Time-Dependent Enhancement of Motor Dexterity and Cerebellar Function via Premotor-Cerebellar Associative Stimulation

Paired associative stimulation (PAS) techniques are key to understanding neuromodulation and plasticity. Because of the tight interconnections between the cerebral and cerebellar cortices, noninvasive cerebro-cerebellar associative stimulation may enhance cerebellar function; however, this has not been studied in humans. This study investigated whether PAS of the cerebellar hemisphere and premotor cortex (PMC) modulates human cerebellar function in a time-dependent manner. The inclusion criteria were as follows: right-handedness and no history of brain disease. Cerebellar-target PAS was performed by repeating paired stimuli on the left cerebellar hemisphere preceded by the right PMC using interstimulus intervals (ISI) of 5, 20, or 40 ms on three different days. Cerebellar brain inhibition (CBI) and motor dexterity (9-Hole Peg Test and line-tracing tests using the left hand) were evaluated. Twenty-three healthy volunteers aged 20-29 years participated in this study. The CBI of the left cerebellum showed significant enhancement after cerebellar-target PAS with an ISI of 20 ms (CBI-3, p = 0.0031; CBI-5, p = 0.0006; and CBI-10, p = 0.0052) and a significant decrease after an ISI of 5 ms. The performance time on the 9-Hole Peg Test and line tracing tests decreased after an ISI of 20 ms and increased after an ISI of 5 ms. Cerebellar-target PAS with an ISI of 20 ms targeting the left cerebellum improved motor dexterity in the left hand. The effects of cerebellar-target PAS depend on the stimulation interval, which could be a potential therapeutic approach for the neurorehabilitation of patients with cerebellar disorders. Study Registration: jRCT1052210071.