Thalamic and Visual Network Dysfunction Relates to Tremor Response in Thalamic Deep Brain Stimulation

Essential tremor (ET) is the most common movement disorder in adults, but its pathogenesis is incompletely understood. Deep brain stimulation of the ventral intermediate thalamic nucleus (VIM DBS) provides effective treatment for medically-refractory cases. We aimed to determine how pre-surgical resting-state functional connectivity (FC) in medically-refractory ET relates to VIM DBS clinical response.

We analyzed resting-state FC MRI in 21 participants with medically-refractory ET who subsequently underwent VIM DBS and 34 matched controls. We applied rigorous quality assurance to minimize motion artifact. Whole-brain correlation matrices were computed across 300 cortical, subcortical, and cerebellar regions and compared across groups using object-oriented data analysis, a powerful novel approach. We used multiple linear regression to determine whether network FC (calculated as mean cross-correlation between nodes) in defined networks predicts VIM DBS response. We assessed regional FC using a seed in motor thalamus.

Whole-brain correlation matrices and regional motor thalamus FC differed significantly between groups. Post-hoc network-level testing revealed decreased thalamus-somatomotor, thalamus-visual, and auditory-visual FC in ET versus controls. Regional FC showed increased primary motor cortex and decreased occipital-parietal and cerebellar FC with motor thalamus in ET relative to controls. Visual-lateral somatomotor network FC negatively predicted tremor improvement with VIM DBS.

Whole-brain, network, and regional FC results demonstrate cerebello-thalamo-motor pathway dysfunction in ET. Robust FC differences in motor and visual regions related to VIM DBS outcomes. These results, employing rigorous quality control, support the need for additional investigation into the role of visual cortical networks in ET and DBS response.