-Making
		1 Introduction
		2 Decoding and Communicating
		3 Extracortical and Intracortical BCIs for Communication
		4 Ethical Issues in BCI-Based Communication
		5 A Case Study
		6 Conclusion
		References
Part III: Augmenting Cognitive Function
	Neuroprotection and Neurocognitive Augmentation by Photobiomodulation
		1 Introduction
		2 Part 1: Animal Studies—Prevention of Neurodegeneration and Behavioral Deficits by Photobiomodulation
			2.1 Objectives of Animal Studies of Neuroprotection by Photobiomodulation
			2.2 Significance of Animal Studies of Neuroprotection by Photobiomodulation
			2.3 Cytochrome Oxidase as a Molecular Target of Photobiomodulation
			2.4 In Vitro Neuroprotective Effects of Cytochrome Oxidase Stimulation by Photobiomodulation
			2.5 In Vivo Light Delivery and Dosing Considerations
			2.6 Mitochondrial Dysfunction in Neurodegenerative Disorders and Therapeutic Role of Photobiomodulation
			2.7 Photobiomodulation Prevents Impairment of Visual Function in a Rat Model of Optic Neuropathy Induced by Mitochondrial Dysfunction
			2.8 Photobiomodulation Prevents Structural Retinal Damage in the Model of Optic Neuropathy
			2.9 Protective Effects of Photobiomodulation Are Not Related to Photodegradation of Rotenone
			2.10 Preservation of Visual Function and Retinal Structure Are Not Mediated by Isoflurane Exposure
			2.11 Photobiomodulation Prevents Decreases in Cell Respiration in Brain Homogenates In Vitro
			2.12 Photobiomodulation Increases Brain Antioxidant Capacity in a Dose-Response Manner In Vivo
			2.13 A Single Dose of Photobiomodulation Enhances Brain Cytochrome Oxidase Activity in a Hormetic Fashion In Vivo
			2.14 Fractionated Photobiomodulation Increases Brain Cytochrome Oxidase Activity in a Dose-Response Manner In Vivo
		3 Part 2: Human Studies—Augmentation of Neurocognitive Functions by Photobiomodulation
			3.1 Introduction and Objectives of the Human Studies
			3.2 Significance of Human Cognitive Enhancement by Photobiomodulation
			3.3 Cytochrome Oxidase as Molecular Target for Human Cognitive Enhancement
			3.4 Need to Investigate How TILS Affects Human Neurocognitive Function
			3.5 Overview of Our Approach for Human Cognitive Enhancement by Photobiomodulation
			3.6 Cognitive-Enhancing Effects of TILS of the Human Prefrontal Cortex
				3.6.1 Cognitive Benefits of TILS in Older Participants
			3.7 Neurophysiological Effects of TILS of the Human Prefrontal Cortex
		4 Conclusions
		References
	Avoiding Partial Sleep: The Way for Augmentation of Brain Function
		1 Sleep and “Human Factor”
		2 Peculiarities of Sleep Deprivation Effects
		3 Modern Theories of Sleep
		4 Phenomenon of Partial (Local) Sleep
		5 Partial Sleep and Cognitive Impairments After Sleep Deprivation
		6 Whether Cortical EEG Reflects Peculiarity of Brain Activity in Wakefulness and Sleep, or Just Pattern of the Cortical Afferent Flow?
		7 Which Signals Could Provide Periodic and Synchronous Afferentation During Sleep?
		8 Experimental Validation of the Visceral Hypothesis of Sleep
		9 The Visceral Sleep Theory and Observations of “Slow-Wave” Activity in the Cortical Slabs and Slices
		10 The Pathways for the Visceral Afferentation to the Cerebral Cortex During Sleep
		11 K-Complexes and Visceral Afferentation, Use Dependency, and Sleep Homeostasis
		12 Mechanism of Sleep Initiation and Features of Local Sleep
		13 Conclusion
		References
	Augmentation of Brain Functions by Nanotechnology
		1 Nanotechnologies in Neuroscience
		2 Nanoparticles
		3 Nanoparticle Formulations in the Diagnosis and Therapy of Alzheimer’s Disease
		4 Multimodal Nanoparticles Labeling of Neurons
			4.1 Quantum Dots
		5 Nanoparticle-Based Therapeutics for Brain Injury
		6 Nanotherapeutic Approaches
			6.1 Exosomes as a Communication Tool
		7 Overcoming BBB to Treat Neurodegenerative Diseases
		8 Neuromodulation of the Brain
		9 Noninvasive Neuromodulation by Magneto-Electric Nanoparticles
		10 Nanoelectrical and Chemical Stimulation
		11 Neuroengineering
		12 Sensors
			12.1 Magnetic Tunneling Junctions Sensor
			12.2 Optical Probes for Neurobiological Sensing and Imaging
		13 Biosensors
		14 Neuronal Recording
		15 Multisite Attenuated Intracellular Recordings by Extracellular Multielectrode Arrays
		16 Interface Microelectrodes for Ultrasensitive Monitoring of Alzheimer’s Disease
		17 Resistive Memory Devices
		18 Brain-Machine Interfaces
		19 Conclusion
		20 Future Directions
		References
	The Impact of Aging and Age-Related Comorbidities on Stroke Outcome in Animal Models and Humans
		1 Introduction
		2 The Risk of Cerebral Ischemia Increases with Age
		3 Cerebral Ischemia and Comorbidities
		4 Stroke Models Using Aged Animals Are Clinically More Relevant
		5 Age-Dependent Recovery from Cerebral Ischemia
		6 Spontaneous Stroke Recovery in Aged Patients and Animals
		7 Anti-neuroinflammatory Therapies to Enhance Poststroke Recovery
		8 Cell Therapies
		9 Genetic Conversion Therapy
		10 Conclusion
		References
	Diagnostic Markers of Subclinical Depression Based on Functional Connectivity
		1 Introduction
		2 Experimental Paradigm
		3 Modeling Functional Brain Network
		4 Identification of Dysfunctional Connections
		5 Validating the Model with Machine Learning
		6 Reliable Biomarkers for Subclinical Depression Prediction
		7 Potential for Recovery of Brain Function in Patients with Depression by Transcranial Magnetic Stimulation (TMS)
		8 Comparison to Other Studies
		9 Conclusion
		References
	Transcranial Magnetic Stimulation in Autism Spectrum Disorders: Modulating Brainwave Abnormalities and Behaviors
		1 Introduction
		2 Transcranial Magnetic Stimulation
		3 Outcomes of TMS Studies in Autism
		References
	Neurofeedback Training with Concurrent Psychophysiological Monitoring in Children with Autism Spectrum Disorder with Comorbid Attention Deficit/Hyperactivity Disorder
		1 Introduction
		2 Rationale for Prefrontal Neurofeedback for Gamma Self-Regulation Training
		3 Methods
			3.1 Patient Demographics and Recruitment
			3.2 Behavioral Measures and Evaluations
			3.3 Neurofeedback Protocol and Data Collection
			3.4 The EEG Signal Processing
				3.4.1 Baseline EEG Power Spectrum Analysis
				3.4.2 Measurement of the ANS-Dependent Variables
				3.4.3 Statistical Analysis
		4 Results
			4.1 EEG Activity Measures Across Sessions of Neurofeedback
			4.2 Neurofeedback Training Indexes
			4.3 Autonomic Activity Indexes During Individual Neurofeedback Sessions and Across the Course
			4.4 Behavioral Evaluations
				4.4.1 Consumer Satisfaction Questionnaire (CSQ, Parent Version)
		5 Discussion
			5.1 Consideration of Important Factors During Designing Future Neurofeedback Studies
			5.2 Autonomic Nervous System Activity in Autism
			5.3 Connection Between Central and Autonomic Nervous Systems
		6 Conclusions
		References
Part IV: Futuristic Approaches to Augmentation
	Augmentation Through Interconnection: Brain-Nets and Telemedicine
		1 Brain-Nets
		2 Telemedicine for Neurological Disorders
		3 Future Merger of Telemedicine and Brain-Nets
		References
	Cognitive Augmentation Via a Brain/Cloud Interface
		1 Introduction
		2 Hypothetical Human Brain/Cloud Interface: Premise
			2.1 Quantifying the Human Brain
			2.2 The Neocortex: Tapping Six Layers of Complexity
		3 Precursor Technologies Toward a Brain/Cloud Interface
			3.1 Functionalized Nanomaterials
			3.2 Neural Lace and Nanowires
			3.3 Neural Dust
			3.4 Brain-Machine Interface (BMI)
			3.5 Brainets
			3.6 Photometric Recording of Neural Dynamics
			3.7 Limitations of Current Techniques
		4 Neuralnanorobotic Species: Toward Enabling a Brain/Cloud Interface (B/CI)
			4.1 Endoneurobots
			4.2 Gliabots
			4.3 Synaptobots
			4.4 Wireless Neuralnanorobot Transmitters
		5 Human Brain/Cloud Interface Applications
			5.1 Enhanced Education and Intelligence
			5.2 Reduction of AI-Driven Existential Risk
			5.3 Virtual/Augmented Reality
			5.4 “Transparent Shadowing”
		6 Conclusion
		References
	Augmentation of Neuromarketing by Neural Technology
		1 Introduction
			1.1 Great Advances in Neurotechnology Have Promoted the Development of Economics and Management, Including Marketing
			1.2 Marketing and Its Traditional Research Methods
			1.3 New Technology of the Augmentation of Neuromarketing: Neural Technology
			1.4 The Major Fields of Neuromarketing Augmented by Neural Technology
			1.5 How Does the Neurotechnology Augment Neuromarketing
			1.6 The Important Challenges and the Trends in Neuromarketing
				1.6.1 Three Important Challenges in Neuromarketing
				1.6.2 An important Trends in Neuromarketing: Hyperscanning
		2 The Neural Techniques to Augment Neuromarketing
			2.1 Principles of ERP, fMRI, and fNIRS
			2.2 The Comparison of fMRI, EEG/ERP, and fNIRS
		3 The Major Areas of Marketing Augmented by Neural Technology
			3.1 Brand Perception
			3.2 Facial Attractiveness as an Important Factor to Influence the Perception of Brand
			3.3 Victory or Defeat Affects the Brand Perception
			3.4 Fame of Description Affects Brand Perception
			3.5 Studies on Brand Extension
			3.6 The Perception of Advertisement and the Advertising Design
			3.7 The Perception of Price Affected by Winning or Losing
			3.8 Personalized Design of Products
			3.9 The Fake Rating and the Strategy of Cash Coupons
			3.10 Social Risks Affect Consumers’ Willingness to Buy
			3.11 Luxury Purchases Undermining the Prosocial Behavior: The Cognitive Neural Mechanism Studies
			3.12 How the Sound Frequency and Color Saturation Affect Consumers’ Perception of Product Size
		4 Three Important Challenges in Neuromarketing
		5 Hyperscanning: An Important Trend in Neuromarketing
			5.1 Shift from Single-Brain to MultiBrain Frame
			5.2 Neural Coupling Across Customers
			5.3 Graph Theory-Based Approach Depicting MultiBrain Interactions
			5.4 A Successful Example of Hyperscanning
		References
	Augmentation of Nutrition by Nanotechnology
		1 Nanomaterials and Nanofoods
		2 Nanofoods
		3 Nutrition
		4 Applications of Nanomaterials and Nanodevices in Food Industry
		5 Augmentation of Nutrition
		6 Nanonutrients
		7 Nanotechnology and Its Impact on Food and Nutrition
		8 Nutrition of Plants
		9 Animal Nutrition
		10 Neurotransmitters Produced During Nutrition
		11 Effects on Foods and Nutrition
		12 Protective Roles of Thymoquinone Nanoformulations
		13 Potential Nanonutraceuticals in Human Diseases
		14 Brain–Gut Connectome
		15 Phosphate Binders
		16 Conclusion
		References
	Neural Spintronics: Noninvasive Augmentation of Brain Functions
		1 Introduction
		2 Transcranial Magnetic Stimulation
		3 Neuronal Cable Theory
		4 Programmable Permanent Magnets
		5 Nano-TMS Application to Neuromodulation
		6 Magnetic Tunnel Junctions
		7 Spintronics Approach Involving MTJ-STNOs
		8 High-Resolution Magnetoencephalography (MEG)
		9 Conclusion
		References
Part V: Augmenting Behavior
	Does the Power to Suppress an Action Make Us ‘Free’?
		1 The Irruption of Neurosciences in the Free Will Debate
		2 What Does the Brain Push to Prepare for a Movement If Not the Free Will?
		3 Electric Stimulation of the Posterior Parietal Cortex and of Pre-supplementary Motor Cortex Evoke the Feeling of Intentionality
		4 Is Free Will a Mere Illusion? The Hypothesis of ‘Free Won’t’
		5 What Free Will Is For? Why Does Free Will Could Have Sparked Human Evolution?
		6 Conclusion
		References
	Deep Brain Stimulation for Parkinson’s Disease: Clinical Efficacy and Future Directions for Enhancing Motor Function
		1 Introduction
		2 Deep Brain Stimulation Efficacy in Parkinson’s Disease
			2.1 Deep Brain Stimulation for Motor Symptoms in Parkinson’s Disease
			2.2 Deep Brain Stimulation for Non-motor Symptoms in Parkinson’s Disease
			2.3 Deep Brain Stimulation for the Axial Symptoms in Parkinson’s Disease
		3 Advances in DBS Technology: Robotics, Imaging, and Directional Stimulation
			3.1 Robotic Advances for Stereotactic Surgery
			3.2 Imaging Advances for Surgical Planning
			3.3 Role of Intraoperative Neurophysiology
			3.4 Directional DBS
		4 Closed-Loop DBS: Role of Local Field Potentials to Modulate Brain Function
			4.1 Rationale
			4.2 Potential Biomarkers for Closed-Loop DBS
			4.3 Current Applications
		5 Conclusion
		References
	Neuromodulation for Gait Disorders
		1 Introduction
		2 Key Aspects of Gait: A brief Overview
		3 Neural Control of Locomotion
			3.1 Spinal Mechanisms Controlling Gait: Central Pattern Generators
			3.2 Supraspinal Locomotor Centers
			3.3 Cortical Control of Locomotion
		4 Neurological Gait Disorders
			4.1 Parkinson’s Disease and Freezing of Gait
			4.2 Spinal Cord Injury
			4.3 Age-Related Gait Changes
		5 Invasive Neuromodulation Strategies for Gait
			5.1 Deep Brain Stimulation of the STN and GPi
			5.2 Deep Brain Stimulation of the Mesencephalic Locomotor Region
			5.3 Deep Brain Stimulation of the Substantia Nigra
			5.4 Motor Cortex Stimulation
			5.5 Spinal Cord Stimulation
		6 Noninvasive Neuromodulatory Strategies for Gait
		7 Conclusion and Future Directions
		References
	Augmentation and Rehabilitation with Active Orthotic Devices
		1 Introduction: Background
		2 Advanced Active Orthotic Devices Focusing on Mechatronic/Robotic Exoskeletons and Related Assistive/Therapeutic-Rehabilitative Types of Interventions
		3 Recent Related Systematic Literature Review
		4 Discussion and Conclusions
		References
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
		1 Introduction
		2 Studies of Our Group on Reaction Time, Accuracy, and ERN/Pe in Children with ASD
		3 Application of Transcranial Magnetic Stimulation (rTMS) to Treat ASD
		4 Discussion
		References
	Affective Virtual Reality Gaming for Autism
		1 Introduction
			1.1 Motivation
			1.2 Objectives and Outline
		2 Literature Review
			2.1 Affective Computing
			2.2 Serious Games with VR
			2.3 VR Applications for ASD
		3 Methods
			3.1 Experiments
				3.1.1 Physiological Parameters
					Electrodermal Activity
					Cardiovascular Activity
					Fingertip Temperature (FTT)
				3.1.2 Experiments Using Traditional Media
				3.1.3 Experiments Using Virtual Reality
					Instruments
					VR Contents
					Procedures
					Preliminary Results
					Machine Learning Analysis Approach
			3.2 Game Design
				3.2.1 Game Interaction Modeling
					Affect Recognition Module
					Affect Control Module
			3.3 Customizable User Modeling
			3.4 Graph-Based Adaptivity Modeling
			3.5 Game Application
		4 Discussion and Future Work
		References
	A Machine Learning Approach to Automatic Phobia Therapy with Virtual Reality
		1 Phobias: Statistics, Effects, and Treatment
		2 Virtual Reality in Phobia Therapy
		3 Our Main Contributions
		4 Emotion Models
		5 Biophysical Data
			5.1 Galvanic Skin Response
			5.2 Blood Volume Pulse
			5.3 Electroencephalography
			5.4 Biophysical Data and Virtual Reality
		6 Machine Learning Techniques for Emotion Classification
		7 Our Machine Learning Approach to Classifying the Six Basic Emotions
		8 Our Machine Learning Approach to Fear Level Classification
		9 Fear Level Classification in a VRET System for Acrophobia Therapy
		10 Acrophobia Game in Naturalistic Landscape
		11 Intelligent Virtual Therapist for Acrophobia
		12 Limitations of the Current Research
		13 Limits of Current Phobia Therapy Systems
		14 Proposed Future System
			14.1 Methods and Instruments of Investigation
			14.2 Potential Risks
			14.3 High Future Gains in Phobia Therapy
		References
Part VII: Pharmacological Augmentation
	Vision Augmentation by Pharmacological Enhancement of the Visual Experience
		1 Visual Plasticity: Neural Plasticity and Attentional Processes
			1.1 Organization of the Visual Cortex
			1.2 Plasticity of the Visual Cortex
			1.3 Neuromodulation of Visual Plasticity
				1.3.1 Modulation of Visual Plasticity by Acetylcholine
				1.3.2 Modulation of Visual Plasticity by Monoamines
				1.3.3 Modulation of Visual Plasticity by GABA and Glutamate
		2 Vision Augmentation by Pharmacological Enhancement
			2.1 Vision Augmentation by Cholinergic Drugs
			2.2 Vision Augmentation by Monaminergic Drugs
			2.3 Vision Augmentation by Glutamatergic and GABAergic Drugs
			2.4 Vision Augmentation in Rodents Vs. Humans
		3 Conclusion
		References
	Cognitive-Enhancing Substances and the Developing Brain: Risks and Benefits
		1 Introduction
		2 Cognitive Executive Function and the Prefrontal Cortex
		3 Development of the Prefrontal Cortex and a Potential “Vulnerable Period”
		4 Psychostimulants
		5 Modafinil and Wakefulness-Promoting Drugs
		6 Glutamate-Modulating Drugs
		7 The Future of Cognitive Enhancers
		References
	Pharmacological Approaches in the Augmentation and Recovery of Brain Function
		1 Introduction
			1.1 Substrates of Cognitive Function
			1.2 Pharmacological Modulation of the Endogenous Defense Activity
		2 Pharmacological Agents for Brain Function Enhancement and Recovery
			2.1 Brain Function Enhancement
				2.1.1 Ampakines
				2.1.2 Amphetamines
				2.1.3 Citicoline
				2.1.4 Methylphenidate
				2.1.5 Modafinil
			2.2 Brain Function Recovery
				2.2.1 Amphetamines
				2.2.2 Antidepressants
				2.2.3 Cannabidiol
				2.2.4 Cerebrolysin
				2.2.5 Citicoline
				2.2.6 Curcumin
				2.2.7 Epigallocatechin-3-Gallate (EGCG)
				2.2.8 Levodopa
				2.2.9 Methylphenidate
				2.2.10 NeuroAiD (MLC601, MLC901)
				2.2.11 Piracetam
				2.2.12 Resveratrol
				2.2.13 Sex Hormones
		3 Conclusion
		References
Conclusion
Index