Neuromodulation : comprehensive textbook of principles, technologies, and therapies. Volume 1 / edited by Elliot S. Krames, P. Hunter Peckham, Ali R. Rezai

NEUROMODULATION List of Contributors Foreword Volume 1 Volume 2 Volume 3 Other Neuromodulation Definitions and Terms References Further Reading XII Neuromodulation for Functional Restoration INTRODUCTION References 93 - The History of Neuromuscular Electrical Stimulation—The Evolution of Functional Neuromuscular Stimulation and Future Directions References Further Reading 94 - Functional Electrical Stimulation for Return of Function After Stroke Introduction Upper-Limb Applications NMES Applications FES Applications Lower-Limb Applications NMES Applications FES Applications Shoulder Pain Surface NMES Percutaneous and Implanted NMES Conclusions Acknowledgments References 95 - Invasive Neurostimulation for Poststroke Motor Recovery Introduction Proposed Mechanisms Underlying Functional Recovery Neurostimulation-Based Approaches to Enhance Motor Poststroke Motor Recovery Noninvasive Brain Stimulation Vagal Nerve Stimulation (VNS) Epidural Cortical Stimulation Deep Cerebellar Stimulation Future Trends and Pathways Conclusion References 96 - Stimulation for Return of Upper-Extremity Function Historical Perspective Pertinent Anatomy, Physiology, and Disease Pathophysiology Rationale for Neuromodulation Target Selection and Approach Indications and Patient Selection Criteria Technology Description and User Control Implant Procedure Details Programming and Other Points of Consideration Outcomes First-Generation Implanted Upper-Extremity Neuroprostheses (IRS-8) Second-Generation Implanted Upper-Extremity Neuroprostheses (IST-10+IJAT) Second-Generation Implanted Upper-Extremity Neuroprostheses (IST-12+MES) Second-Generation Implanted Upper-Extremity Neuroprostheses (High Tetraplegia) Complications and Avoidance What the Future Holds Conclusions References Further Reading 97 - Lower Extremity Motor System Neuroprostheses Neuroprosthetic Options for Restoring or Improving Ambulation Neuroprostheses for Walking After Incomplete Paralysis Neuroprostheses for Walking After Complete Paralysis Hybrid Neuromechanical Systems Powered Exoskeletons Future Directions and Challenges Neuroprostheses for Controlling Seated and Standing Balance Neuroprosthetic Interventions for Truncal Stability and Active Sitting Application of Continuous Stimulation Context-Dependent Stimulation Future Directions and Challenges Automatic Control of Standing Balance Future Directions and Challenges Neuroprostheses for Recreation and Exercise References 98 - Neuromodulation of the Spinal Cord for Movement Restoration Historical Perspective Spinal Cord Epidural Stimulation Facilitates Stepping and Standing in Mammals Evidence of Sophisticated Neural Networks in the Human Spinal Cord Circuitry Spinal Cord Epidural Stimulation Facilitates Standing and Stepping Patterns in Humans Spinal Cord Epidural Stimulation Evoked Unforeseen Voluntary Movement Responses and Independent Standing in Humans With Motor-Co... Rationale for Neuromodulation Target Selection and Approach Programming and Other Points of Consideration Voluntary Movement Selection of Epidural Stimulation Parameters for Promoting Voluntary Leg and Trunk Movement Role of Activity-Based Training With Spinal Cord Epidural Stimulation for Recovery of Motor Function for Voluntary Leg and Trunk... Standing Selection of Epidural Stimulation Parameters for Promoting Standing Role of Activity-Based Training With Spinal Cord Epidural Stimulation for the Recovery of Motor Function for Standing Stepping Selection of Epidural Stimulation Parameters for Promoting Standing Role of Activity-Based Training With Spinal Cord Epidural Stimulation for Recovery of Motor Function for Step Training Summary and Future Directions References 99 - A Brief History of the Cochlear Implant and Related Treatments Introduction Steps Toward Ever-Better Hearing With Cochlear Implants and Related Treatments Steps 1–3: From Proof-of-Concept Demonstrations to Multisite Implants Status of the Field as of the Late 1980s Step 4: Better Processing Strategies Status of the Field as of the Mid-1990s Step 5: Adjunctive Stimulation The Steps Reprised and the Growth in the Number of Implants Over the Years Comment About Medical (and Other) Breakthroughs Recognitions of the Achievement The Future Dedication Acknowledgments References 100 - Stimulation for the Return of Hearing Design of Cochlear Implants Aspects of Normal Hearing Loss of Hearing Electrical Stimulation of the Auditory Nerve Components of Cochlear Implant Systems Transformation of Input Sounds Into Stimuli for the Implant Performance With the Present-Day Unilateral Implants Adjunctive Stimulation Possibilities for the Future Acknowledgments References 101 - The Development of Visual Prosthetic Devices to Restore Vision to the Blind Epiretinal Prostheses Second Sight Medical Products EpiRet Intelligent Medical Implants Subretinal Prostheses Optobionics Retina Implant AG Boston Retinal Implant Project Stanford University Suprachoroidal Prostheses Bionic Vision Australia Department of Visual Science, Osaka University Summary References 102 - Neuromodulation for Treatment of Dry Eye Overview of Dry Eye Disease Signs, Symptoms, and Diagnosis of Dry Eye Epidemiology of Dry Eye Disease Physiology of the Ocular Surface Tears Tear Film Lipid Layer Aqueous Layer Mucin Layer Tear Dynamics Pathophysiology of Dry Eye Disease Role of Inflammation in Dry Eye Anatomy and Physiology of the Lacrimal Functional Unit Oculolacrimal Neural Pathway Nasolacrimal Reflex Pathway Pathophysiology of the Lacrimal Functional Unit The Intranasal Tear Neurostimulator Clinical Outcomes With the Intranasal Tear Neurostimulator in Dry Eye Effects on Aqueous Tear Production Effects on Tear Components, Goblet Cell and Meibomian Gland Activity Safety of the Intranasal Tear Neurostimulator Conclusions Acknowledgments References 103 - Neuroprostheses for Restoring Sensation Introduction Somatosensation for Prostheses Benefits Body-Powered Versus Electrically Powered Prostheses and Somatosensation Neural Interfaces Are Needed to Restore Somatosensation Peripheral Nerve Interfaces Stimulation Parameters and Patterns Class III Medical Device Status Clinical Demonstrations of Somatosenstory Restoration Summary References XIII A - Neuromodulation for Cardiovascular Disorders INTRODUCTION References 104 - Autonomic Control of the Heart Cardiac Afferent Neurons Cardiac Efferent Neurons Local Circuit Neurons Interactions Among Autonomic Neurons in the Coordination of Regional Cardiac Indices Overview Intrinsic Cardiac Neuronal Interactions Intrathoracic Extracardiac Reflexes Central-Peripheral Reflex Interactions in the Coordination of Cardiac Indices Cardiac Autonomic Dysfunction Secondary to Cardiac Pathology Conclusion References 105 - Spinal Cord Stimulation for Peripheral Vascular Disorders Introduction History of Electrical Stimulation for Peripheral Arterial Disease Indications and Patient Selection Criteria Trial Stimulation and Programming in Peripheral Arterial Disease Patients Outcomes Conclusion and Future Expectations References Further Reading 106 - Neuromodulation for Refractory Angina and Heart Failure Neuromodulation for Refractory Angina Pectoris Definition, Pathology, and Symptomatology of Angina Pectoris Conventional Treatment for Angina Pectoris Lifestyle Modification and Pharmacological Treatment Revascularization Refractory Angina Pectoris Definition Incidence and Prevalence Patient Characteristics Treatment of Refractory Angina Pectoris Historical Perspective of Neuromodulation in Angina Pectoris Implant Procedure and Stimulation Regime Implant Procedure Stimulation Regime Review of the Most Recent Literature Safety and Preclinical Studies of Neuromodulation for Myocardial Ischemia Long-Term Effects of Spinal Cord Stimulation Placebo-Controlled Trials Randomized Trials of Spinal Cord Stimulation Versus Other Treatment Modalities Registry Studies Systematic Reviews Clinical Perspective Patient Selection Follow-Up Complications of Spinal Cord Stimulation for Refractory Angina Pectoris Device Interactions Neuromodulation for Heart Failure Definition, Pathology, Symptomatology and Treatment of Heart Failure Preclinical Studies of Spinal Cord Stimulation in Heart Failure Clinical Studies of Spinal Cord Stimulation in Heart Failure Future Perspectives (The Next Five Years) Conclusions References 107 - Baroreceptor Activation for Hypertension and Heart Failure Hypertension: Prevalence and Population Health The Pathophysiology of Hypertension Targeting the Sympathetic Nervous System With Modulatory Therapies Baroreflex Activation Therapy Trial Data Device-Based Therapy in Hypertension Trial Rheos Pivotal Trial Long-Term Rheos Pivotal Trial Patient Follow-Up Barostim Neo Trial Carotid Nitinol Device (MobiusHD) Heart Failure: Prevalence and Population Health Pathophysiology of Heart Failure Heart Failure and the Role of Baroreflex Activation Therapy The Barostim HOPE4HF (Hope for Heart Failure) Study Long-Term Chronic Baroreflex Activation in Heart Failure With Reduced Ejection Fraction Discussion and Future Directions Conclusions References XIIII B - NEUROMODULATION FOR PULMONARY DISORDERS INTRODUCTION 108 - Upper Airway Neurostimulation to Treat Obstructive Sleep Apnea Background of the Clinical Problem Epidemiology Mechanisms Current Therapy Physiologic Studies Supporting Neuromodulation Therapy Tongue Musculature and Hypoglossal Nerve (HN) Control Transcutaneous Electrical Stimulation (TES) of Upper Airway Muscles Initial Demonstration of Hypoglossal Nerve Stimulation (HNS) Development of Implantable Devices: 2001–13 Closed-Loop Hypoglossal Neurostimulation Devices Open-Loop Hypoglossal Neurostimulation Devices Regulatory Trials of Hypoglossal Nerve (HN) Devices FDA-Approved Inspire II UAS for OSA in Clinical Use The Inspire Upper Airway System (UAS) Clinical Selection Criteria Safety Summary for All Devices Safety Other Outcome Measures for Efficacy Sleep Architecture Daytime Sleepiness and Sleep-Related Quality of Life (QOL) Therapy Acceptance and Adherence Future Directions Mechanisms and Effects of Stimulation on Upper Airway Physiology Development of a Preclinical Model for OSA Improvements in Neurostimulation Devices Longitudinal Studies of OSA Treated With Hypoglossal Neurostimulation Conclusion Acknowledgments References 109 - A Neural Prosthesis for Obstructive Sleep Apnea Introduction Control of Airway Patency Through Tongue Muscles Prosthetic Design for Obstructive Sleep Apnea (OSA) Single Electrode Closed-Loop Prosthesis Design for Obstructive Sleep Apnea Obstructive Sleep Apnea Prosthesis With Selective Stimulation Clinical Implementation Conclusion Acknowledgment References 110 - Transvenous Phrenic Nerve Stimulation for Central Sleep Apnea Introduction Pathophysiology Treatment Options for Central Sleep Apnea History of Phrenic Nerve Pacing A Transvenous Approach to Phrenic Nerve Stimulation: The Remedē System System Implantation Therapy Programming Transvenous Phrenic Nerve Stimulation Clinical Studies Feasibility Studies Pilot Study Remedē System Pivotal Trial Summary of Clinical Studies Conclusions Key Points Disclosures References 111 - Neurostimulation for Asthma Introduction Asthma: The Scope of the Problem Basic Science Clinical Results With Vagus Nerve Stimulation for Bronchoconstriction The Mechanism of Vagus Nerve Stimulation on Airway Reactivity Conclusion References 112 - Stimulation for Inspiration Background Current Experience Future Trends Conclusion Conflict of Interest Disclosure References 113 - Restoration of Cough via Functional Electrical Stimulation Current Techniques of Secretion Management Normal Cough Reflex Experimental Methods to Restore Cough Spinal Cord Stimulation (SCS) to Restore Cough, Animal Studies Spinal Cord Stimulation (SCS) to Restore Cough, Human Studies Electrical Stimulation System Implementation of the Cough Stimulator Following Surgical Implantation Results of Applied Electrical Stimulation Clinical Outcomes Long-Term Effects of Spinal Cord Stimulation (SCS) to Restore Cough Cost Benefit Analysis of Spinal Cord Stimulation (SCS) to Restore Cough Complications and Side Effects Future Directions Summary and Conclusions Acknowledgments Conflict of Interest Notification References XIII C - NEUROMODULATION FOR GASTROINTESTINAL DISORDERS INTRODUCTION 114 - Neural Control of the Gastrointestinal System Introduction Central Nervous System Control Extrinsic Control by the Autonomic Nervous System Intrinsic Gastrointestinal Control Though the Enteric Nervous System Gastrointestinal Reflexes Conclusion References Further Reading 115 - Spinal Cord Stimulation for Chronic Abdominal Pain Introduction Mechanisms of Abdominal Pain Causes of Chronic Non-Malignant Abdominal Pain Establishing a Diagnosis Spinal Cord Stimulation for Chronic Abdominal Pain Basic Science Clinical Evidence in Humans New Modalities of Spinal Cord and Dorsal Root Ganglia Stimulation for the Treatment of the Complexity of Chronic Abdominal Pain Conclusion References 116 - Emerging Gastric Stimulation for Dysmotility Disorder and Obesity Introduction Gastric Motility and Food Intake Gastric Myoelectrical Activity and Motility Roles of Gastric Motility in Food Intake and Digestion Methods of Gastric Electrical Stimulation Emerging Gastric Electrical Stimulation for Gastric Motility Disorders Gastric Pacing for Gastroparesis Dual-Pulse Gastric Electrical Stimulation for Gastroparesis Synchronized Gastric Electrical Stimulation Gastric Electrical Stimulation for Obesity Implantable Gastric Stimulation Tantalus Inhibitory Gastric Electrical Stimulation Summary References 117 - Intestinal Electrical Stimulation: Methodologies, Effects, Mechanisms, and Applications Introduction Physiology and Pathophysiology of Intestinal Motility Small Intestinal Motility Small Intestinal Myoelectrical Activity Intestinal Motility Disorders Methodologies Placement of Stimulation Electrodes Effects and Mechanisms on Intestinal Functions Effects of Intestinal Electrical Stimulation (IES) on Intestinal Slow Waves Effects on Intestinal Slow-Wave Dysrhythmia Effects and Mechanisms of Intestinal Electrical Stimulation (IES) on Intestinal Motility Effects and Mechanisms of Intestinal Electrical Stimulation (IES) on Intestinal Transit and Absorption Effects of Intestinal Electrical Stimulation (IES) on Other Organs Effects and Mechanism of Intestinal Electrical Stimulation (IES) on Glycemic Control Potential Applications Discussion and Conclusions References 118 - Neuromodulation for Nausea and Vomiting in Adult Patients Introduction Neurostimulation Gastroparesis Syndromes Clinical Benefits of Gastric Neuromodulation Therapy Additional Proposed Benefits New Developments for Gastroparesis and Gastroparetic Syndromes New Areas of Exploration of Neuromodulation Summary References Further Reading 119 - Neuromodulation for Gastrointestinal Dysmotility in Pediatric Patients Introduction Gastric Electrical Stimulation Sacral Nerve Stimulation Abdominal Transcutaneous Electrical Stimulation Future Directions Conclusion References 120 - Colonic Electrical Stimulation for Constipation Single-Channel Stimulation Multichannel Stimulation Mechanism of Action (MOA) Summary References XIII D - Neuromodulation for Urogenital Disorders INTRODUCTION Overview A Brief History of Neuromodulation in Urogenital Disorders Additional Applications for and Approaches to Neuromodulation for Urogenital Disorders Future Directions References 121 - Neurophysiology and Neuroanatomy of the Genitourinary Organs Introduction Peripheral Innervation of the Urogenital Organs Anatomy Physiology and Pharmacology of Efferent Pathways Lower Urinary Tract Genital Organs Physiology and Pharmacology of Afferent Pathways Lower Urinary Tract Genital Organs Anatomy of Central Nervous Pathways Controlling the Urogenital System Pathways in the Spinal Cord Afferent Projections in the Spinal Cord Efferent Neurons Spinal Interneurons Pathways in the Brain Central Neural Control of the Lower Urinary Tract Organization of Urine Storage Reflexes Sympathetic Storage Reflex Urethral Sphincter Storage Reflex Organization of Voiding Reflexes Spinobulbospinal Micturition Reflex Pathway Suprapontine Control of Micturition Spinal Micturition Reflex Pathway Neurotransmitters in Central Micturition Reflex Pathways Excitatory Neurotransmitters Inhibitory Neurotransmitters Neurotransmitters With Mixed Excitatory and Inhibitory Actions Central Neural Control of the Genital Organs Penile Erection Glandular Secretion Emission-Ejaculation Neurotransmitters in Central Sexual Reflex Pathways References 122 - Sacral Nerve Neuromodulation Introduction Mechanism of Action (MOA) Sacral Neuromodulation Procedure One-Stage Implantation Two-Stage Implantation Outcomes Complications Summary References 123 - Sacral Nerve Root Stimulation for Bladder Pain Syndrome/Interstitial Cystitis Background and Definitions Epidemiology of Bladder Pain Syndrome Etiology and Pathophysiology Diagnostic Evaluation Clinical Management of Bladder Pain Syndrome First Line: Conservative Therapies Second Line: Oral Therapies Second Line: Intravesical Therapies Third Line: Cystoscopic Techniques Fourth Line: Other Treatments Fifth Line: Open Surgery Sacral Nerve Stimulation Pelvic Neuroanatomy Historic Overview Rationale Behind Neuromodulation for Chronic Painful Conditions of the Pelvis and Painful Bladder Syndromes Indications and Contraindications for Sacral Nerve Root Stimulation Preoperative Assessment Techniques of Sacral Nerve Stimulation Sacral Transforaminal Approach The Retrograde (Cephalocaudal) Approach Anterograde (via Sacral Hiatus) Approach Retrograde Laminotomy Technique Programming Summary of Evidence of Efficacy and Complications Conclusion References Further Reading 124 - Restoration of Bladder and Bowel Control After Spinal Cord Injury History of the Topic History of the Problem History of Current Solutions Review of the Current Knowledge Base of the Topic Clinical Effects Single-Center Results Multicenter Results Reliability Quality of Life, Cost-Effectiveness, and Economic Consequences Safety and Efficacy Data in the United States Discussion of Future Trends and Pathways to Expanding the Knowledge Base References XIV - Neuromodulation for Endocrine, Immune, and Inflammatory Disorders INTRODUCTION Neuromodulation for Inflammatory Diseases Neuromodulation to Regulate Hemostasis Neuromodulation for Inflammatory Bowel Disease Neuromodulation for Diabetes Neuromodulation to Regulate Pain Neuromodulation to Regulate Diseases of the Heart Decoding Neural Signals for Closed-Loop Neuromodulation and Advanced Diagnostics Closing Remarks 125 - Vagus Nerve Stimulation and Regulation of Inflammation Therapeutic Challenges in Inflammatory Disease The Nervous System is an Integral Part of the Immune System The Inflammatory Reflex The Inflammatory Reflex in Experimental Disease Vagus Nerve Stimulation in Experimental and Clinical Disease Bioelectronic Medicine Conclusions References 126 - Activation of the Inflammatory Reflex in Rheumatoid Arthritis and Inflammatory Bowel Disease; Preclinical Evidence Introduction Structure and Function of the Cholinergic Antiinflammatory Pathway Preclinical Evidence for Cholinergic Antiinflammatory Pathway Effect in Models of Rheumatoid Arthritis Preclinical Evidence for Cholinergic Antiinflammatory Pathway Effect in Models of Inflammatory Bowel Disease Summary References 127 - Bioelectronic Therapy for the Treatment of Rheumatoid Arthritis and Inflammatory Bowel Disease Introduction The First Clinical Study of Vagus Nerve Stimulation in Patients With Rheumatoid Arthritis The First Clinical Studies of Vagus Nerve Stimulation in Patients With Inflammatory Bowel Disease Summary of Clinical Safety Data Development of an Application-Specific Investigational VNS System for RA and IBD Future Directions: Toward a Universally Implantable and Closed-Loop Device Platform Summary References 128 - Vagal Nerve Stimulation Versus Sacral Nerve Stimulation for Control of Inflammation Introduction Cholinergic Antiinflammatory Pathway Vagal Nerve Stimulation for Intestinal Inflammation Vagal Nerve Stimulation in Animal Models of Inflammatory Bowel Disease Vagal Nerve Stimulation for Inflammatory Bowel Disease Potential of Noninvasive Vagal Nerve Stimulation for Inflammatory Bowel Disease Sacral Nerve Stimulation for Intestinal Inflammation Sacral Nerve Stimulation for Proctitis Sacral Nerve Stimulation for Intestinal Inflammation Possible Antiinflammatory Pathway of Sacral Nerve Stimulation References Further Reading 129 - Neuromodulation Therapies for Cardiac Disease Introduction Vagus Nerve Stimulation Stimulation Method Neuromodulation Mechanism of Vagus Nerve Stimulation Vagus Nerve Stimulation and Heart Failure Vagus Nerve Stimulation and Myocardial Infarction Vagus Nerve Stimulation and Arrhythmias Spinal Cord Stimulation Stimulation Method Neuromodulation Mechanism of Spinal Cord Stimulation Spinal Cord Stimulation and Refractory Angina Pectoris Spinal Cord Stimulation and Heart Failure Spinal Cord Stimulation and Myocardial Infarction Spinal Cord Stimulation and Arrhythmia Carotid Body Ablation and Neuromodulation Method of Carotid Body Ablation Neuromodulation Mechanism of Carotid Body Ablation Baroreceptor Stimulation Stimulation Method Neuromodulation Mechanism of Baroreceptor Stimulation Renal Denervation Method of Denervation Neuromodulation Mechanism of Renal Denervation Autonomic Regulation Therapy: Cardiac Afferent Targets Conclusion References Further Reading 130 - The Neural Tourniquet Introduction The Inflammatory Reflex Traumatic Hemorrhage Bleeding in Clinical Medicine The Neural Tourniquet Swine Ear Hemorrhage Rodent Liver Hemorrhage Murine Tail Hemorrhage Murine Hemophilia A Clinical Applications Conclusions References 131 - Sensing and Decoding Neural Signals for Closed-Loop Neuromodulation and Advanced Diagnostics in Chronic Disease and Injury Introduction Sensing, Neural Decoding, and Closed-Loop Neuromodulation Neuroimaging Techniques for Advanced Diagnostics Minimally Invasive Neurosensing Techniques for Advanced Diagnostics Invasive Neurosensing Methods for Advanced Diagnostics Conclusion References Further Reading 132 - The Role of Vagus Nerve Stimulation in the Treatment of Central and Peripheral Pain Disorders and Related Comorbid Somatoform Conditions History and Background of Vagus Nerve Stimulation (VNS) Neuroanatomy of the Vagus Nerve and Selective Activation by Vagus Nerve Stimulation Evidence of Neurotransmitter Modulation The Noradrenergic and Cholinergic Antiinflammatory Pathways, Linking the Autonomic Nervous System With Inflammation Central Sensitization Through Persistent, Peripheral, Pain Activation, and Inflammation The Comorbidity of Pain and Somatoform Disorders Vagus Nerve Stimulation Opposes the Feed-Forward Loop of Inflammation, Neurotransmitter Imbalance, and Neuronal Hyperexcitabilit... Clinical Evidence of Vagus Nerve Stimulation for the Treatment of Central and Peripheral Pain Disorders and Their Somatoform Com... Conclusion References 133 - Insulin Resistance, Glucose Metabolism, Inflammation, and the Role of Neuromodulation as a Therapy for Type-2 Diabetes Overview Background The Role of Inflammation in Insulin Resistance Inflammatory Cytokines Inhibit the Production of Glycogen Key Antiinflammatory Pathways and Their Roles in Glucose Homeostasis Acetylcholine Blocks Hepatic Glucose Output and Enhances Glycogen Synthetase Vagus Nerve Stimulation Blocks Inflammatory Pathways Possible Relevance of Innervation of the White Adipose Tissue Clinical Evidence of VNS Reducing Insulin Resistance in Humans Conclusion References XV - Noninvasive Neuromodulation INTRODUCTION References 134 - Transcranial Magnetic Stimulation Brief Introduction Basic Mechanisms of TMS and TMS as a Tool to Investigate Human Brain Cortex Physiology Distance Between the Coil and the Cortex Coil Orientation and Shape Transcranial Magnetic Stimulation to Probe Cortical Excitability, Inhibitory, and Facilitatory Mechanisms Single Pulse Transcranial Magnetic Stimulation Cortical Silent Period Paired Pulse Intracortical Facilitation Short Intracortical Facilitation Long Interval Intracortical Inhibition Paired Pulse to Probe Interhemispheric, Cerebellar, and Afferent Inhibition Transcranial Magnetic Stimulation to Change Brain Activity Traditional Repetitive Transcranial Magnetic Stimulation Patterned Repetitive Transcranial Magnetic Stimulation Paired Associative Stimulation Clinical Applications of Repetitive Transcranial Magnetic Stimulation Depression Pain Stroke Safety of Transcranial Magnetic Stimulation Conclusions Acknowledgments References 135 - Transcranial Direct Current Stimulation (tDCS) Introduction Historical Background and Other Transcranial Electrical Stimulation Approaches Developments From Electrosleep to Cranial Electrotherapy Stimulation Developments From Electroanesthesia to Limoge Current and Other Related Methods Development of Direct Current Stimulation Transcranial Direct Current Stimulation Customization Transcranial Direct Current Stimulation Terminology Transcranial Electrical Stimulation and Transcrianial Direct Current Stimulation “Dosage” Origins of Specificity During Transcranial Direct Current Stimulation: Anatomical, Activity-Selective, and Input-Bias Mechanisms... Anatomical Transcranial Direct Current Stimulation Specificity and the “Sliding-Scale” Model Activity-Selectivity and Task-Specific Modulation Input-Selectivity and Bias Preparation for Transcranial Direct Current Stimulation Stimulation Selecting and Preparing Electrodes and Contact Medium Selecting and Preparing Electrode Placement Computational Models of Transcranial Direct Current Stimulation for Electrode Placement Common Montages Methods for the Generation and Use of Computational Forward Models of Transcranial Direct Current Stimulation Safety Considerations for Transcranial Direct Current Stimulation Transcranial Direct Current Stimulation Safety Data From Human Trials and Models Efficacy References 136 - Transcranial Alternating Current Stimulation and Transcranial Random Noise Stimulation Introduction Transcranial Alternating Current Stimulation Studies With Animals Mechanism of Action The Effects of Transcranial Alternating Current Stimulation on Cognition Random Noise Stimulation A Special Case of Transcranial Random Noise Stimulation: Transcranial Pulsed Current Stimulation Mechanism of Action The Effects of Random Noise Stimulation on Cognition Clinical Effects of Alternating (tACS) and Random Noise (tRNS) Stimulation Conclusions References 137 - Novel Methods of Transcranial Stimulation: Electrosonic Stimulation Introduction Noninvasive Electromagnetic Methods Transcranial Magnetic Stimulation Transcranial Direct Current Stimulation Nonelectromagnetic Techniques Acoustic Stimulation Electrosonic Stimulation Conclusions Acknowledgments References 138 - Optimization of Noninvasive Brain Stimulation Clinical Trials Introduction How to Stimulate Stimulation Parameters Where to Stimulate Brain Region Targets of Interest When to Stimulate Timing of Stimulation Patient Selection Considerations Combinations of Therapies Summary of Clinical Effects Repetitive Transcranial Magnetic Stimulation Transcranial Direct Current Stimulation The Future of NIBS References 139 - Transcranial Direct Current Stimulation for Fatigue and Attentional Disorders Introduction Medical Causes of Fatigue and Chronic Fatigue Syndrome Nonmedical Sources of Fatigue Transcranial Direct Current Stimulation as a Countermeasure for Fatigue Attention and Vigilance Transcranial Direct Current Stimulation’s Effects on Attention and Vigilance References XVI - THE BUSINESS END OF NEUROMODULATION INTRODUCTION 140 - Perspectives on the Issues and Barriers to Starting a New Neuromodulation Company From New Start-Ups in Neuromodulation Introduction My Perspectives on Starting a New Start-Up in Neuromodulation Industry Challenges: Perspectives on Starting a Neuromodulation Start-Up Company Starting a Neuromodulation Company and Bringing It to Fruition Launching a Start-Up An Idea Unmet Needs and Validated Market Compelling Financials Scientific Foundation Clinical Data and Intellectual Property Team Lessons Learned Moving Experience to Developing a New Platform for Neuromodulation Step One: Grounded Engineering and Entrepreneurship Background; a Bit of My History Step Two: A Technology Is Born Step Three: Neuromodulation Miniaturization for Pain Relief Step Four: Technology Hurdles Step Five: Lifelong Regulatory Compliance and Clinical Evidence Step Six: Market Awareness and Distribution of the Minimally Invasive Solution 141 - The Birth of an Industry Early Neuromodulation Devices The 21st Century Neuromodulation Industry 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Competitive Landscape Future Outlook References 142 - Neuromodulation: Regulatory Considerations Brief History of Medical Device Regulation Time and Cost of Device Development Investigational Device Exemption (IDE) Determining Whether an Investigational Device Exemption (IDE) Is Needed Investigational Device Exemption (IDE)-Exempt Studies Nonsignificant Risk Studies Implant Serious Risk to Health Supporting or Sustaining Human Life Early Feasibility Investigational Device Exemption The Case for an Investigational Device Exemption Device Classification FDA’s Classification Process Classification of Neuromodulation Devices Market Approval for Neuromodulation Systems Premarket Application (PMA) Traditional 510(k) De Novo 510(k) Humanitarian Device Exemption (HDE) Innovation Pathway and Expedited Access Pathway Postmarket Regulation of Neuromodulation Devices Conclusions References 143 - Reimbursement for Neuromodulation Therapies and Technologies Introduction Reimbursement Structure for Neuromodulation Therapies and Technology in the U