Theta-Gamma Phase-Amplitude Coupling Supports Working Memory Performance in the Human Hippocampus

Abstract Phase-amplitude coupling (PAC) occurs in the human hippocampus during working memory and supports the contribution of the hippocampus in the maintenance of multiple items. Additionally, PAC has the potential to reveal the neural mechanisms underlying multi-item maintenance in the hippocampus by providing a putative architecture for multi-item representation. Theta and gamma range rhythms are prominent neuronal oscillations in the hippocampus. Studies on the role of theta frequency oscillation in local field potentials in human memory have shown mixed evidence for successful remembering. The role of gamma oscillatory activity in contributing to memory retrieval is not yet fully understood. They also interact with each other in the form of PAC during memory performance. This study aims to investigate the neurophysiological function of theta-gamma PAC in the human hippocampus during a multi-item working memory task and characterize its association with performance. Theta-gamma cross-coupling investigation in the electrocorticographic signals was performed from the hippocampus recording of ten epilepsy patients while they were engaged with the working memory task. The results show strong correlations between PAC levels and the subjects memory performance, but no correlation with theta and gamma power individually, specifically in the retrieval phase of a working memory task. These observations demonstrate the possible role of PAC in memory-related operations, suggesting a PAC-based neural mechanism for working memory in the hippocampus. Significance Statement The findings from this study elucidate the crucial role of phase-amplitude coupling in the human hippocampus during working memory tasks, specifically in the maintenance of multiple items. By analyzing electrocorticographic recordings from epilepsy patients engaged in a working memory task, our research unveils a direct correlation between PAC levels and memory performance during the retrieval phase, which is not observed when analyzing theta and gamma oscillations individually. These findings suggest a theta-gamma coupling based mechanism within the hippocampus that facilitates working memory, offering new insights into the complex neural processes underlying memory encoding and retrieval. This advancement in understanding the neural architecture of memory not only contributes to the foundational knowledge of cognitive neuroscience but also opens avenues for developing targeted interventions for enhancing memory performance with translational application in treating memory-related neurological disorders.