Structural brain changes in the development of essential tremor: toward early diagnosis.

Background: Essential tremor (ET) is the most common movement disorder. Its etiology and neuropathology remain controversial, but could be clarified with neuroimaging. Objectives: This study investigated brain structures derived from T1-weighted MRI associated with tremor severity in analyses focusing on the motor circuit and whole-brain to test competing hypotheses. Methods: Structural MRI at 3T was acquired from 50 ET participants and 50 healthy controls (HC). Voxel-based morphometry and surface-based processing generated measures of brain structure. Three two-group comparisons were undertaken: 1) HC versus ET participants; 2) HC versus ET participants with low tremor; and 3) HC versus ET participants with high tremor. For ET participants, correlations with tremor severity were also explored. Results: Within the motor circuit and across the whole brain, no significant case-control differences were observed after correction. Likewise, vertex-wise analyses of cortical volume, cortical thickness, and gyrification did not reveal significant differences. Uncorrected voxel-wise analyses suggested subtle reductions in the cerebellum and the motor circuit, particularly in ET participants with greater tremor severity. However, these effects were generally small and not consistently observed across analyses. Conclusion: The present analysis showed that ET severity was associated with weak structural differences, mainly within the motor circuit, although these findings did not survive correction. Consistent with previous literature, structural MRI abnormalities in ET appeared subtle and heterogeneous across studies, potentially becoming more detectable in patients with more severe symptoms. Although not designed to assess disease progression directly and noting that no finding survived correction for multiple comparisons, the direction of uncorrected exploratory trends within the motor circuit is consistent with the hypothesis of progressive structural alterations; however, this interpretation remains speculative and requires replication in larger, longitudinal cohorts.