DOI: 10.1126/sciadv.aeb3579 ISSN: 2375-2548

Elevating cerebellar theta oscillations boosts noninvasively induced motor plasticity

Danny Adrian Spampinato, Valentina Pezzopane, Alex Martino Cinnera, Annibale Antonioni, Elisa Dolfini, Lucia Mencarelli, Matteo Ferraresi, Katia Botta, Andrea Casarotto, Sofia Straudi, Luciano Fadiga, Giacomo Koch

Matching brain stimulation to the brain’s natural rhythms can drive plasticity, yet this principle has rarely been tested in humans. We targeted the cerebellum, a key hub for motor coordination and learning, using a rhythm-tuned protocol that pairs theta-frequency transcranial alternating current stimulation with intermittent theta-burst stimulation to engage plasticity of cerebello-cortical circuits. In young healthy adults, this pairing enhanced fine motor control and hand dexterity, with gains closely tracking physiological markers of cerebellar-driven plasticity. Applying the same approach in chronic stroke survivors yielded parallel behavioral and neural gains, demonstrating preserved rhythm-plasticity coupling despite injury. Control experiments confirmed both frequency specificity and site specificity, underscoring the mechanistic precision of the intervention. By linking theta-frequency cerebellar stimulation to circuit-level and functional outcomes, these findings establish a biologically grounded framework for targeted neurorehabilitation. Rhythm-specific cerebellar stimulation provides a scalable strategy for enhancing plasticity and improving motor function across movement disorders and motor impairments.

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