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 s typing blocks interspersed with 30 s rest ("offline") periods. We first demonstrated that ripple rates strongly increased during rest relative to typing blocks. Importantly, ripple rates during rest periods tracked behavioral 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.