Hippocampal-Neocortical Interactions During Naturalistic Learning

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PROJECT SUMMARY Episodic memories are representations of our personal past, anchored to time and space. Episodic memory impairments in neurological disorders like epilepsy, traumatic brain injury, and Alzheimer’s Disease significantly limit patients’ ability to work and live independently. In everyday life, the brain must process the continuous present to form discrete memories of the past. This ability to parse experience into meaningful chunks, termed event segmentation, is foundational to human episodic memory. Functional neuroimaging studies suggest that the hippocampus and a posterior cortical network demonstrate a simultaneous increase in activity at event boundaries and endings, but the neural events supporting this demarcation are unknown. Numerous rodent studies suggest that neural oscillations—particularly theta, gamma, and sharp-wave ripple (SWR) activity—coordinate hippocampal-neocortical interactions at these critical junctures. Our long-term goal is to discover how the brain organizes and consolidates continuous experience under naturalistic circumstances. The objective of this proposal is to measure the hippocampal-neocortical dynamics at key moments in episodic memory. Our central hypothesis is that the hippocampus plays a critical role in segmenting and consolidating information delivered from the neocortex, via enhanced theta-gamma activity at event boundaries and increased SWR rate during post-viewing rest. To test these main hypotheses, we will obtain intracranial EEG (iEEG) recordings from epilepsy patients undergoing invasive monitoring for surgical treatment. Subjects will view a series of short films that possess a narrative structure and sequence, then will be asked to recall selected content. Upon successful completion of this project, we will accomplish the following aims: Aim 1. To measure the relative contributions of hippocampus and PMN to event segmentation during film viewing. Aim 2. To measure the hippocampal contribution to memory consolidation during post- viewing rest. Aim 3. To test the necessity of the hippocampus for event segmentation through electrical stimulation (ES). This proposal represents a significant advance from prior work in the cognitive neuroscience of memory by using iEEG to determine the hippocampal-neocortical oscillations involved in remembering naturalistic events. This project is innovative in concept and method because of (1) the use of short films to investigate human episodic memory; (2) the translation of key neurophysiological findings in rodent memory to human episodic memory; and (3) establishing the necessity of the hippocampus in event segmentation and memory performance through ES. Our findings will advance mechanism-guided approaches to the assessment and remediation of memory dysfunction in neuropsychiatric disorders such as epilepsy and traumatic brain injury.