Hippocampal ripples during offline periods predict human motor sequence learning.

High-frequency bursts in the hippocampus, known as ripples (80-120 Hz in humans), have been shown to support episodic memory processes. However, converging recent evidence in rodent models and human neuroimaging suggests that the hippocampus may be involved in a wider range of memory domains, including motor sequence learning (MSL). Nevertheless, no direct link between hippocampal ripples and MSL has been established yet. Here, we recorded intracranial electroencephalography (iEEG) from the hippocampus in 20 epilepsy patients (11 males and 9 females) during an MSL task in which participants showed steady improvement across nine 30-second typing blocks interspersed with 30-second rest ('offline') periods. We first demonstrated that ripple rates strongly increased during rest relative to typing blocks. Importantly, ripple rates during rest periods tracked behavioural improvements, both across learning blocks and across participants. These findings suggest that hippocampal ripples during rest periods play a role in facilitating motor sequence learning.Significance Statement This study provides the first direct evidence that hippocampal ripples, brief high-frequency oscillations previously linked to episodic memory, also play a role in human motor sequence learning. By recording intracranial EEG from epilepsy patients during a motor learning task, we found that ripple rates increased during rest periods between typing blocks and closely tracked behavioural improvements in performance. These findings suggest that hippocampal ripples during offline periods may facilitate consolidation of newly acquired motor skills, extending the functional significance of ripples beyond episodic memory.