Objective: To assess functional brain network architecture in participants with medically-refractory essential tremor (ET) and to correlate the strength of these networks with clinical tremor severity and response to thalamic deep brain stimulation (DBS).

Background: ET is the most common movement disorder in adults, yet its pathophysiology is poorly understood. Neuroimaging during task-activation states has implicated cerebello-thalamo-cortical pathways in the mechanism of ET but may reflect brain responses to unwanted movements rather than primary pathophysiology. We used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to limit these movement-related confounds on interpretation of functional brain networks in participants with medically-refractory ET.

Method: Participants with ET, scheduled to receive DBS, underwent resting-state scans (3 BOLD 7.3 min runs). Tremor severity was assessed pre- and post-operatively at optimal DBS settings. Scans of age- and sex-matched healthy controls were previously collected. Rigorous preprocessing was performed to minimize the effect of head motion during scan acquisition. Seed regions were applied across the cortex, subcortex, and cerebellum to comprehensively sample the whole brain. Connectomes were obtained by correlating average time courses for each seed pair and compared across groups using object-oriented data analysis. Network-level functional connectivity (FC) was assessed using composite FC scores (mean cross-correlation between nodes). A seed correlation map was computed between a motor thalamus seed and all brain voxels to assess regional FC.

Results: We obtained rs-fcMRI scans in 21 participants with ET and 34 control participants. Connectome structure differed significantly between the ET and control groups. Post-hoc tests of select network-level FC revealed decreased thalamo-somatomotor, thalamo-visual, and auditory-visual FC, increased motor thalamus FC in primary motor cortex, and decreased occipito-parietal and cerebellar FC in ET versus controls. Network FC measures did not correlate with tremor.

Conclusion: Connectome, network, and regional FC data implicate cerebello-thalamo-motor pathway dysfunction in ET. Thalamic and visual networks show the greatest FC differences, suggesting asynchrony of visual feedback and motor networks in ET.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/large-scale-network-changes-in-the-pathophysiology-of-essential-tremor/