Sleep ripples drive single-neuron reactivation for human memory consolidation

Abstract Sleep transforms fragile experiences into lasting memories, but the neuronal basis of this process in humans has remained elusive. In rodents, hippocampal ripples orchestrate the replay of place cell sequences, establishing a cellular mechanism for consolidation – though with limited generalizability to human memory. In humans, neuroimaging has revealed large-scale offline reactivation, but these coarse signals leave open whether individual neurons are reactivated and how ripples might mediate this process. Here, we bridge this gap by directly recording 1,466 medial temporal lobe (MTL) neurons and intracranial electroencephalography during learning, post-learning wakefulness, and sleep. We show that ripples robustly drive neuronal firing, with sleep ripples eliciting stronger activation than wake ripples. Critically, neurons tuned to items that were later remembered fired more strongly during ripples than those coding for forgotten items, and this memory-linked reactivation was selectively observed during sleep. Finally, ripple-associated neuronal MTL bursts were detectable across widespread cortical activity, pointing to a mechanism for systems-level consolidation. Together, these findings provide the first direct evidence that ripple-driven single-neuron reactivation supports human episodic memory consolidation and reveal why sleep — compared to wakefulness — offers a privileged window for stabilizing memories. Competing Interest Statement The authors have declared no competing interest.