Sharp-wave ripples transmit hippocampal to neocortical information: A human single-neuron study

Memory consolidation is assumed to rely on fine-tuned communication within and between hippocampal and cortical neuronal circuits during offline brain states. Sharp-wave ripples (SWRs) have been proposed as the pivotal signature for consolidation, triggering hippocampal replay and information transfer to cortical sites. Critically, although SWRs are precisely coupled to the cardinal NREM sleep-related mesoscopic brain rhythms (i.e., cortical slow oscillations and thalamo-cortical spindles), evidence for a link between SWRs and directed information transfer is scarce. Here, we leveraged the rare opportunity of nocturnal single-unit and LFP recordings in neurosurgical patients to uncover the SWR-triggered information flow by tracking the impact of SWRs on single-neuron activity along the hippocampal output network including entorhinal and parahippocampal cortex. We recorded 1433 neurons during 40 night sessions in 17 epilepsy patients implanted with hybrid macro-micro electrodes for presurgical diagnostics. Preliminary results indicate a consistent pattern of temporally precise increases in neuronal firing rate (FR) synchronized with hippocampal SWRs. Importantly, FR increases were not confined to local hippocampal neurons but also became apparent in single neurons in distant, downstream regions, suggesting an interregional impact of SWRs. The temporal delay along the hippocampal-neocortical pathway suggests a causal directionality, with the hippocampus as the driving hub. Our results support the idea of a causal relationship between SWRs and hippocampal-neocortical information transmission during sleep. SWRs appear to trigger a cascade of temporally precise, interregional synchronized co-firing, facilitating synaptic modifications and thus underpinning their essential mechanistic role within systems consolidation.