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      Non-invasive Vagus Nerve Stimulation in Treatment of Disorders of Consciousness – Longitudinal Case Study

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          Abstract

          Neuromodulatory electroceuticals such as vagus nerve stimulation have been recently gaining traction as potential rehabilitation tools for disorders of consciousness (DoC). We present a longitudinal case study of non-invasive auricular vagus nerve stimulation (taVNS) in a patient diagnosed with chronic unresponsive wakefulness syndrome (previously known as vegetative state). Over a period of 6 months we applied taVNS daily and regularly evaluated the patient’s behavioral outcomes using Coma Recovery Scale – Revised. We also took electrophysiological measures: resting state electroencephalography (EEG), heart rate (HR) and heart rate variability (HRV). All these methods revealed signs of improvement in the patient’s condition. The total CRS-R scores fluctuated but rose from 4 and 6 at initial stages to the heights of 12 and 13 in the 3rd and 5th month, which would warrant a change in diagnosis to a Minimally Conscious State. Scores obtained in a 2 months follow-up period, though, suggest this may not have been a lasting improvement. Behavioral signs of recovery are triangulated by EEG frequency spectrum profiles with re-emergence of a second oscillatory peak in the alpha range, which has been shown to characterize aware people. However, sustained spontaneous theta oscillations did not predictably diminish, which most likely reflects structural brain damage. ECG measures revealed a steady decrease in pre-stimulation HR combined with an increase in HRV-HR. This suggests a gradual withdrawal of sympathetic and an increase in parasympathetic control of the heart, which the previous literature has also linked with DoC improvements. Together, this study suggests that taVNS stimulation holds promise as a DoC treatment.

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          Most cited references49

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          Interoceptive inference, emotion, and the embodied self.

          The concept of the brain as a prediction machine has enjoyed a resurgence in the context of the Bayesian brain and predictive coding approaches within cognitive science. To date, this perspective has been applied primarily to exteroceptive perception (e.g., vision, audition), and action. Here, I describe a predictive, inferential perspective on interoception: 'interoceptive inference' conceives of subjective feeling states (emotions) as arising from actively-inferred generative (predictive) models of the causes of interoceptive afferents. The model generalizes 'appraisal' theories that view emotions as emerging from cognitive evaluations of physiological changes, and it sheds new light on the neurocognitive mechanisms that underlie the experience of body ownership and conscious selfhood in health and in neuropsychiatric illness. Copyright © 2013 Elsevier Ltd. All rights reserved.
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            Kubios HRV--heart rate variability analysis software.

            Kubios HRV is an advanced and easy to use software for heart rate variability (HRV) analysis. The software supports several input data formats for electrocardiogram (ECG) data and beat-to-beat RR interval data. It includes an adaptive QRS detection algorithm and tools for artifact correction, trend removal and analysis sample selection. The software computes all the commonly used time-domain and frequency-domain HRV parameters and several nonlinear parameters. There are several adjustable analysis settings through which the analysis methods can be optimized for different data. The ECG derived respiratory frequency is also computed, which is important for reliable interpretation of the analysis results. The analysis results can be saved as an ASCII text file (easy to import into MS Excel or SPSS), Matlab MAT-file, or as a PDF report. The software is easy to use through its compact graphical user interface. The software is available free of charge for Windows and Linux operating systems at http://kubios.uef.fi. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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              A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health.

              The intimate connection between the brain and the heart was enunciated by Claude Bernard over 150 years ago. In our neurovisceral integration model we have tried to build on this pioneering work. In the present paper we further elaborate our model and update it with recent results. Specifically, we performed a meta-analysis of recent neuroimaging studies on the relationship between heart rate variability and regional cerebral blood flow. We identified a number of regions, including the amygdala and ventromedial prefrontal cortex, in which significant associations across studies were found. We further propose that the default response to uncertainty is the threat response and may be related to the well known negativity bias. Heart rate variability may provide an index of how strongly 'top-down' appraisals, mediated by cortical-subcortical pathways, shape brainstem activity and autonomic responses in the body. If the default response to uncertainty is the threat response, as we propose here, contextual information represented in 'appraisal' systems may be necessary to overcome this bias during daily life. Thus, HRV may serve as a proxy for 'vertical integration' of the brain mechanisms that guide flexible control over behavior with peripheral physiology, and as such provides an important window into understanding stress and health. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                06 May 2022
                2022
                : 16
                : 834507
                Affiliations
                [1] 1Faculty of Psychology, University of Warsaw , Warsaw, Poland
                [2] 2Institute of Psychology, Jagiellonian University , Kraków, Poland
                [3] 3Department of Cognitive Science, Faculty of Humanities, Nicolaus Copernicus University in Toruń , Toruń, Poland
                Author notes

                Edited by: Brian Kliszczewicz, Kennesaw State University, United States

                Reviewed by: Wiktor Jedrzejczak, Institute of Physiology and Pathology of Hearing (IFPS), Poland; Christopher Austelle, Medical University of South Carolina, United States

                *Correspondence: Albertyna Osińska, albertyna.osinska@ 123456psych.uw.edu.pl

                This article was submitted to Autonomic Neuroscience, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2022.834507
                9120963
                35600632
                2f73fb6a-0de0-4286-a3b2-3629ad67ef9a
                Copyright © 2022 Osińska, Rynkiewicz, Binder, Komendziński, Borowicz and Leszczyński.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 December 2021
                : 29 March 2022
                Page count
                Figures: 5, Tables: 5, Equations: 0, References: 50, Pages: 14, Words: 9936
                Categories
                Neuroscience
                Original Research

                Neurosciences
                vagus nerve stimulation,tavns,disorders of consciousness,coma,unresponsive wakefulness syndrome (uws),eeg,hrv

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