Hand‐Specific Engagement of Cerebello–Thalamo–Cortical and Higher‐Order Sensorimotor Networks in Essential Tremor: Converging Evidence From GLM and MVPA ‐Based fMRI Analysis

BACKGROUND: Essential tremor (ET) is a prevalent movement disorder affecting the upper limbs, yet the neural basis of hand-specific motor dysfunction remains incompletely understood. Most fMRI studies have not explicitly addressed lateralization of tremor-related brain activity. This study used both multivariate pattern analysis (MVPA) and univariate general linear modeling (GLM) to characterize brain network engagement during right- and left-hand movements in ET. METHODS: Eighteen right-handed ET patients and 18 age-matched healthy volunteers performed alternating right- and left-hand finger-tapping tasks during fMRI. Whole-brain GLM assessed subject-level BOLD activation, and searchlight MVPA quantified subject-level local decoding performance. Group-level analyses compared activation and decoding patterns between groups, and associations with hand-specific tremor severity were examined within the ET group. RESULTS: During right-hand finger-tapping, ET patients exhibited bilateral motor network engagement. GLM revealed reduced BOLD activity in the thalami and right supramarginal gyrus, while MVPA showed decreased decoding in the right supramarginal gyrus. In left-hand finger-tapping, a more lateralized pattern emerged, with diminished activation and decoding performance in the right thalamus and right supramarginal gyrus. Left cerebellar involvement differed between tasks and showed putative compensatory engagement, and right insular activity was associated with tremor severity during task performance. Overall, cortical alterations were predominantly right lateralized across both hands. CONCLUSIONS: ET is associated with hand-specific differences in task-related network engagement, involving cerebello-thalamo-cortical and higher-order sensorimotor regions. Right-hand movements engaged more bilateral motor circuits, whereas left-hand movements showed relatively stronger right-hemispheric involvement, suggesting lateralized task-related network alterations in ET.