Load-dependent amygdala neural representation and amygdala-hippocampus interaction in non-emotional working memory maintenance

Retaining information in working memory (WM) is an active process that requires neural activity within and between regions. The human amygdala (AMY) and hippocampus (HPC) are known to play crucial roles in WM processing. Although electrophysiological studies have revealed that the HPC supports multi-item maintenance in a load-dependent manner, the characteristics of the AMY and the circuit-level mechanisms underlying AMY-HPC interactions remain largely unexplored. To address this knowledge gap, intracranial EEG recordings from the AMY and HPC in nine epileptic patients were employed to evaluate intraregional neural representations and interregional communications during maintenance under different non-emotional WM loads. High load enhanced low-frequency power and intraregional theta-gamma phase-amplitude coupling (PAC) in the AMY and HPC. At the network level, a high load elicited an increase in the strength of the HPC theta phase modulation, which entrains the AMY gamma amplitude. Furthermore, a high load increased AMY-anterior HPC (aHPC) theta phase synchrony and directional connectivity strength from the aHPC to the AMY. Conversely, posterior HPC (pHPC)-AMY synchrony was not affected by load variations. Overall, these findings highlight the importance of the AMY in non-emotional WM tasks and provide new insights into the neurophysiological basis of AMY-HPC interactions during WM maintenance.