Direct interactions between the human insula and hippocampus during memory encoding

The hippocampus is critical for encoding episodic memories, but how it interacts with cortical regions during this process remains unclear. In this study, 16 participants with implanted electrodes in the insula (217 sites) and hippocampus (131 sites) viewed emotionally valenced words and attempted to recall them. During encoding, one subset of insular neuronal populations showed changes in aperiodic activity that predicted successful recall. These insular changes followed hippocampal theta but preceded hippocampal ripples. Another subset of insular sites responded to word valence, unrelated to memory performance. Direct electrical stimulation of memory-related insular sites evoked early responses in the ipsilateral hippocampus, whereas stimulation of valence-related sites did not. Conversely, stimulating hippocampal sites produced slow, variable signals across all insular sites, suggesting asymmetric communication between the hippocampus and the insula. These findings provide a glimpse of mesoscale hippocampal interactions with functionally selective neuronal populations within a given cortical structure.