Ultrasonic Neuromodulation of the Human Hippocampus Reveals a Causal Role in Rapid Motor Memory Consolidation
Maria Paz Montenegro, Shancheng Bao, Sapna Bisht, Kenneth L. Hoyt, Huiliang Wang, David L. Wright, John J. Buchanan, Yuming Lei
2025 · 10.64898/2025.12.10.693529
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.
Abstract via europepmc.
Exposures
Exposure 1: Hippocampal TUS (posterior hippocampus contralateral to task hand)
Target: hippocampus — “posterior hippocampus”
Device: Sonic Concepts · Sonic Concepts · DPX-500-4CH-008 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | 1,030 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 35 | ✓?⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 360 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 4.3 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
20-ms ultrasound bursts delivered at 5 Hz for 80 s (400 bursts total), corresponding to a 10% duty cycle; delivered once before the motor sequence task.
Exposure 2: M1 validation TUS
Target: primary motor cortex — “primary motor cortex (M1)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · CTX-500-4CH-082 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | ⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
20-ms ultrasound bursts delivered at 5 Hz for 80 s (400 bursts total), corresponding to a 10% duty cycle; delivered once before the motor sequence task.
Flags from extraction
exposures[0].free_field.isppa_w_cm2— 35 W/cm2 is a 'target' Isppa for which peak pressure was measured in a water tank (1.03 MPa); mean delivered Isppa across participants was 35.9 +/- 7.7 W/cm2.exposures[0].in_situ.pressure_kpa— Simulated in situ mean (0.36 +/- 0.003 MPa) across participants, from k-Plan simulations on pseudo-CT.exposures[1].timing.pulse_duration_ms— Paper states all sonication parameters were identical between M1 and hippocampal protocols; values copied from the single protocol description.exposures[1].free_field.pressure_kpa— No pressure or intensity stated for the M1 experiment.exposures[0].timing.pulse_duration_ms— '20-ms bursts at 5 Hz, 10% duty cycle': 20 ms matches duty cycle / PRF, so burst taken as the pulse.n_subjects— 72 includes sham participants; cohorts overlap partly across experiments (52 original plus 20 replication).blinding— Blinding not mentioned in the text.