Ultrasonic Neuromodulation of the Human Hippocampus Reveals a Causal Role in Rapid Motor Memory Consolidation

Abstract

How humans acquire motor skills is a fundamental biological question. Early learning involves rapid gains during practice and brief rest, yet the causal contribution of the hippocampus remains unclear. Here, we applied individualized, MRI-guided transcranial ultrasound stimulation (TUS) to modulate the posterior hippocampus in healthy adults. To establish a physiological benchmark, we first showed that this TUS protocol produced a sustained reduction in corticospinal excitability when applied to the primary motor cortex. When applied to the posterior hippocampus, electroencephalography revealed reduced frontocentral gamma-band activity, providing physiological evidence of hippocampal-frontal network modulation. Behaviorally, TUS altered the temporal dynamics of skill acquisition. Compared with sham, hippocampal TUS attenuated micro-offline gains during rest while increasing performance improvements during active practice. This shift from offline to online learning was replicated in an independent cohort with comparable baseline motor performance. Importantly, hippocampal TUS enhanced overall performance during learning, and this higher level of performance remained evident 24 hours later. Together, these findings provide causal evidence that the human hippocampus contributes to how motor learning is distributed between active practice and brief rest, showing that this temporal organization of learning can be altered by non-invasive neuromodulation.