Project Summary/Abstract How does memory guide our choices in particular locations and contexts? How does our brain accomplish this? Memory, navigation, and context dependent decision-making are essential for adaptive human behavior and are impaired in several neurological and psychiatric disorders. This proposal aims to identify the basic mechanisms mediating context dependent memory representations in the human brain towards advancing refined therapeutic tools for memory enhancement in clinical populations. More specifically, this proposal will investigate the neural basis of context dependent memory encoding and retrieval, behavior that enables us to flexibly act in the world according to particular situations. Influential human brain imaging and lesion studies have identified that the hippocampus (HPC) and the medial prefrontal cortex (mPFC), along with their interactions, are where memory and navigational computations take place. However, these studies have poor temporal resolution and do not directly measure electrical activity. Thus, we don't understand how context dependent memories are formed and retrieved in humans. The proposed experiments will utilize direct human brain recordings from HPC and mPFC in epilepsy patients undergoing invasive seizure monitoring to yield new insight into the electrophysiological basis of human memory. Patients perform a context dependent learning and memory task in which objects are associated with different rewards depending on context. The task is embedded in a virtual environment, enabling comparisons of neural signatures of both spatial navigation and associative memory. We hypothesize that synchronous, “phase coded” oscillatory activity within and between the HPC and mPFC supports context dependent memory. Aiming to identify the unique and overlapping electrophysiological mechanisms mediating context dependent representations, this proposal is likely to transform our understanding of how the human brain coordinates its activity in the service of adaptive human behavior. This work will also shed new light on how the human brain utilizes complex, context dependent associations to provide insight into putative mechanisms mediating impairments in several clinical populations.