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 VIII A - Spinal Cord Stimulation for Pain Control INTRODUCTION References 43 - Physiology and Pathophysiology of Chronic Pain Physiology and Pathophysiology of Chronic Pain Physiology and Pathophysiology of Chronic Pain Physiology and Pathophysiology of Chronic Pain Pain Pathogenesis Nociceptors Peripheral Mechanisms of Chronic Pain Nerve, Root, and Spinal Mechanisms Spinal and Subcortical Pain Signaling Cortical and Subcortical Signaling Conclusion References 44 - Management Strategies for Chronic Pain Introduction Evaluation of the Patient With Chronic Pain Management of the Patient With Chronic Pain Pharmacological Modalities Acetaminophen/Nonsteroidal Antiinflammatory Drugs Anticonvulsants/Antidepressants Opioids Interventional Pain Medicine Pain Psychology and Complementary Medicine Neuromodulation Medical Considerations for Neuromodulation Conclusion References Further Reading 45 - History of Spinal Cord Stimulation Surgical Procedures for Pain Control Historical Uses of Electrical Stimulation The Gate-Control Theory of Pain Peripheral Nerve Stimulation Dorsal Column Stimulation Early Devices General Clinical Application Screening Methods Device Manufacturers Scientific Progress Technical Progress “Totally Implantable” Systems Rechargeable Systems Paresthesia Mapping Reimbursement Refinement of Selection Criteria New Technology Conclusions Acknowledgments References 46 - Functional Magnetic Resonance Imaging in the Neuromodulation of Pain Introduction Functional Imaging Modalities Functional Magnetic Resonance Imaging Spinal Cord Stimulation Arterial Spin Labeling Magnetic Resonance Tractography Clinical Applications Chronic Low Back Pain Trigeminal Neuralgia Conclusion References 47 - The Development of Algorithms for Pain Care Including Neuromodulation Therapies: Introducing the SAFE Principles Introduction Prior Algorithms to Chronic Pain Treatment The SAFE Principles Safety Appropriateness Time to Fiscal Neutrality Efficacy Summary Conclusion References 48 - Neurostimulation for the Treatment of Complex Regional Pain Syndrome Introduction Spinal Cord Stimulation Efficacy in Treating CRPS Benefits and Risks of Spinal Cord Stimulation The Role of SCS in the Comprehensive Interdisciplinary Treatment Model of CRPS Patient Selection and the Screening Trial Patient Management Cost Effectiveness Dorsal Root Ganglion Stimulation Peripheral Nerve Stimulation References 49 - Spinal Cord Stimulation for Peripheral Neuropathic Pain Overview History and Mechanisms of Action of Spinal Cord Stimulation Peripheral Neuropathic Pain and Conventional Spinal Cord Stimulation General Recommendations Neuroanatomic Location Roots Failed Back Surgery Syndrome Postherpetic Neuralgia Neuroanatomic Location Plexus Plexopathy (Traumatic) Neuroanatomical Location: Peripheral Nerve Painful Diabetic Polyneuropathy Complex Regional Pain Syndrome Phantom Limb Pain Current Research and Future Directions (Possible) Indicators for Better Outcome Timing Allodynia Other Techniques Beyond Conventional Neuromodulation Future Directions References 50 - Spinal Cord Stimulation for the Treatment of Low Back Pain Introduction Spinal Cord Stimulation Without Paresthesia Other Stimulation Targets for Low Back Pain Comparative Efficacy Studies and the Role of Spinal Cord Stimulation Neuropathic Low Back Pain Conclusion References 51 - Complications of Spinal Cord Stimulation Introduction Background Overview of Complications Identification and Management of Complications Patient Selection Postoperative Complications Complications Related to Hardware Lead Migration and Fracture Pain From Implanted Hardware Complications Related to Biological Causes Infection and Hypersensitivity Reactions Postoperative Noninfectious Fluid Collection Traumatic Injury Tolerance Conclusion References 52 - Clinical Aspects of Burst Stimulation for Pain Control Introduction Introducing Burst Stimulation A Hypothesis on the Mechanisms of Action Clinical Outcomes of Burst Stimulation Pain Reduction and Further Improvement of Pain Reduction Recapturing Pain Paresthesia Patient Preference Other Outcomes and Adverse Events Cost Effectiveness of Burst Stimulation Future Directions Conclusion Disclosure References Further Reading 53 - Dorsal Root Ganglion Stimulation for Pain Control Dorsal Root Ganglion Stimulation: The Intervention The DRG’s Role in Pain DRG Stimulation Implantation: Surgical Considerations Preimplantation Planning Lead Implantation Securing the Leads Trial Period Options INS Placement Programming Follow-up Outcomes The European Experience The Australian Experience Worldwide Experience Conclusions Acknowledgments Conflict of Interest Statement References 54 - Ten Kilohertz (10kHz) High-Frequency Spinal Cord Stimulation Introduction Clinical Data Chronic Back and Leg Pain Upper-Extremity and Neck Pain Peripheral Neuropathy Clinical Outcomes of SCS Using Other Higher Frequencies Safety Patient Selection: Psychological Evaluation for Implantable Devices Implantation Technique Discussion and Conclusions References 55 - A Review of Spinal Cord Stimulation Cost Studies Introduction General Considerations About Spinal Cord Stimulation Cost Studies Ways to Study Cost Review of Cost Studies Cost Studies Based on Technology or Treatment Choices First SCS Cost Study Compared Pre/PostSCS Healthcare Use Outpatient Percutaneous Electrodes Versus Inpatient Paddles Inpatient SCS Cost Impact of the Treatment Continuum on PostSCS Healthcare Costs Technological Improvements and Cost of SCS Modeling Cost Impact of Rechargeable Batteries Modeling High-Frequency SCS Costs in Patients With FBSS Impact of Complications Complications and Costs of Percutaneous Versus Paddle Electrodes Retrospective Analysis of the Cost of Complications Studies in Failed Back Surgery Syndrome/Low Back Pain First Full Report on Cost of SCS Health Technology Assessment From WHO SCS Versus “Chronic Maintenance” Snapshot of Cost and Effectiveness of SCS for FBSS in One Practice Patients Serving as Their Own Controls Reveal SCS Payback Date Long-Term Costs in FBSS Patients Who Passed Versus Those Who Failed an SCS Screening Trial Long-Term Prospective Multisite Cost-Effectiveness Analysis Use of Models for Analyzing the Cost Effectiveness and Cost Utility of SCS in FBSS Patients Three-Way Analysis of Long-Term Cost Utility and Cost Effectiveness From a Cross-Over RCT of SCS Versus Reoperation for FBSS Six-Month Comparison of Healthcare Costs, Health Resources Use, and QOL in FBSS: Predictable Results, Interesting Problems Cost Study Based on a Criticized Clinical Study Modeling Costs of Three Treatments for FBSS Real-World 24-Month Cost-Effectiveness and Cost-Utility Analysis Modeling Cost Utility of SCS Versus Reoperation for FBSS in Colombia Studies in Ischemic Pain Cost–Utility Analysis for SCS Used to Treat Angina Another Early Indication That SCS is Cost Effective in Angina Reduction of Hospitalizations in Angina Patients Treated With SCS Patients Serving as Their Own Controls Reveal the SCS Payback Date Immediate Cost Savings With SCS Versus Bypass Surgery Second Cost–Utility Analysis in Angina Patients Retrospective Cost–Benefit Study in Angina Patients Cost Effectiveness of SCS Versus Percutaneous Myocardial Laser Revascularization Comparison of Costs and Outcomes Between SCS and Enhanced External Counterpulsation Problems With Patient Selection, Techniques, and Equipment Cast Doubt on Cost and Effectiveness Conclusions of an RCT in Patient... Cost Description in Patients With Renal Failure and Ischemia Studies in Chronic Regional Pain Syndrome Studies Relying on a Randomized Comparison of SCS Plus Physical Therapy Versus Physical Therapy Alone Prospective CRPS Cost Study Study in Spasticity Single Study of the Cost of SCS in Spasticity Omits Details Mixed Indications Retrospective Cost–Benefit Analysis of Two Neurostimulation Techniques for Several Indications Study Models SCS Cost Effectiveness in Four Indications Cost of SCS in Neuropathic Pain and Angina Impact of SCS Treatment on Healthcare Budgets Reviews of the SCS Cost Literature: It Is a Fool’s Errand to Review Reviews First SCS Cost Literature Review Another Look at CRPS Review Focusing on FBSS Health Technology Assessment of SCS for Ischemic or Neuropathic Pain Reimbursement National Effort to Link SCS Reimbursement With Continuous Quality Improvement Differential Effect of Two Types of Reimbursement on SCS Outcomes How Can the Cost Effectiveness of SCS Be Optimized Appropriate Patient Selection Appropriate Techniques Improving Equipment Additional Considerations Position of SCS on Treatment Algorithms Cost Impact of Conducting a Screening Trial Conclusions References Further Reading VIII B - Peripheral Nerve Stimulation for Pain Control INTRODUCTION References 56 - Anatomy and Physiology Related to Peripheral Nerve Stimulation Nerve Trunks Fascicular Anatomy Blood Supply of Peripheral Nerves Neural Electrode Interface Conclusion References 57 - Peripheral Nerve Stimulation for Pain Suppression Introduction Multiple Theories Exist as to the Exact Mechanism/s Through Which PNS Achieves Pain Relief PNS Has a Long History of Success, But Existing Technology and Early Methods of Implantation Previously Required Precise Neurosu... Leads Initially Designed for Spinal Cord Stimulation Have Been Used for PNS, But Studies Indicated That Technology Designed Spec... New Technique Introduced to Overcome Barriers to PNS Peripheral Field Stimulation Ultrasound Guidance Improves Outcomes Recent FDA Clearance of Next-Generation PNS Systems May Enable the Potential of PNS Documented in Research Studies to Be Transla... StimQ PNS System Has Received FDA Clearance StimRouterTM Neuromodulation System Has Received FDA Clearance SPRINT® PNS System Has Received FDA Clearance Other Investigational PNS Systems Are in Development Conclusion Disclosures References 58 - Peripheral Nerve Stimulation for Facial Pain Introduction Mechanism of Action of Peripheral Nerve Stimulation Patient Selection for Peripheral Nerve Stimulation Efficacy of Peripheral Nerve Stimulation for Facial Pain Electrical Stimulation of Infraorbital and Supraorbital Nerves Trigeminal Branch Stimulation Electrical Stimulation of Auriculotemporal Nerve Combination Neuromodulation Therapies Adverse Events and Serious Adverse Events Summary References 59 - Combined Spinal Cord Stimulation and Peripheral Nerve Field Stimulation for the Treatment of Chronic Back and Neck Pain Introduction Combined SCS and PNFS for Low Back Pain Combined SCS and PNFS for Neck Pain Adverse Events Programming Advantages of Combination Therapy Summary References 60 - Percutaneous Peripheral Nerve Stimulation for the Management of Postoperative Pain Existing Treatments for Postoperative Pain History: Treating Postoperative Pain With Electrical Stimulation Percutaneous Peripheral Nerve Stimulation for Postoperative Pain Ultrasound Guidance for Percutaneous Lead Insertion Open-Coil Lead: Design and Safety Profile Stimulation Paradigm Clinical Studies of Percutaneous PNS for Postoperative Pain Future Directions Acknowledgments References 61 - Peripheral Nerve Field Stimulation for Intractable Pain Introduction Mechanisms of Action Equipment Technique Indications Using Two Different Systems at the Same Time PNfS and TENS Can PNfS Be Used to Treat Nociceptive Pain Complications Results Conclusions References Further Reading 62 - Occipital Nerve Stimulation for Treatment of Intractable Headache Syndromes Introduction Medical Treatment of Headache Disorders Neurosurgical Diagnosis and Management of Occipital Pain Neurology and Chronic Headaches Neuromodulation Occipital Nerve Anatomy ONS Implant Technique Intraoperative Stimulation Testing Electrode Fixation and Tunneling Implantable Pulse Generator Implantation Summary of Technique Elements Results ONSTIM 2010 Study (Medtronic Inc.) St. Jude (2012) PRISM 2009 (Boston Scientific) Complications Mechanisms of Action Disruptive Innovations Conclusions References 63 - Neuromodulation for Headaches—Sphenopalatine Ganglion Stimulation Introduction Diagnostic Criteria of the Primary Headache Disorders Targeted With SPG Inhibition SPG Anatomy and Headache Pathophysiology Brief History of the Role of SPG Modulation in Headache Treatment Randomized Controlled Trial Summary of the Safety and Efficacy Data Acute Efficacy From the RCT Preventive Efficacy From the RCT Overall Efficacy Responses From the RCT Open-Label Efficacy Data Registry and Safety Data Proof of Concept of SPG Neuromodulation in Cluster Headache The Future Conclusions References VIII C - Intrathecal Therapies for Pain Control and the Control of Spasticity INTRODUCTION Reference 64 - Relevant Anatomy for Spinal Drug Delivery Introduction Relevant Anatomy Spinal Cord Nerve Root Vertebral Column Ligaments of the Spine Blood Supply to the Spinal Cord Spinal Cord Venous System The Epidural Space The Vacuum Effect Anatomical Issues and Considerations Innervation of the Spinal Dura Cerebral Spinal Fluid Dynamics, Flow, Production, Volume, and Overview Nerve Root Size and Volume Spinal Tracts Surgical Techniques Spinal Drug Delivery Positioning of Patients for Intrathecal Drug Delivery Systems Fluoroscopic Imaging Needle Placement Catheter Placement Needle Removal Epidural Placement Radiological Confirmation of Catheter Placement Distribution of Agents Conclusion References 65 - Evolution of the Spinal Delivery of Opiate Analgesics Introduction Neuraxial Drugs: The First 20Years Delivery System Drugs Spinal Anesthesia Neuraxial Morphine Neuraxial Opiates: The Last 40Years Preclinical Studies on the Analgesic Actions of Neuraxial Opiates Early Clinical Studies on the Analgesic Actions of Neuraxial Opiates Discovery of the Underlying MOA for Spinal Opiate Actions Identification of Subtypes of Opioid Receptors: Mu, Delta, Kappa Development of Catheter-Based Infusion Techniques Evolution of the Neuraxial Delivery of Targeted Therapeutics Epidural Versus Intrathecal Delivery Intrathecal Pharmacokinetics Other Intrathecal Analgesics Opioids Nonopioid Agents Developing Concerns Over Spinal Drug Safety Side-Effects of IT Administration of Opiates Effects on Physiological Functions Hyperalgesia Clonus Tolerance Granuloma Concluding Commentary References 66 - Pharmacology of Intrathecal Therapy Introduction Indications Pharmacokinetics and Pharmacodynamics Opioids Local Anesthetics Ziconotide Clonidine CSF and Catheter Placement Agent Selection Morphine Ziconotide Fentanyl Hydromorphone Bupivacaine Clonidine Future Therapy Summary References Further Reading 67 - Cerebrospinal Fluid Dynamics and Intrathecal Delivery Introduction Understanding Dynamic CSF Flow Introduction to Pulsatile CSF Dynamics and CSF–Parenchyma–Vasculature Coupling Respiratory Influence on CSF Flow Geometry-Induced Flow Phenomena (Nerve Roots and Trabeculae) Cilia-Induced CSF Flow in the Cerebral Ventricles Acquisition of CNS Anatomy CSF Flow Measurements PC MRI Four-Dimensional MRI Current Developments CSF Production and Reabsorption Classical Hypothesis The New Hypothesis of CSF Production and Reabsorption in the Brain Osmotic Gradient-Driven Flow The Role of Perivascular Spaces on Tracer Transport Intrathecal Drug Transport and Delivery Intrathecal Administration Therapy Cerebrospinal Fluid Pulsation Infusion Type: Bolus Versus Drug Pump Impact of Drug Chemistry on Pharmacokinetics In Vitro and Mathematical Models for Predicting IT Drug Dispersion In Vitro Models of the CNS In Silico Models of IT Delivery Nanoparticles for Magnetically Guided Therapies Modeling Limitations of the Perivascular Space Design of Optimal Therapies for Intrathecal Administration Future Directions and Open Questions Open Issues References 68 - Exploring Nonopioid Analgesic Agents for Intrathecal Use Introduction Adenosine Mechanism of Action Clinical Evidence Closing Remarks Resiniferatoxin Mechanism of Action Clinical Evidence Closing Remarks Oxytocin Mechanism of Action Clinical Evidence Closing Remarks Midazolam Mechanism of Action Clinical Evidence Closing Remarks Gabapentin Mechanism of Action Clinical Evidence Closing Remarks Neostigmine Mechanism of Action Clinical Evidence Closing Remarks Conclusion References Further Reading 69 - Potent Neurotoxins for Cancer Pain Treatment: Resiniferatoxin and Saporin Introduction Resiniferatoxin History Mechanism of Action Preclinical Data Resiniferatoxin and Cancer Pain Future Directions for Resiniferatoxin Saporin History Pathophysiology Safety and Efficacy of Saporin Substance-P–Saporin and Cancer Pain The Future for Substance-P–Saporin Conclusion References 70 - The Development of Guidelines for Intrathecal Therapies for Pain Control. History and Present Guidelines Introduction PACC 2000 PACC 2003 PACC 2007 PACC 2012 PACC 2016 Conclusion References 71 - Compounding for Intrathecal Analgesic Agents Introduction What Is Compounding Standards for Compounding Regulatory Considerations Regulatory Issues—State Regulatory Issues—Federal Avoidable Errors and Their Tragic Consequences Standards Facility Standards Equipment Standards Cleaning and Disinfection of the Sterile Compounding Facility Personnel Training and Testing Gowning Fingertip Assessments Environmental Monitoring Surface Sampling The Compounding Process Filtration Endotoxins Stability Considerations Provider Liability Conclusion References 72 - Intrathecal Baclofen Therapy for the Control of Spasticity Introduction Patient Selection Patient Selection for IBT IBT Trialing Therapy Initiation Therapy Maintenance Summary References VIII D - INTRACRANIAL PROCEDURES FOR CHRONIC PAIN INTRODUCTION 73 - Deep Brain Stimulation for Pain Relevant History of the Topic Including Developments Over the Past Decade Review of the Current Knowledge Base of the Topic Summary of the Safety and Efficacy Data Discussion of Future Trends and Pathways to Expanding the Knowledge Base Dual Target Stimulation Understanding the Insertional Effect Modulation of the Affective Component of Pain References IX - NEUROMODULATION FOR MOVEMENT DISORDERS INTRODUCTION 74 - Deep Brain Stimulation in Parkinson’s Disease Introduction Deep Brain Stimulation in Parkinson’s Disease Selection Criteria for DBS in PD Target Selection and Surgical Technique Treatment Planning: Indirect and Direct Targeting Surgical Procedure: Awake and Asleep DBS Postoperative Complications Deep Brain Stimulation Programming in Parkinson’s Disease Side-Effects of Deep Brain Stimulation Conclusion References 75 - Deep Brain Stimulation for Tremor Historical Perspective Pertinent Anatomy, Physiology, and Disease Pathophysiology Rationale for Neuromodulation, Target Selection, and Approach Indications and Patient Selection Criteria Implant Procedure Details Programming and Other Points of Consideration Most Recent Literature Complications and Avoidance What the Future Holds (Next 5Years) Conclusions References 76 - Deep Brain Stimulation for Dystonia Introduction Diagnosis and Classification of Dystonia Medical Therapy for Dystonia Surgical Therapy for Dystonia The DBS Procedure Patient Selection Surgical Procedure Stereotactic Technique Anatomical Targeting Microelectrode Recording DBS Surgery in Children Macroelectrode Stimulation Implantation of the Pulse Generator Programming the Device Clinical Results Indicators of DBS Response Stimulation Frequency Longevity of Response Pallidal DBS in Cervical Dystonia Pallidal DBS for Primary Cranial–Cervical Dystonia (Meige Syndrome) Pallidal DBS for Secondary Dystonia Complications of DBS Therapy Alternative Targets for Deep Brain Stimulation in Dystonia Conclusions Acknowledgment References 77 - Deep Brain Stimulation in Tourette Syndrome Introduction Diagnosis and Prevalence Treatment of Tourette Syndrome Surgical Treatment of Tourette Syndrome Historical Perspective Deep Brain Stimulation Selection Criteria and Surgical Evaluation Inclusion Criteria Exclusion Criteria Surgical Procedure and Perioperative Management Stimulation Parameters Present and Future Perspectives References 78 - Surgical Management of Hemifacial Spasm and Meige Syndrome Hemifacial Spasm Introduction Etiology and Pathophysiology Clinical Manifestations Diagnosis Clinical Diagnosis Neuroradiologic Evaluations Additional Methods Management Medical Treatment Microvascular Decompression Operative Technique Patient Positioning Scalp Incision to Craniectomy Dural Incision and Exposure Decompression of the Offending Vessel Closure Intraoperative Monitoring Surgical Outcome Complications Conclusions Meige Syndrome Introduction Clinical Manifestations and Pathophysiology Management Operative Techniques of Globus Pallidus Interna Deep Brain Stimulation Outcome and Complications Conclusions References 79 - Deep Brain Stimulation of the Pedunculopontine Tegmental Nucleus Improves Static Balance in Parkinson’s Disease Introduction Methods and Materials Patients Stabilometry and Postural Instability Statistics Results Discussion Highlights Acknowledgments References 80 - Infusion Therapy for Movement Disorders Review of the Current Knowledge Base of the Topic GDNF and NTN Preclinical Studies of GDNF and NTN Delivery for PD Intraventricular Administration of GDNF and NTN in Rodents Intraventricular Administration of GDNF and NTN in Nonhuman Primates Clinical Trials of Intraventricular Infusion of GDNF for PD Localized Intraparenchymal Delivery of GDNF in Rodents Intraputamenal Delivery of GDNF and NTN in Nonhuman Primate Studies Chronic Intraputamenal Infusion of GDNF and Related Toxicity Clinical Trials of Intraputamenal Delivery of GDNF A Multicenter Randomized Controlled Trial of Intraputamenal GDNF Infusion for PD Clinical Trials of Intraputamenal AAV-NTN Gene Therapy Convection-Enhanced Delivery of GDNF to the Brain The Rationale for Chronic Intermittent CED Alternative Neurotrophins—The CDNF/MANF Family Reference Further Reading X - Neurostimulation for Epilepsy INTRODUCTION References 81 - Epilepsy: Anatomy, Physiology, Pathophysiology, and Disorders Introduction Diagnosis of Epilepsy Pathophysiology Pathophysiology of Temporal Lobe Epilepsy Prognosis—Drug-Resistant Epilepsy Neurostimulation for the Control of Seizures in Humans References Further Reading 82 - Vagal Nerve Simulation NCP Device Components Theoretical Basis of VNS Clinical Utility of VNS Efficacy Use in Children Cost Analysis Advantages of VNS Patient Satisfaction Patient Selection Alternative Uses of VNS Operative Procedure General Considerations Relevant Anatomy Operative Procedure in Detail Lead Removal or Revision Complications and Adverse Events References Further Reading 83 - Deep Brain Stimulation for Epilepsy Introduction Limbic Network as Conduit of Seizure Propagation Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Rationale Trials Before SANTE The SANTE Trial The Problem of Anatomical Localization Deep Brain Stimulation of the Hippocampus Rationale Clinical Evidence Problem of Memory Impairment Future Directions Deep Brain Stimulation Side-Effects and Complications Conclusions References Further Reading 84 - Closed-Loop Responsive Stimulation for Epilepsy Introduction The Burden of Epilepsy A History of Stimulation Closed Loop Neurostimulation The Pivotal Trial Long-Term Results Mechanisms of Action The Responsive Neurostimulator System Responsive Neurostimulator System Candidates Device Description Surgical Technique System Features Future Directions Conclusion References Further Reading XI - NEUROMODULATION FOR BEHAVIORAL AND COGNITIVE DISORDERS INTRODUCTION 85 - Deep Brain Stimulation for Obsessive–Compulsive Disorder Introduction Pathophysiology of Obsessive–Compulsive Disorder Deep Brain Stimulation for Obsessive–Compulsive Disorder Anterior Limb of Internal Capsule Ventral Capsule and Ventral Striatum Nucleus Accumbens Subthalamic Nucleus Inferior Thalamic Peduncle Other Targets Patient Selection, Team Approach, and Ethical Considerations Surgical Techniques of Deep Brain Stimulation Implantation Conclusion References 86 - High-Intensity Focused Ultrasound Surgery for the Treatment of Obsessive–Compulsive Disorder Introduction Neural Circuitry of Obsessive–Compulsive Disorder History of High-Intensity Focused Ultrasound Principles of Transcranial Magnetic-Resonance-Guided Focused Ultrasound Surgery High-Intensity Focused Ultrasound Magnetic-Resonance-Guided Focused Ultrasound Surgery Bilateral Thermal Capsulotomy With MRgFUS as a Treatment for Obsessive–Compulsive Disorder Patient Selection Surgical Procedures Follow-Up Examination and Clinical Evaluations Clinical Results of the Bilateral Thermal Capsulotomy Using MRgFUS Clinical Outcomes Adverse Events Controversial Issues Skull-Related Factors: Skull Density Ratio and Skull Volume MR-Induced Vertigo Limitation of the Treatment Area According to the Transducer Frequency Conclusions References 87 - Deep Brain Stimulation for Highly Refractory Depression Introduction Treatment of Depression Pharmacotherapies Treatment of Refractory Patients Brain Stimulation Techniques Development of DBS in Neuropsychiatry History Affect and Mood Effects Observed During Depth Electrode Stimulation DBS for Obsessive–Compulsive Disorder Technical Aspects of DBS Implantation Stimulation Technique Customizing Therapy DBS for Primarily Depressive Illness Stimulation Targets for Depression Subgenual Cingulate Cortex Ventral Capsule/Ventral Striatum Nucleus Accumbens Superolateral Branch of the Medial Forebrain Bundle Lateral Habenula Inferior Thalamic Peduncle Issues Independent of DBS Target Do Early Effects of Stimulation Have Prognostic Value Mechanism(s) of Action of DBS Adverse Effects Ethical Considerations Perspective Long-Term Follow-Up Research Protocols for Investigational Treatment With DBS Summary Future Directions References Further Reading 88 - Neuromodulation in Anorexia Nervosa Introduction Clinical Aspects Neurobiology and Neuroimaging Clinical Treatment and Refractory Anorexia Nervosa Nervosa Neuromodulation Deep Brain Stimulation Ethical Aspects Conclusions References 89 - Deep Brain Stimulation for Alcoholism Introduction and Background Scientific Rationale for the Use of DBS for Alcoholism Animal Studies Human Studies Mechanisms of Action References 90 - Surgical Treatment for Refractory Drug Addiction Overview The Development of Stereotactic Surgery for Drug Addiction The Pathophysiology of Drug Addiction Neurosurgical Procedures Mechanisms Future Expectations Conclusions References 91 - Subgenual Cingulate Deep Brain Stimulation for Treatment-Resistant Depression Introduction Overview of MDD Diagnosis of MDD Antidepressants and Psychotherapy Treatment-Resistant Depression Surgical Interventions for MDD: Background Ablative Surgery Deep Brain Stimulation DBS of the Subgenual Cingulate Cortex Rationale A Network Model of MDD The SCC as a Critical Region in the Regulation of Mood Feasibility Study of SCC DBS Efficacy and Safety of SCC DBS Safety of SCC DBS Issues in Optimizing Patient Outcomes in SCC DBS Patient Selection for SCC DBS Targeting the SCC Basics of Diffusion-Weighted Imaging Development of DWI-Based Targeting Methods for SCC DBS Implementation Mechanisms of Action Summary and Future Directions References 92 - Cortical Stimulation for Depression Introduction Electroconvulsive Therapy Transcranial Magnetic Stimulation Transcranial Direct Current Stimulation Transcranial Direct Current Stimulation as an Instrument to Modulate Cortical Excitability Safety of Transcranial Direct Current Stimulation Transcranial Direct Current Stimulation Versus Antidepressant Medications Future Directions Conclusion References