248 Exploring the Neural Mechanisms of Human Working Memory: An Approach Based on Phase-Amplitude Coupling

INTRODUCTION: Hippocampal phase-amplitude coupling (PAC) occurs during working memory, and prior studies have suggested its utility in supporting multi-item representation. Notably, theta and gamma rhythms are the prominent neuronal oscillations in the hippocampus. However, studies on the role of theta frequency oscillations in human memory have shown mixed evidence for successful encoding and retrieval. Furthermore, the role of gamma oscillatory activity in contributing to memory retrieval is not yet fully understood. These rhythms also interact with each other in the form of PAC during memory-related performance. METHODS: Ten epilepsy patients undergoing hippocampal stereo-EEG depth electrode monitoring performed a visual memory task involving a sequence of images. Memory performance and relation to electrocortigraphic signals was analyzed to determine electrographic predictors of memory retrieval. RESULTS: Contrary to previous studies that linked memory performance primarily with theta power, our findings indicate a significant correlation between PAC—specifically the coupling of theta-phase to gamma amplitude—and the accuracy of memory retrieval. CONCLUSIONS: Theta-gamma coupling appears to be a crucial mechanism within the hippocampus for enhancing working memory capabilities. This discovery not only advances our understanding of the complex neural processes involved in memory encoding and retrieval but also suggests a potential biomarker for targeted interventions in neurological disorders impacting memory.