Amygdala engages non-emotional multi-item working memory maintenance through amygdala-hippocampus interaction

Abstract

The process of holding information in working memory (WM) is an active one that requires neural activity within and between regions. The human amygdala (AMY) and hippocampus (HPC) are known to play crucial roles in emotional WM processing. Although human electrophysiological studies have made remarkable progress in revealing that HPC supports multi-item maintenance in a load-dependent manner, the characteristics of AMY and the circuit-level mechanisms underpinning AMY-HPC interactions remain largely unexplored. To address this gap in our knowledge, this study employed intracranial EEG recordings from AMY and HPC in nine epileptic patients to evaluate intra-regional neural representations and inter-regional communications during maintenance under different non-emotional WM loads. The results showed that high load enhances low-frequency power and intra-regional theta-gamma phase-amplitude coupling (PAC) in AMY and HPC. On the network level, high load elicits an increase in the strength of the modulation of HPC theta phase entraining AMY gamma amplitude. Furthermore, high load elevates AMY-aHPC theta phase synchrony and directional connectivity strength, with the direction being from anterior HPC (aHPC) to AMY. Conversely, posterior HPC (pHPC)-AMY synchrony is not affected by load variations. Overall, these findings highlight the importance of AMY in non-emotional WM tasks and shed new light on the neurophysiological basis of AMY-HPC interactions during WM maintenance.