Non-invasive brain stimulation as a tool to study cerebellar-M1 interactions in humans

The recent development of non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) has allowed the non-invasive assessment of cerebellar function in humans. Early studies showed that cerebellar activity, as reflected in the excitability of the dentate-thalamo-cortical pathway, can be assessed with paired stimulation of the cerebellum and the primary motor cortex (M1) (cerebellar inhibition of motor cortex, CBI). Following this, many attempts have been made, using techniques such as repetitive TMS and transcranial electrical stimulation (TES), to modulate the activity of the cerebellum and the dentate-thalamo-cortical output, and measure their impact on M1 activity. The present article reviews literature concerned with the impact of non-invasive stimulation of cerebellum on M1 measures of excitability and "plasticity" in both healthy and clinical populations. The main conclusion from the 27 reviewed articles is that the effects of cerebellar "plasticity" protocols on M1 activity are generally inconsistent. Nevertheless, two measurements showed relatively reproducible effects in healthy individuals: reduced response of M1 to sensorimotor "plasticity" (paired-associative stimulation, PAS) and reduced CBI following repetitive TMS and TES. We discuss current challenges, such as the low power of reviewed studies, variability in stimulation parameters employed and lack of understanding of physiological mechanisms underlying CBI.