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Non-invasive Vagal Nerve Stimulation Effects on Hyperarousal and Autonomic State in Patients with Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury: Preliminary Evidence.

ABSTRACT: Posttraumatic stress disorder (PTSD) is a reaction to trauma that results in a chronic perception of threat, precipitating mobilization of the autonomic nervous system, and may be reflected by chronic disinhibition of limbic structures. A common injury preceding PTSD in veterans is mild traumatic brain injury (mTBI). This may be due to the vulnerability of white matter in these networks and such damage may affect treatment response. We evaluated transcutaneous vagal nerve stimulation (tVNS), a non-invasive, low-risk approach that may alter the functions of the limbo-cortical and peripheral networks underlying the hyperarousal component of PTSD and thus improve patient health and well-being. In this single visit pilot study evaluating the impact of tVNS in 22 combat veterans, we used a between-subjects design in people with either PTSD with preceding mTBI or healthy controls. Participants were randomized into stimulation or sham groups and completed a posturally modulated autonomic assessment and emotionally modulated startle paradigm. The primary measures used were respiratory sinus arrhythmia (high-frequency heart rate variability) during a tilt-table procedure derived from an electrocardiogram, and skin conductance changes in response to acoustic startle while viewing emotional images (International Affective Picture System). The stimulation was well tolerated and resulted in improvements in vagal tone and moderation of autonomic response to startle, consistent with modulation of autonomic state and response to stress in this population. Our results suggest that tVNS affects systems underlying emotional dysregulation in this population and, therefore, should be further evaluated and developed as a potential treatment tool for these patients.

SUBMITTER: Lamb DG

PROVIDER: S-EPMC5534856 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:ObjectivesMilitary service members risk acquiring posttraumatic stress disorder (PTSD) and mild-traumatic brain injury (mTBI), with high comorbidity. Owing to overlapping symptomatology in chronic mTBI or postconcussion syndrome (PCS) and PTSD, it is difficult to assess the etiology of a patient's condition without objective measures. Using resting-state functional MRI in a novel framework, we tested the hypothesis that their neural signatures are characterized by functionally hyperconnected brain regions which are less variable over time. Additionally, we predicted that such connectivities possessed the highest ability in predicting the diagnostic membership of a novel subject (top-predictors) in addition to being statistically significant.MethodsU.S. Army Soldiers (N?=?87) with PTSD and comorbid PCS?+?PTSD were recruited along with combat controls. Static and dynamic functional connectivities were evaluated. Group differences were obtained in accordance with our hypothesis. Machine learning classification (MLC) was employed to determine top predictors.ResultsFrom whole-brain connectivity, we identified the hippocampus-striatum connectivity to be significantly altered in accordance with our hypothesis. Diffusion tractography revealed compromised white-matter integrity between aforementioned regions only in the PCS?+?PTSD group, suggesting a structural etiology for the PCS?+?PTSD group rather than being an extreme subset of PTSD. Employing MLC, connectivities provided worst-case accuracy of 84% (9% more than psychological measures). Additionally, the hippocampus-striatum connectivities were found to be top predictors and thus a potential biomarker of PTSD/mTBI.ConclusionsPTSD/mTBI are associated with hippocampal-striatal hyperconnectivity from which it is difficult to disengage, leading to a habit-like response toward episodic traumatic memories, which fits well with behavioral manifestations of combat-related PTSD/mTBI. Hum Brain Mapp 38:2843-2864, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Project description:Posttraumatic stress disorder (PTSD) is a highly disabling condition associated with alterations in multiple neurobiological systems, including increases in inflammatory and sympathetic function, responsible for maintenance of symptoms. Treatment options including medications and psychotherapies have limitations. We previously showed that transcutaneous Vagus Nerve Stimulation (tcVNS) blocks inflammatory (interleukin (IL)-6) responses to stress in PTSD. The purpose of this study was to assess the effects of tcVNS on PTSD symptoms and inflammatory responses to stress. Twenty patients with PTSD were randomized to double blind active tcVNS (N=9) or sham (N=11) stimulation in conjunction with exposure to personalized traumatic scripts immediately followed by active or sham tcVNS and measurement of IL-6 and other biomarkers of inflammation. Patients then self administered active or sham tcVNS twice daily for three months. PTSD symptoms were measured with the PTSD Checklist (PCL) and the Clinician Administered PTSD Scale (CAPS), clinical improvement with the Clinical Global Index (CGI) and anxiety with the Hamilton Anxiety Scale (Ham-A) at baseline and one-month intervals followed by a repeat of measurement of biomarkers with traumatic scripts. After three months patients self treated with twice daily open label active tcVNS for another three months followed by assessment with the CGI. Traumatic scripts increased IL-6 in PTSD patients, an effect that was blocked by tcVNS (p<.05). Active tcVNS treatment for three months resulted in a 31% greater reduction in PTSD symptoms compared to sham treatment as measured by the PCL (p=0.013) as well as hyperarousal symptoms and somatic anxiety measured with the Ham-A p<0.05). IL-6 increased from baseline in sham but not tcVNS. Open label tcVNS resulted in improvements measured with the CGI compared to the sham treatment period p<0.05). These preliminary results suggest that tcVNS reduces inflammatory responses to stress, which may in part underlie beneficial effects on PTSD symptoms.

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Non-invasive Vagal Nerve Stimulation Effects on Hyperarousal and Autonomic State in Patients with Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury: Preliminary Evidence.

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