Modeling Latent Dynamics of the Autonomic Nervous System in Response to Trauma Recall and Non-Invasive Vagus Nerve Stimulation

Objective: To develop a person-specific dynamic modeling approach to quantify the time course of multiple peripheral markers of the autonomic nervous system (ANS) in response to acute stressors and potential stress-reducing interventions. Methods: We curated data (N=50 participants) from a double-blind, randomized, sham-controlled trial of non-invasive vagus nerve stimulation (nVNS) for posttraumatic stress disorder (PTSD). For each participant, a multi-input, multi-output, linear state space model (SSM) was trained on $\sim$3500 s of cardiovascular and respiratory marker time series data and tested for predictive validity on $\sim$2000 s of held-out data. The inputs to each SSM indicated the presence or absence of potential stressors (e.g., traumatic memories) and interventions (e.g., nVNS or sham stimulation). We analyzed the SSMs' step responses to each input and compared the responses to real data. We then simulated the effects of just-in-time nVNS delivered during a traumatic memory. Results: The SSMs outperformed baseline forecasting methods on held-out data (P$< $.05). Responses to nVNS were in the opposite direction of responses to traumatic memories, with neutral conditions (included for comparison) remaining in between. For participants with PTSD, just-in-time nVNS attenuated–and briefly reversed–the response to traumatic memories along the principal axis of variance, which explained $\sim$50% or more variance and mirrored expected ANS changes. Just-in-time sham stimulation produced no attenuation. Conclusion: Our methods capture latent ANS dynamics during increasing and decreasing stress levels associated with traumatic memories and nVNS, respectively. Significance: Traumatic memories can cause pathological stress responses during daily life that just-in-time non-invasive neuromodulation may potentially help mitigate.