Novel Technologies for the Diagnosis and Treatment of Posttraumatic Stress Disorder

The brain and the heart share an active and reciprocal dialogue, continuously modulating each other's function. For individuals who have experienced traumatic events, the reminders of these events affect both the brain and heart due to this intimate relationship, and can later develop into posttraumatic stress disorder (PTSD) due to the repeated activation of trauma-related neuropathways and autonomic imbalance. Electrical stimulation of the vagus nerve —the longest cranial nerve, which regulates the autonomic state—using an implantable device is a potential treatment method to address such imbalance. Noninvasive vagal nerve stimulation (nVNS) devices offer inexpensive and low-risk alternatives to surgical implants, but their effects on the physiology are not well understood. Real-time, noninvasively obtained biomarkers are required to tailor therapy and to close the loop for automated delivery. This dissertation focuses on identifying and developing noninvasive technologies for nVNS in the context of PTSD. Identification of noninvasive measures that can diagnose and treat PTSD is imperative for at-home usage and for developing closed-loop systems. This research first focuses on how noninvasive sensing modalities could be instrumented and used in conjunction with signal processing and machine learning methods to quantify an individual’s autonomic state. Second, a mechanistic, sham-controlled, randomized, double blind study on the use of nVNS for dampening stress response is investigated in multiple dimensions: downstream physiological effects and biochemical biomarkers, with a particular focus on real-time physiological biomarkers and their potential for closing the loop for machine learning guided personalized neuromodulation. The broader impacts of this research cover accessible, low-cost diagnosis and treatment options for patients with stress-related neuropsychiatric disorders, which are important public health problems and projected to increase due to COVID-19 pandemic. The sensing modalities, algorithms, biomarkers, and methodologies detailed in this dissertation lay the groundwork for future efforts to objectively diagnose and treat neuropsychiatric disorders remotely, outside of clinical settings.Ph.D