Vagus Nerve Stimulation

Preface to the Series
Preface
	Scoping Table of Contents for All Chapters
	Introduction to the Vagus Nerve
	Invasive and Non-invasive Vagus Nerve Stimulation
	References
Contents
Contributors
Chapter 1: Vagus Nerve Stimulation in Peripheral Targets
	1 Introduction
	2 Peripheral Nervous and Musculoskeletal System Disorders
	3 Digestive System
	4 Respiratory System
	5 Obesity and Endocrine System
	6 Peripheral Circulatory System
	7 Other Peripheral Disorders
	8 Conclusion
	References
Chapter 2: Vagal Nerve Stimulation Through the Lens of the Polyvagal Theory: Recruiting Neurophysiological Mechanisms to Dampe...
	1 Introduction: Insights into Why Vagal Nerve Stimulation Optimizes Homeostatic Functions and Reduces Mental Health Symptoms
	2 The Emergence of the Ventral Vagal Complex and the Social Engagement System
	3 Sensory Pathways from the Target Organs of the Social Engagement System Provide Potent Input to the Source Nuclei Regulating...
	4 Vagal Pathways
	5 Vagal Nerve Stimulation: Assumed Mode of Action
	6 Ventral Vagal Complex: A Portal for Vagal Nerve Stimulation
	7 Role of Afferents in Vagal Nerve Stimulation
	8 Emphasis on Vagal Afferents: Aortic Depressor Nerve
	9 Recruiting the Acoustic Efferent Limb of the Social Engagement System: A Portal to Stimulate Vagal Efferent Activity
	10 Summary
	References
Chapter 3: Heart Rate Variability as a Biomarker for Electrical Vagus Nerve Stimulation
	1 Introduction
		1.1 Working Mechanisms of Electrical Vagus Nerve Stimulation Underlying Effects on Heart Rate Variability
		1.2 Effects of Electrical Vagus Nerve Stimulation on Cardiac Vagal Activity: State of Evidence
			1.2.1 Transcutaneous Vagus Nerve Stimulation and Cardiac Vagal Activity
			1.2.2 Implanted Vagus Nerve Stimulation and Cardiac Vagal Activity
	2 Materials
		2.1 Electrical Vagus Nerve Stimulation
		2.2 Cardiac Vagal Activity
	3 Methods
		3.1 Considerations for a Proper Cardiac Vagal Activity Measurement During Electrical Vagus Nerve Stimulation
		3.2 Designing Studies on the Effects of eVNS with Cardiac Vagal Activity as a Biomarker
	4 Conclusion
	References
Chapter 4: Vagus Nerve Manipulation and Microglial Plasticity in the Prenatal Brain
	1 Introduction
		1.1 Neuroimmunology: Quis Custodiet Ipsos Custodes?
		1.2 Cholinergic Anti-inflammatory Pathway and Microglia
		1.3 VNS and Cerebral Blood Flow: Is There a Link Between Neuroinflammation and rCBF?
	2 Methodology
		2.1 Anesthesia and Surgical Procedure
		2.2 Experimental Protocol
		2.3 Immunofluorescence Staining and Microscopy
		2.4 Quantification of Iba-1 Signal
		2.5 Measurement of Cerebral Blood Flow
		2.6 Statistical Approach
	3 Results
		3.1 Systemic Inflammatory Response: IL-6
		3.2 Vagus Nerve Signaling Modulates Microglial Phenotype
			3.2.1 Effects of Vagus Nerve Manipulation on Iba-1 Expression in the Hippocampus
			3.2.2 Effects of Vagus Nerve Manipulation on Microglial Morphometry in the Hippocampus
			3.2.3 Batch Effects: Accounting for Measurements of Microglial Activity Made During Different Time Points
		3.3 Vagus Nerve Activity Modulates rCBF
	4 Discussion
		4.1 Vagotomy Reduces the Activated State of Microglia Exposed to Systemic Inflammation Induced by LPS
		4.2 Under the Condition of Vagotomy, Iba-1 Expression in the Fetal Hippocampus Depends on LPS Dosage
		4.3 Afferent or Efferent VNS Restores Microglial Phenotype
		4.4 VNS Modulates rCBF
		4.5 Therapeutic Implications for VNS in the Treatment of Neurodegenerative Disorders
		4.6 Implications of VNS in Studies of Perinatal Brain Development and Function: New Insights and Opportunities
		4.7 Significance
	References
Chapter 5: Neonatal Sepsis Is Diminished by Cervical Vagus Nerve Stimulation and Tracked Noninvasively by ECG: A Pilot Report ...
	1 Introduction
	2 Materials and Methods
		2.1 Ethics Statement
		2.2 Anesthesia
		2.3 Surgery
		2.4 Data Acquisition
		2.5 Experimental Protocol
			2.5.1 Baseline
			2.5.2 Induction of Endotoxemia with LPS
			2.5.3 Cytokines Assay
			2.5.4 Hematology
			2.5.5 Data Analysis
	3 Results
		3.1 Cardiovascular Effects
		3.2 Cytokine Responses
		3.3 HRV Behavior
		3.4 VENG Patterns in Response to LPS and VNS
		3.5 HRV and VENG Inflammatory Index: Machine Learning Approach
	4 Discussion
	5 Limitations
	6 Future Directions
	References
Chapter 6: Cognitive Enhancement Through Vagus Nerve Stimulation: Methodological Considerations for Behavioral Studies in Rats
	1 Introduction
		1.1 VNS as a Potential Treatment for Cognitive Impairment
	2 Materials
		2.1 Subjects
		2.2 Vagus Nerve Cuff Electrodes
		2.3 Behavioral Apparatus (Touchscreen Operant Chambers)
			2.3.1 Touchscreen Chamber Design
		2.4 Stimulation Apparatus
	3 Methods
		3.1 Surgical Implantation of VNS Cuffs
			3.1.1 Placement of Skull Anchor Screws
			3.1.2 Implantation of Cuff Around the Left Vagus Nerve
			3.1.3 Special Considerations for Working with Aged Rats
			3.1.4 Surgical Protocols Specific to Aged Rats
		3.2 In Vivo Assessment of VNS Cuff Viability
			3.2.1 Electrochemical Impedance Spectroscopy Measurements
			3.2.2 Using a Vagal-Mediated Autonomic Reflex to Assess Electrode Function
		3.3 Assessing Effects of VNS on Cognition
			3.3.1 Configuring Electrodes for Cathodal Stimulation
			3.3.2 Cognitive Flexibility/Reversal Learning
			3.3.3 VNS Enhances Reversal Learning
			3.3.4 Stimulus Frequency Parameters
			3.3.5 Evaluating ``Off-Target´´ Effects of VNS
	4 Conclusions
	References
Chapter 7: Influence of Vagus Nerve Stimulation on Mood and Associated Disorders
	1 The Vagus Nerve
	2 Vagal Nerve Stimulation
	3 VNS and Depression
		3.1 Clinical Studies of VNS in Treatment-Resistant Depression
		3.2 Preclinical Studies of VNS
	4 Potential Mechanisms
		4.1 Inflammation
		4.2 Neurogenesis
		4.3 Effects on Neurotransmitters
		4.4 Safety and Side Effects
		4.5 Transcutaneous VNS
	5 VNS and Anxiety
	6 VNS and Sleep
	References
Chapter 8: Transcutaneous Vagal Nerve Stimulation in Trauma Spectrum Psychiatric Disorders
	1 Introduction
	2 The Vagus Nerve as a Target of Treatment for Trauma Spectrum Disorders
		2.1 Physiological Correlates of Vagal Nerve Stimulation
		2.2 Vagal Nerve Stimulation as a Modulator of Neuroplasticity
		2.3 Effects of Vagal Nerve Stimulation on Brain Function: Relevance to Stress-Related Psychiatric Disorders
	3 Studies of Transcutaneous Vagal Nerve Stimulation in PTSD and Trauma
	4 Conclusions
	References
Chapter 9: Vagus Nerve Stimulation for Migraine and Cluster Headaches
	1 Introduction
	2 Mechanism of Action
		2.1 Cluster Studies
	3 PREVA Study
	4 ACT-1
	5 ACT 2 Study
		5.1 Migraine Studies
			5.1.1 The PRESTO Study
			5.1.2 The EVENT Study
	6 Conclusion
	References
Chapter 10: Vagus Nerve Stimulation and Language Learning
	1 Introduction
	2 Materials and Other Methodological Considerations
		2.1 Participant Selection and Experimental Design
		2.2 Linguistic Training Materials
		2.3 Type of Training
		2.4 Assessment of Learning
		2.5 Stimulation Parameters
	3 Methods: Illustrative Examples of taVNS Studies on Language Learning
	4 Notes
	References
Index