Understanding and modulating paroxysmal sympathetic hyperactivity (PSH) after traumatic brain injury (TBI): A neuroimaging and physiologic data analytic approach

Traumatic brain injury (TBI) is a significant public health issue with high morbidity and mortality, yet few proven management strategies exist for hospitalized patients. Up to 40% of critically ill acute TBI patients experience paroxysmal sympathetic hyperactivity (PSH), marked by recurrent episodes of tachycardia, tachypnea, hypertension, hyperthermia, motor posturing, and diaphoresis. PSH contributes to secondary injury, complications, and worse outcomes in affected patients. Despite the introduction of an expert-consensus based PSH-Assessment Measure (PSH-AM), clinical recognition is difficult, and medication-based symptom management is not evidence-based and may cause harm. There is a critical need for objective tools to detect and monitor symptoms and to develop mechanistically-guided effective treatments with fewer side effects. My preliminary work provides proof of concept for an objective PSH physiologic index based on continuous vital sign data, which may overcome limitations of the PSH-AM. Additionally, my preliminary neuroimaging work suggests that structural injury to fronto-limbic components of the central autonomic network (CAN) conveys risk for PSH. Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging non-invasive portable device-based therapy that modulates the CAN, reduces sympathetic outflow, and improves sympathetic- parasympathetic balance. My overall objective is to build on this foundation to develop automated tools enabling goal-directed taVNS neuromodulation for post-TBI PSH. I hypothesize that TBI-induced fronto-limbic damage predisposes to measurable physiologic changes reflecting sympathetic-parasympathetic imbalance, which can be safely modulated by non-invasive taVNS. To test this hypothesis, I propose the following specific aims: 1) refine an automated PSH physiologic index; 2) define the structural and functional neural network correlates of PSH; and 3) evaluate the physiologic effects of taVNS in acute TBI. The successful completion of these aims will generate fundamental mechanistic knowledge and identify practical tools for post-TBI PSH targeted management, crucial steps toward personalized, goal-directed therapy for an important contributor to TBI morbidity and mortality. My work will benefit from a team of expert mentors with unique, complementary skillsets, who will train me in physiologic data analysis, advanced neuroimaging research methods, and TBI clinical trial design and implementation. A K23 award will support my long-term professional goal to become an independent investigator utilizing multimodal data to target critically ill TBI patients for neuromodulatory interventions that alter disease trajectory and improve recovery. If successful, this work will directly lead to an R01 investigating the efficacy of taVNS to reduce physiologic manifestations of PSH, promote long-term adaptive central autonomic network functional connectivity, and improve TBI outcomes in appropriately targeted patients. Project Number: 1K23NS149188-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Jamie Podell | Institution: UNIVERSITY OF MARYLAND BALTIMORE, BALTIMORE, MD | Award Amount: $228,641 | Activity Code: K23 | Study Section: Special Emphasis Panel[ZRG1 NINC-Q (01)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11357915