Essential tremor, the olivocerebellar system and motor timing – An fMRI study

Abstract

Background Essential tremor (ET) is the most common tremor disorder. It has been repeatedly shown that the olivocerebellar system is involved in ET, consisting of the inferior olive nucleus (ION), dentate nucleus (DN) and cerebellar cortex. Impairment of the central timing mechanism in ET has been suggested. The olivocerebellar system plays an important role in motor timing. In order to study the functional involvement of this system in ET, we employed a task involving motor timing during functional MRI (fMRI). Methods Thirty propranolol sensitive ET patients with familial upper limb tremor and 30 healthy controls were included. T2 ∗ -weighted EPI sequences were acquired (180 volumes, TR: 2s, voxel size: 3.5 × 3.5 × 3.5 mm, 3TMRI). The task consisted of alternating rest and finger tapping (rate of 2 Hz) blocks. Task performance was measured by electromyography. Analysis was performed in SPM8 (standard preprocessing, normalization according to the spatially unbiased infra-tentorial template, 4 mm smoothing kernel). The left ION was localized with a conjunction analysis of patients and controls. For this abstract, quantified tapping performance is not yet incorporated. Results Within-group random-effects analysis restricted to the brainstem and cerebellum showed activations throughout the cerebellum (bilateral lobules V, VI, VIIIA) and in both left and right ION. Preliminary between-group analysis of the ION and CB right lobule VI showed significantly higher activations in controls compared to ET patients. Conclusions Exploratory analysis suggests altered activity in the olivocerebellar system in ET patients compared to controls during a motor timing task. Inclusion of task performance and effective connectivity analysis will be carried out to aid us in discriminating between altered activity due to task performance and pathological motor timing related to ET. Understanding the role of the olivocerebellar system in ET is of great importance for unraveling the mechanism of tremor genesis.