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 as well as 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 yet been established. Here, we recorded intracranial electroencephalography from the hippocampus in 20 epilepsy patients during a MSL task in which participants showed steady improvement across nine 30-second training blocks interspersed with 30-second rest (‘offline’) periods. We first demonstrate that ripple rates strongly increase during rest periods relative to training blocks. Importantly, ripple rates during rest periods tracked learning behaviour, both across blocks and across participants. These results suggest that hippocampal ripples during offline periods play a functional role in motor sequence learning and that the hippocampus may be involved in offline learning beyond episodic memory.