Project Summary/Abstract Episodic memory impairment is a serious challenge for individuals with neurological and psychiatric disorders that impact the hippocampus, including epilepsy, brain injury, neurodegeneration, schizophrenia, and PTSD. The development of effective treatments will require better understanding of brain mechanisms that support memory formation, storage, and retrieval. The goal of this project is to improve such understanding by testing a hypothesis about the role of the human hippocampus and its interactions with large-scale brain networks in memory formation. Episodic memory formation is a temporally extended process whereby individuals actively sample information in the environment via saccadic eye movements (for visual information), bind this information into an evolving memory representation, and then use this memory representation to inform subsequent viewing of information, and so on. Although the necessary role of the hippocampus in episodic memory formation is well established, little is known regarding how it participates in the extended process of memory formation that occurs during active sampling. This represents a knowledge gap in mechanistic understanding of episodic memory formation, as active sampling is the dominant manner in which memories are created. This project tests the role of the human hippocampus in providing online representation of episodic content and providing the top-down signals to brain networks for visuospatial attention and visual processing needed to drive visual sampling for the formation of coherent episodic memories. This hypothesis will be tested in several experiments that measure and manipulate hippocampal activity within eye-tracking tasks designed to isolate the interplay between memory and visual sampling during memory formation. These experiments will be performed in individuals with epilepsy undergoing neurosurgical procedures as part of clinical care, as this provides invasive recordings of neural activity (iEEG) from the hippocampus and other regions of interest with temporal resolution that matches the rapid pace of eye movements. The temporal resolution of iEEG is key to addressing the hypotheses concerning how the hippocampus drives visual sampling, in addition to responding to it. Direct electrical stimulation through the iEEG electrodes will also be used to test the necessary role of hippocampal processing in driving active visual sampling. By rigorously testing the role of hippocampus in interaction with large-scale networks during the process of memory formation that occurs via active sampling, this project aims to better understand mechanisms relevant to the disruptions of memory formation that occur in neurological and psychiatric disorders. These findings could inform technological approaches to treat memory disorders.