Resources:Electrical stimulation of cranial nerves in cognition and disease

Free resource

Title	Electrical stimulation of cranial nerves in cognition and disease
Authors	Devin Adair · Dennis Truong · Zeinab Esmaeilpour · Nigel Gebodh · Helen Borges · Libby Ho · J. Douglas Bremner · Bashar W. Badran · Vitaly Napadow · Vincent P. Clark · Marom Bikson
Source	Document
Original	https://www.brainstimjrnl.com/action/showPdf?pii=S1935-861X%2820%2930041-3
Date	18 July 2019
Journal	Brain Stimulation
DOI	10.1016/j.brs.2020.02.019
PUBMED	https://pubmed.ncbi.nlm.nih.gov/32289703/
License	CC BY
This resource has been identified as a Free Scientific Resource, this is why Masticationpedia presents it here as a mean of gratitude toward the Authors, with appreciation for their choice of releasing it open to anyone's access

Electrical stimulation of cranial nerves in cognition and disease

Free resource by Devin Adair  · Dennis Truong · Zeinab Esmaeilpour  · Nigel Gebodh · Helen Borges  · Libby Ho  · J. Douglas Bremner  · Bashar W. Badran  · Vitaly Napadow  · Vincent P. Clark  · Marom Bikson

Abstract

The cranial nerves are the pathways through which environmental information (sensation) is directlycommunicated to the brain, leading to perception, and giving rise to higher cognition. Because cranialnerves determine and modulate brain function, invasive and non-invasive cranial nerve electricalstimulation methods have applications in the clinical, behavioral, and cognitive domains. Among otherneuromodulation approaches such as peripheral, transcranial and deep brain stimulation, cranial nervestimulation is unique in allowing axon pathway-specific engagement of brain circuits, including thalamo-cortical networks. In this review we amalgamate relevant knowledge of 1) cranial nerve anatomy andbiophysics; 2) evidence of the modulatory effects of cranial nerves on cognition; 3) clinical and behav-ioral outcomes of cranial nerve stimulation; and 4) biomarkers of nerve target engagement includingphysiology, electroencephalography, neuroimaging, and behavioral metrics. Existing non-invasivestimulation methods cannot feasibly activate the axons of only individual cranial nerves. Even withinvasive stimulation methods, selective targeting of one nervefiber type requires nuance since eachnerve is composed of functionally distinct axon-types that differentially branch and can anastomose ontoother nerves. None-the-less, precisely controlling stimulation parameters can aid in affecting distinct setsof axons, thus supporting specific actions on cognition and behavior. To this end, a rubric for reproducibledose-response stimulation parameters is defined here. Given that afferent cranial nerve axons projectdirectly to the brain, targeting structures (e.g. thalamus, cortex) that are critical nodes in higher orderbrain networks, potent effects on cognition are plausible. We propose an intervention design frameworkbased on driving cranial nerve pathways in targeted brain circuits, which are in turn linked to specifichigher cognitive processes. State-of-the-art currentflow models that are used to explain and designcranial-nerve-activating stimulation technology require multi-scale detail that includes: gross anatomy;skull foramina and superficial tissue layers; and precise nerve morphology. Detailed simulations alsopredict that some non-invasive electrical or magnetic stimulation approaches that do not intend tomodulate cranial nerves per se, such as transcranial direct current stimulation (tDCS) and transcranialmagnetic stimulation (TMS), may also modulate activity of specific cranial nerves. Much prior cranialnerve stimulation work was conceptually limited to the production of sensory perception, with indi-vidual titration of intensity based on the level of perception and tolerability. However, disregardingsensory emulation allows consideration of temporal stimulation patterns (axon recruitment) thatmodulate the tone of cortical networks independent of sensory cortices, without necessarily titratingperception. For example, leveraging the role of the thalamus as a gatekeeper for information to thecerebral cortex, preventing or enhancing the passage of specific information depending on the behavioralstate. We show that properly parameterized computational models at multiple scales are needed to rationally optimize neuromodulation that target sets of cranial nerves, determining which and howspecific brain circuitries are modulated, which can in turn influence cognition in a designed manner.

©2020 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Introduction

Cognition is conceptualized as the processing of informationacquired through the senses. The central nervous system (CNS;nerves within the brain and spine) integrates and responds tosignals transmitted by the peripheral nervous system (PNS; nervesoutside the brain and spine), whose primary function is to connectthe CNS with the rest of the body and the environment [1]. Thecranial nerves are a specialized part of the PNS that emerge directlyfrom the brain rather than through the spine and include both af-ferents and efferents. Afferent cranial nerve axons convey sensoryinformationdsight, hearing, taste (gustation), touch (heat, pres-sure, pain, proprioception), smell (olfaction), interoception (inputfrom the gut and internal organs), and equilibriumdto the brain.Efferent cranial nerves’axons regulate muscles (smooth, skeletal,and cardiac) and glands (either directly or through a postganglionicaxon;Table 1). In contrast to other peripheral nerves thatfirst routethrough the spinal cord, cranial nerves project directly through theskull into the brain, which makes them a special target for neuro-modulation. For each cranial nerve, there is a portion that is rela-tively accessible (extra-cranial), and each nerve is intimately linkedto perception and regulation of CNS function, including established“bottom-up”functions in cognition and clinical disorders [2e4].Here we develop a formalism to design cranial nerve stimulationby leveraging insight from modern biomedical engineering andneuroscience (i.e. biomarkers)ein order to target specificcognitiveconstructs and behaviors that may be linked to neuropsychiatricdisorders. We focus mainly on nerves that contain a major sensory(or afferent) component, however in some cases it can be chal-lenging to disambiguate the cognitive effects of cranial nervesstimulation on afferents vs. efferents (see sec.5). Our overallapproach is to focus on each afferent cranial nerve that modulates aspecific brain circuit–including those circuits involved in lower andhigher-level processes - providing a rational basis to target specificcognitive functions by optimized cranial nerve stimulation. Indeed,while transcranial approaches (e.g. TMS and tDCS) or some invasiveapproaches (e.g. certain forms of DBS) inevitably stimulate a com-plex constellation of neurons, cranial nerve stimulation allows (withlimitations discussed) activation of targeted pathways into the CNSusing minimally or non-invasive technology.There is a large body of literature on the modulation of cranialnerves by electrical stimulation for both therapeutic and experi-mental applications; however, these studies are variable in meth-odology and conclusions. The clinical neuroanatomy of each cranialnerve have been explored [5], but nuance continues to emerge inanatomy and function [6,7]. Some of the earliest applications ofelectrical stimulation to cranial nerves were to treat neurologicaldisorders such as seizures [8,9] and sensory dysfunctions [e.g.,vision loss, equilibrium damage; 10, 11]. Subsequent inclusion ofbroader clinical indicationsdincluding neuropsychiatric disorders–have furthered knowledge of how activity of early sensory sys-tems through cranial nerves can influence higher cognitive pro-cesses [12e14]. This improved understanding has driven theexpansion of devices geared towards a variety of applicationsincluding treatment of specific disorders as well as enhancement ofcognitive and other functions [15e17]