Search

ObjectiveExacerbated autonomic responses to acute stress are prevalent in posttraumatic stress disorder (PTSD). The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on autonomic responses to acute stress in patients with PTSD. The authors hypothesized tcVNS would reduce the sympathetic response to stress compared to a sham device.MethodsUsing a randomized double-blind approach, we studied the effects of tcVNS on physiological responses to stress in patients with PTSD (n=25) using noninvasive sensing modalities. Participants received either sham or active tcVNS after exposure to acute personalized traumatic script stress and mental stress (public speech, mental arithmetic) over a three-day protocol. Physiological parameters related to sympathetic responses to stress were investigated.ResultsRelative to sham, tcVNS paired to traumatic script stress decreased sympathetic function as measured by: decreased heart rate (adjusted ß=-5.7%; 95% CI: ±3.6%, effect size d=0.43, pConclusiontcVNS attenuates sympathetic arousal associated with stress related to traumatic memories as well as mental stress in patients with PTSD, with effects persisting throughout multiple traumatic stress and stimulation testing days. These findings show that tcVNS has beneficial effects on the underlying neurophysiology of PTSD. Such autonomic metrics may also be evaluated in daily life settings in tandem with tcVNS therapy to provide closed-loop delivery and measure efficacy.ClinicalTrials.gov Registration # NCT02992899HighlightsWe studied the effects of tcVNS on physiological responses to stress in patients posttraumatic stress disorder (PTSD).tcVNS modulates physiologic reactivity to traumatic and mental stress in PTSD, and modulates autonomic tone when applied without acute stress.Repeated tcVNS enhances resilience in the face of repeated stress in PTSD as quantified by peripheral autonomic measures which potentially could serve as real-time measures to evaluate the therapy response in longitudinal settings.

Transcutaneous cervical vagal nerve stimulation (tcVNS) devices are attractive alternatives to surgical implants, and can be applied for a number of conditions in ambulatory settings, including stress-related neuropsychiatric disorders. Transferring tcVNS technologies to at-home settings brings challenges associated with the assessment of therapy response. The ability to accurately detect whether tcVNS has been effectively delivered in a remote setting such as the home has never been investigated. We designed and conducted a study in which 12 human subjects received active tcVNS and 14 received sham stimulation in tandem with traumatic stress, and measured continuous cardiopulmonary signals including the electrocardiogram (ECG), photoplethysmogram (PPG), seismocardiogram (SCG), and respiratory effort (RSP). We extracted physiological parameters related to autonomic nervous system activity, and created a feature set from these parameters to: 1) detect active (vs. sham) tcVNS stimulation presence with machine learning methods, and 2) determine which sensing modalities and features provide the most salient markers of tcVNS-based changes in physiological signals. Heart rate (ECG), vasomotor activity (PPG), and pulse arrival time (ECG+PPG) provided sufficient information to determine target engagement (compared to sham) in addition to other combinations of sensors. resulting in 96% accuracy, precision, and recall with a receiver operator characteristics area of 0.96. Two commonly utilized sensing modalities (ECG and PPG) that are suitable for home use can provide useful information on therapy response for tcVNS. The methods presented herein could be deployed in wearable devices to quantify adherence for at-home use of tcVNS technologies.