Regaining Consciousness: The Effect of Vagal Nerve Stimulation on a Patient in a Permanent Vegetative State

Regaining Consciousness: The Effect of Vagal Nerve Stimulation on a Patient in a Permanent... Patients in a permanent vegetative state remain in a circumstance of partial arousal and limited wakefulness, if at all. The ability to restore consciousness in a patient within a vegetative state has been the elusive holy grail of neuroscientists and clinicians. Many experimental trials through deep brain stimulation, transcortical magnetic stimulation, and pharmaceutical stimulants have been attempted but with resulted in limited success. Ongoing neuroanatomic studies have shed some light on the pathophysiology of patients within a permanent vegetative state. Disruptions within the cortico–cortical and thalamo–cortical pathways have been postulated to be the neuroanatomic cause behind this condition. Expectantly, the restoration of connectivity between these long white-matter tracts has been the agent of the rare spontaneous recoveries seen in patients formerly in a vegetative state. Instead of restoring injured white matter connections, what if there was a way to make the remaining white matter connections work harder? A study by Corazzol et al1 found a way to do so through vagal nerve stimulation (VNS). The vagus nerve carries afferent connections to the deep nuclei of the brain via the nucleus solitarius. These afferent connections have multiple targets, which include the thalamus, amygdala, reticular formation, hippocampus, raphe nucleus, and the locus coeruleus. These targets are all foci that have the plausibility to facilitate global neurostimulation. For their trial, they selected a 35-yr-old male who was involved in a motor vehicle accident 15 yr ago. This incident left him with a severe traumatic brain injury and has been in a permanent vegetative state since. Behavioral assessments, fluorodeoxyglucose - positron emission tomography (FDG-PET) scans, and electroencephalogram (EEG) studies were performed prior to VNS implantation. The patient underwent a successful implantation and had his VNS programmed to 0.25 mA on his first postoperative day. Throughout the 6-mo observation period, the patient's VNS was incrementally programmed from 0.25 mA to 1.5 mA. Objective improvement in the behavioral assessments were observed, with the patient now tracking the examiner through voice, his eyes opening wider, and his emotions being shown through a smile and tearing when his preferred music was playing. Based on objective scoring, his level of consciousness went from a “vegetative state” to a “minimally conscious state.” EEG findings also confirmed increased neural activity. The Figure depicts the before and after EEG findings of improved cerebral activity following VNS implantation. Significantly increased theta-band activity also promoted this patient to a “minimally conscious state.” These theta waves were predominantly seen over the right inferior parietal and the parieto-temporal-occipital border, a region known to be instrumental in conscious awareness. Figure. View largeDownload slide Information sharing increases after vagus nerve stimulation over centroposterior regions. A, Sagittal (left) and coronal (right) views of weighted symbolic mutual information (wSMI) shared by all channels pre- and post-VNS (top and bottom, respectively). For visual clarity, only links with wSMI higher than 0.025 are shown. B, Topographies of the median wSMI that each EEG channel shares with all the other channels pre- and post-VNS (top and bottom, respectively). The bar graph represents the median wSMI over right centroposterior electrodes (darker dots) that significantly increases post-VNS (permutation test over sessions: Wilcoxon test, P = .0266). C, Localization of the most VNS-reactive theta source showing significant increase of information sharing post-VNS. Sources’ localization is presented over the patient's cortical surface (probability map, sLoreta current source density: light blue scale) combined with his FDG-PET metabolism (gray scale) as measured 3 mo post-VNS. The source was localized in the inferior parietal lobule. The bar graph represents the mean wSMI shared with all other selected sources pre- and post-VNS (dark gray and light gray, respectively) (permutation test over sessions: Wilcoxon test, P < .01 Bonferroni corrected). CRS-R clinical score increased as a function of information sharing over a cortical posterior theta network (Robust regression, P = .0015). Reprinted from Current Biology, 27(18), Corazzol M, Lio G, Lefevre A, et al, Restoring consciousness with vagus nerve stimulation, R994-R996, 2017,1 with permission from Elsevier. Figure. View largeDownload slide Information sharing increases after vagus nerve stimulation over centroposterior regions. A, Sagittal (left) and coronal (right) views of weighted symbolic mutual information (wSMI) shared by all channels pre- and post-VNS (top and bottom, respectively). For visual clarity, only links with wSMI higher than 0.025 are shown. B, Topographies of the median wSMI that each EEG channel shares with all the other channels pre- and post-VNS (top and bottom, respectively). The bar graph represents the median wSMI over right centroposterior electrodes (darker dots) that significantly increases post-VNS (permutation test over sessions: Wilcoxon test, P = .0266). C, Localization of the most VNS-reactive theta source showing significant increase of information sharing post-VNS. Sources’ localization is presented over the patient's cortical surface (probability map, sLoreta current source density: light blue scale) combined with his FDG-PET metabolism (gray scale) as measured 3 mo post-VNS. The source was localized in the inferior parietal lobule. The bar graph represents the mean wSMI shared with all other selected sources pre- and post-VNS (dark gray and light gray, respectively) (permutation test over sessions: Wilcoxon test, P < .01 Bonferroni corrected). CRS-R clinical score increased as a function of information sharing over a cortical posterior theta network (Robust regression, P = .0015). Reprinted from Current Biology, 27(18), Corazzol M, Lio G, Lefevre A, et al, Restoring consciousness with vagus nerve stimulation, R994-R996, 2017,1 with permission from Elsevier. FDG-PET acquisition following VNS implantation also revealed increased metabolic activity over the occipito-parieto-frontal regions, the basal ganglia, and the thalamus. The increase in activity at these regions could be the source behind the increase theta activity and thus increased wakefulness as a result of vagal nerve stimulation. The revelation within this trial displays the potential for the restoration of consciousness following VNS implantation, albeit in this limited, single-subject study. If proven to be successful in larger studies, this would add to the list of other, proven VNS benefits, which include seizure control and mood stabilization. VNS has also been experimented in the management of Alzheimer's disease, obesity, chronic alcoholism, and chronic heart failure. With approximately 25 000 patients in the United States living in a vegetative state, VNS is a promising direction for a potential awakening. The mechanism by which this occurs continues to be a humble reminder of the brain's mysterious, yet modifiable, connections. REFERENCE 1. Corazzol M, Lio G, Lefevre A et al.   Restoring consciousness with vagus nerve stimulation. Curr Biol . 2017; 27( 18): R994- R996. Google Scholar CrossRef Search ADS PubMed  Copyright © 2017 by the Congress of Neurological Surgeons http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neurosurgery Oxford University Press

Regaining Consciousness: The Effect of Vagal Nerve Stimulation on a Patient in a Permanent Vegetative State

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Oxford University Press
Copyright
Copyright © 2017 by the Congress of Neurological Surgeons
ISSN
0148-396X
eISSN
1524-4040
D.O.I.
10.1093/neuros/nyx597
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Abstract

Patients in a permanent vegetative state remain in a circumstance of partial arousal and limited wakefulness, if at all. The ability to restore consciousness in a patient within a vegetative state has been the elusive holy grail of neuroscientists and clinicians. Many experimental trials through deep brain stimulation, transcortical magnetic stimulation, and pharmaceutical stimulants have been attempted but with resulted in limited success. Ongoing neuroanatomic studies have shed some light on the pathophysiology of patients within a permanent vegetative state. Disruptions within the cortico–cortical and thalamo–cortical pathways have been postulated to be the neuroanatomic cause behind this condition. Expectantly, the restoration of connectivity between these long white-matter tracts has been the agent of the rare spontaneous recoveries seen in patients formerly in a vegetative state. Instead of restoring injured white matter connections, what if there was a way to make the remaining white matter connections work harder? A study by Corazzol et al1 found a way to do so through vagal nerve stimulation (VNS). The vagus nerve carries afferent connections to the deep nuclei of the brain via the nucleus solitarius. These afferent connections have multiple targets, which include the thalamus, amygdala, reticular formation, hippocampus, raphe nucleus, and the locus coeruleus. These targets are all foci that have the plausibility to facilitate global neurostimulation. For their trial, they selected a 35-yr-old male who was involved in a motor vehicle accident 15 yr ago. This incident left him with a severe traumatic brain injury and has been in a permanent vegetative state since. Behavioral assessments, fluorodeoxyglucose - positron emission tomography (FDG-PET) scans, and electroencephalogram (EEG) studies were performed prior to VNS implantation. The patient underwent a successful implantation and had his VNS programmed to 0.25 mA on his first postoperative day. Throughout the 6-mo observation period, the patient's VNS was incrementally programmed from 0.25 mA to 1.5 mA. Objective improvement in the behavioral assessments were observed, with the patient now tracking the examiner through voice, his eyes opening wider, and his emotions being shown through a smile and tearing when his preferred music was playing. Based on objective scoring, his level of consciousness went from a “vegetative state” to a “minimally conscious state.” EEG findings also confirmed increased neural activity. The Figure depicts the before and after EEG findings of improved cerebral activity following VNS implantation. Significantly increased theta-band activity also promoted this patient to a “minimally conscious state.” These theta waves were predominantly seen over the right inferior parietal and the parieto-temporal-occipital border, a region known to be instrumental in conscious awareness. Figure. View largeDownload slide Information sharing increases after vagus nerve stimulation over centroposterior regions. A, Sagittal (left) and coronal (right) views of weighted symbolic mutual information (wSMI) shared by all channels pre- and post-VNS (top and bottom, respectively). For visual clarity, only links with wSMI higher than 0.025 are shown. B, Topographies of the median wSMI that each EEG channel shares with all the other channels pre- and post-VNS (top and bottom, respectively). The bar graph represents the median wSMI over right centroposterior electrodes (darker dots) that significantly increases post-VNS (permutation test over sessions: Wilcoxon test, P = .0266). C, Localization of the most VNS-reactive theta source showing significant increase of information sharing post-VNS. Sources’ localization is presented over the patient's cortical surface (probability map, sLoreta current source density: light blue scale) combined with his FDG-PET metabolism (gray scale) as measured 3 mo post-VNS. The source was localized in the inferior parietal lobule. The bar graph represents the mean wSMI shared with all other selected sources pre- and post-VNS (dark gray and light gray, respectively) (permutation test over sessions: Wilcoxon test, P < .01 Bonferroni corrected). CRS-R clinical score increased as a function of information sharing over a cortical posterior theta network (Robust regression, P = .0015). Reprinted from Current Biology, 27(18), Corazzol M, Lio G, Lefevre A, et al, Restoring consciousness with vagus nerve stimulation, R994-R996, 2017,1 with permission from Elsevier. Figure. View largeDownload slide Information sharing increases after vagus nerve stimulation over centroposterior regions. A, Sagittal (left) and coronal (right) views of weighted symbolic mutual information (wSMI) shared by all channels pre- and post-VNS (top and bottom, respectively). For visual clarity, only links with wSMI higher than 0.025 are shown. B, Topographies of the median wSMI that each EEG channel shares with all the other channels pre- and post-VNS (top and bottom, respectively). The bar graph represents the median wSMI over right centroposterior electrodes (darker dots) that significantly increases post-VNS (permutation test over sessions: Wilcoxon test, P = .0266). C, Localization of the most VNS-reactive theta source showing significant increase of information sharing post-VNS. Sources’ localization is presented over the patient's cortical surface (probability map, sLoreta current source density: light blue scale) combined with his FDG-PET metabolism (gray scale) as measured 3 mo post-VNS. The source was localized in the inferior parietal lobule. The bar graph represents the mean wSMI shared with all other selected sources pre- and post-VNS (dark gray and light gray, respectively) (permutation test over sessions: Wilcoxon test, P < .01 Bonferroni corrected). CRS-R clinical score increased as a function of information sharing over a cortical posterior theta network (Robust regression, P = .0015). Reprinted from Current Biology, 27(18), Corazzol M, Lio G, Lefevre A, et al, Restoring consciousness with vagus nerve stimulation, R994-R996, 2017,1 with permission from Elsevier. FDG-PET acquisition following VNS implantation also revealed increased metabolic activity over the occipito-parieto-frontal regions, the basal ganglia, and the thalamus. The increase in activity at these regions could be the source behind the increase theta activity and thus increased wakefulness as a result of vagal nerve stimulation. The revelation within this trial displays the potential for the restoration of consciousness following VNS implantation, albeit in this limited, single-subject study. If proven to be successful in larger studies, this would add to the list of other, proven VNS benefits, which include seizure control and mood stabilization. VNS has also been experimented in the management of Alzheimer's disease, obesity, chronic alcoholism, and chronic heart failure. With approximately 25 000 patients in the United States living in a vegetative state, VNS is a promising direction for a potential awakening. The mechanism by which this occurs continues to be a humble reminder of the brain's mysterious, yet modifiable, connections. REFERENCE 1. Corazzol M, Lio G, Lefevre A et al.   Restoring consciousness with vagus nerve stimulation. Curr Biol . 2017; 27( 18): R994- R996. Google Scholar CrossRef Search ADS PubMed  Copyright © 2017 by the Congress of Neurological Surgeons

Journal

NeurosurgeryOxford University Press

Published: Mar 1, 2018

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