Leveraging Longitudinal DBS Recordings to Probe Pharmacological Mechanisms: Investigating the Role of Orexin Antagonists on Extended Amygdala Activity.

Advances in deep brain stimulation (DBS) technology now allow electrophysiological signals to be recorded from implanted electrodes in addition to providing stimulation. These intracranial recordings provide a rare opportunity to measure brain activity in human subjects over time in relation to symptoms and naturalistic behaviors. Objective biomarkers can be used to identify the circuit-level mechanisms of action of treatment interventions, such as pharmacological agents, in human subjects. Here, the authors describe methods for conducting long-term electrophysiological recordings in naturalistic settings during pharmacological interventions to characterize the neural effects of psychotropic medications. The authors present an illustrative case of a patient receiving DBS for their severe, refractory OCD with co-morbid insomnia in which beta activity was being longitudinally monitored from the bed nucleus of the stria terminalis (BNST). The authors find that dose reductions of a sleep-promoting orexin antagonist for insomnia, taken at night, significantly elevated the BNST beta biomarker of arousal overnight. This case study demonstrates a role for orexin signaling in regulating arousal-related BNST activity and highlights the utility of DBS recordings for identifying circuit-based mechanisms of action of pharmacologic agents.