Non-invasive temporal interference stimulation targeting the hippocampus enhances fast motor memory consolidation

Converging neuroimaging evidence indicates that the hippocampus is involved in motor sequence learning (MSL) and its consolidation at multiple timescales. However, direct evidence for a causal role of the hippocampus in these processes in healthy humans remains scarce, partly due to the inability of conventional non-invasive brain stimulation techniques to reach this deep brain structure. Here, we used temporal interference stimulation (TIS) - a technique enabling non-invasive stimulation targeted toward deep brain regions - to probe the functional role of the hippocampus in MSL and its consolidation. In two separate experiments, sixty-four young healthy adults (36 females) received, in within-subject counterbalanced designs, active (5 Hz envelope) or control (0 Hz envelope) hippocampal-targeted TIS either during active practice of an MSL task (task-TIS experiment, n = 32) or during the short rest periods interleaved with task practice known to support rapid forms of consolidation (rest-TIS experiment, n = 32). Consolidation was assessed at both the micro timescale (i.e., over the short "micro-offline" rest intervals interspersed with task practice) and macro timescale (i.e., over a 24-hour "macro-offline" retention interval). Our results indicate that TIS targeting the hippocampus during inter-practice rest periods - but not during task practice - significantly enhanced micro-offline gains in performance as compared to control stimulation. While this effect did not carry over to the 24-hour retention interval at the group level, participants with greater stimulation-induced micro-offline gains showed larger overnight performance improvements. These findings provide the first direct evidence that experimental interventions targeting the hippocampus modulate offline motor memory consolidation processes.