Non-invasive VNS Effects on Hyperarousal and Autonomic State in Patients with PTSD

Updated: Nov 21, 2019

Journal: Frontiers in Medicine (2017)

Authors: Damon G. Lamb, Eric C. Porges, Greg F. Lewis and John B. Williamson

Background: 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.

Objective: To evaluate the impact of tVNS on indices of hyperarousal including vagal tone, as measured by high frequency HRV, and sympathetic nervous system activity in response to emotionally modulated startle as measured by electrodermal activity.

Methods: Participants were randomized into either tVNS or sham (stimulus calibration only) subgroups and were then given a series of assessments of ANS function including emotionally modulated startle and postural HRV assessments. All participants were fitted with custom tVNS electrodes and had comfort threshold calibration, but stimulus amplitude was set to 0 (sham) or 80% of threshold (tVNS) for the remainder of each participant’s session as pre-assigned by randomization.

Results: Mean RSA was higher with tVNS than sham across all three postural positions (see Figure ​Figure2)2) indicative of increased parasympathetic activity [tVNS effect, F(1, 17) = 3.33, estimated Cohen’s d = 0.88]. Diagnosis groups were pooled for this analysis due to insufficient sample size per cell for the full design and the primacy of the question of tVNS efficacy. This finding is consistent with prior reports of increased HRV with tVNS stimulation (32) in healthy populations.

Conclusions: To our knowledge, no studies have been published showing influence of tVNS treatment on alterations of baseline and emotionally modulated autonomic responses in individuals with PTSD. The results of the current preliminary study are promising and should be replicated and extended. What we observed in the current study is a baseline shift in physiological state, i.e., increased markers of parasympathetic nervous system activity. This change in parasympathetic nervous system activity may be interpreted as evidence of a tamping-down of defensive autonomic response and increased amenability to social engagement (45). Further supporting this interpretation, we observed decreased sympathetic nervous system response to emotionally modulated startle. One might conceptualize tVNS as a prosthetic for prefrontal action in inhibiting limbic activity and shifting emotional state to a more socially adaptive form. Autonomic behavior is central to symptoms of PTSD and effective modulation of these systems is associated with better emotional and health outcomes. Thus, further study of tVNS as a potential treatment or adjuvant for patients with emotional dysregulation in the continuum of PTSD is warranted. Follow-up mechanistic work is necessary for delivery impact and optimization and longitudinal effects the symptom clusters of PTSD as well as tolerability and other factors necessary for realization of this tool as a viable treatment approach. In addition to short-term impacts on emotional/autonomic features of PTSD as assessed in the present investigation, tVNS may also have long-term utility with repeated application in reducing symptoms of PTSD

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