Project Summary/Abstract Accumulating evidence from studies in rodents suggests that emotional reactions to threatening stimuli rely on neurophysiological changes within an anxiety-processing network that includes the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (vHPC) [1]. Since rodent studies often use laboratory animal models (similar to healthy humans) it is unclear whether findings will translate to the human mPFC-BLA-vHPC network especially in individuals with various levels of anxiety such as post-traumatic stress disorder (PTSD) or generalized anxiety disorder (GAD). The proposed project will implement a first-of-its-kind platform for intracranial electroencephalographic (iEEG) recording and intracranial electrical stimulation (iES) of mPFC-BLA-vHPC oscillatory activity during laboratory and naturalistic fear-based tasks using immersive virtual reality (VR) technology and wearable biometric sensors capable of recording physiology (eye-blinks, heart rate variability [HRV], skin conductance response [SCR], and pupil size). Through an interdisciplinary collaboration between UCLA and the Veteran’s Administration Greater Los Angeles Healthcare System (VAGLAHS) the proposed project will have access to 80 epilepsy participants implanted with mPFC, BLA, and/or vHPC depth electrodes with varying levels of dysregulatory anxiety-related processing. Since our studies address basic questions about the role of mPFC-BLA-vHPC oscillations in human fear and anxiety, the results will bridge findings across species and lay the scientific foundation for helping future patients with debilitating anxiety disorders.