146 Intracranial Correlates of Fear Memory in Freely Moving Humans During Virtual Reality

Abstract

INTRODUCTION: Distressing reactions to perceived threats in safe environments is a hallmark feature of anxiety-related disorders such as post-traumatic stress disorder (PTSD) and generalized anxiety disorder (GAD). The development of targeted neural circuit therapies requires an understanding of how neurophysiological activity relates to behavior and subjective emotional experience. METHODS: The task induced memories fear memories, a critical component of anxiety-related disorders etiology, using a novel virtual reality platform. Here, participants freely explored a virtual reality environment via walking or joystick. Participants were instructed to stop movement following color change of the room. When the room turned green (CS+), a noxious virtual reality stimulus (insect) attacked the participant (US) 6 seconds following color change onset. When the room turned blue (CS-), no noxious VR stimulus occurred. In addition to intracranial electroencephalography (iEEG) activity, we recorded physiological and behavioral metrics of fear. RESULTS: We found that the same neural signature indicative of fear memory retrieval in rodents (increased amygdala theta oscillations) was significantly elevated for the fear compared to the neutral cue in freely behaving humans. CONCLUSIONS: These findings represent an important step in translating decades of research in rodents to humans and provide putative electrophysiological signatures of fear behavior that can be used as putative targets for treatment with closed loop brain stimulation therapies. We believe that this combined collection of simultaneous autonomic responses to subjective emotional (fear ratings and physiology), clinical symptoms (anxiety scales) and neural activity has immense transdiagnostic clinical potential for anxiety-related disorders and can inform neurosurgical approaches to treating severe psychopathology.