The Role of the Cerebellum in Tremor - Evidence from Neuroimaging

Background: Neuroimaging research has played a key role in identifying which cerebral changes are associated with tremor. Here we will focus on the cerebellum, which may drive tremor oscillations, process tremor-related afferents, modulate activity in remote brain regions, or a combination.

Methods: On the 6^th of October 2021, we conducted a PubMed search to select articles providing neuroimaging evidence for cerebellar involvement in essential tremor (ET), Parkinson's disease (PD) tremor, and dystonic tremor (DT).

Results: In ET, tremor-related activity is found in motor areas of the bilateral cerebellum, and altered functional connectivity within and outside the cerebellum correlates with tremor severity. Furthermore, ET is associated with cerebellar atrophy, but also with compensatory structural changes outside the cerebellum (e.g. supplementary motor area). In PD, tremor-related cerebellar activity and increased cerebello-thalamic coupling has been found. Emerging evidence suggests that the cerebellum plays a key role in dopamine-resistant rest tremor and in postural tremor. Cerebellar structural alterations have been identified in PD, but only some relate to tremor. DT is associated with more widespread cerebral networks than other tremor types.

Discussion: In ET, the cerebellum likely acts as an oscillator, potentially due to loss of inhibitory mechanisms. In contrast, in PD the cerebellum may be a modulator, which contributes to tremor oscillations by influencing the thalamo-cortical system. The precise role of the cerebellum in DT remains unclear. We recommend that future research measures tremor-related activity directly by combining electrophysiology with neuroimaging, while brain stimulation techniques may be used to establish causality.

Highlights: This review of neuroimaging studies has provided convincing evidence that the cerebellum plays a key role in the pathophysiology of ET, PD tremor, and dystonic tremor syndromes. This contribution may consist of driving tremor oscillations, processing tremor-related afferents, modulating activity in remote brain regions, or all the above.