Ensemble reactivations during brief rest drive fast learning of sequences

Sandon Griffin, Preeya Khanna, Hoseok Choi, Katherina Thiesen, Lisa Novik, Robert J. Morecraft and Karunesh Ganguly ()
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Sandon Griffin: University of California, San Francisco
Preeya Khanna: University of California, San Francisco
Hoseok Choi: University of California, San Francisco
Katherina Thiesen: University of California, Davis
Lisa Novik: University of California, Davis
Robert J. Morecraft: The University of South Dakota
Karunesh Ganguly: University of California, San Francisco

Nature, 2025, vol. 638, issue 8052, 1034-1042

Abstract: Abstract During motor learning, breaks in practice are known to facilitate behavioural optimizations. Although this process has traditionally been studied over long breaks that last hours to days1–6, recent studies in humans have demonstrated that rapid performance gains during early motor sequence learning are most pronounced after very brief breaks lasting seconds to minutes7–10. However, the precise causal neural mechanisms that facilitate performance gains after brief breaks remain poorly understood. Here we recorded neural ensemble activity in the motor cortex of macaques while they performed a visuomotor sequence learning task interspersed with brief breaks. We found that task-related neural cofiring patterns were reactivated during brief breaks. The rate and content of reactivations predicted the magnitude and pattern of subsequent performance gains. Of note, we found that performance gains and reactivations were positively correlated with cortical ripples (80–120 Hz oscillations) but anti-correlated with β bursts (13–30 Hz oscillations), which ultimately dominated breaks after the fast learning phase plateaued. We then applied 20 Hz epidural alternating current stimulation (ACS) to motor cortex, which reduced reactivation rates in a phase-specific and dose-dependent manner. Notably, 20 Hz ACS also eliminated performance gains. Overall, our results indicate that the reactivations of task ensembles during brief breaks are causal drivers of subsequent performance gains. β bursts compete with this process, possibly to support stable performance.

Date: 2025
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DOI: 10.1038/s41586-024-08414-9

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