This study explores the feasibility of modulating cerebellar activity using low-intensity focused ultrasound (LIFUS) in humans.

The cerebellum has extensive connections to cortical structures such as the primary motor cortex (M1). Although established non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can target the cerebellum, they lack the spatial focality to allow detailed investigations of the cerebello-cortical networks. Low intensity focused ultrasound (LIFUS) is a novel stimulation technique that uses acoustic waves above 20 KHz to alter neuronal excitability. LIFUS is capable of reaching deeper brain structures with greater focal width (2-4 mm) compared to TMS and tDCS. This makes LIFUS particularly well-suited to target portions of the cerebellum.

Using a paired LIFUS-TMS paradigm, we compared the effects of different cerebellar LIFUS (cbLIFUS) sonication durations on M1 excitability in healthy human subjects. The cerebellum was sonicated for a duration of 500 ms. Motor-evoked potential (MEP) amplitudes were measured pre-sonication (150 ms before), during sonications (150ms, 300ms, and 450 ms after the start of sonication) and post-sonication (150 ms after the completion of sonication). We also compared the effects of cbLIFUS to cerebellar TMS. 

Preliminary results in four subjects show that 300 ms and 450 ms of cbLIFUS resulted in inhibition of contralateral M1 excitability. However, the largest inhibition was observed at 150 ms post-sonication. When compared to cerebellar TMS, larger inhibition was observed with cbLIFUS at 300ms, 450 ms and post-sonication. The study is ongoing and more subjects are being recruited.

cbLIFUS is a safe option for cerebellar modulation in humans. In particular, cbLIFUS achieved greater M1 inhibition than cbTMS. These effects increased with sonication duration and appear to continue shortly after sonication ended.