Objective: To investigate structural and microstructural brain changes following transcranial magnetic stimulation (TMS) in essential tremor (ET) using exploratory MRI measures within a randomized controlled trial.

Background: ET is associated with dysfunction in the cerebello-thalamo-cortical (CTC)network. Although TMS has been explored as a noninvasive treatment, evidence of treatment-related brain changes remains limited. This trial compared dual-target stimulation of the left primary motor cortex(M1) and right cerebellum with single-target cerebellar stimulation in a randomized design.

Method: Twenty-four patients with ET were randomized to receive dual-target, single-target, or sham stimulation. Dual-target stimulation combined continuous theta burst stimulation of the left M1 with 1 Hz stimulation of the right cerebellum, whereas single-target stimulation involved only the right cerebellum. MRI scans were acquired at baseline, day 10, and week 4. Exploratory imaging outcomes included cortical morphometry, subcortical volumetry, and diffusion metrics derived from free-water imaging.

Results: A significant group-by-time interaction was observed in the left paracentral lobule. Post hoc analysis revealed increased cortical thickness in the single-target group at day 10 compared to baseline (β = 0.056, 95% CI 0.008 to 0.104), but not at week 4 (Figure 1). No significant interactions were detected in other pre-specified cortical thickness regions of interest (ROIs) or subcortical volumetric measures. Among diffusion metrics, putaminal free-water-corrected mean diffusivity exhibited a significant group-by-time interaction (P = 0.002, FDR-corrected P = 0.013), primarily driven by a reduction from baseline at week 4 in the single-target group (β = -0.0101, 95% CI -0.0170 to -0.0032, FDR-corrected P = 0.018) (Figure 2). The between-group difference compared to sham at week 4 did not survive FDR correction. No other diffusion measures showed significant interactions after correction. Overall, MRI changes were localized and short-term.

Conclusion: TMS induced localized and short-term MRI changes in ET, particularly in the left paracentral lobule and putaminal free-water-corrected mean diffusivity, suggesting a limited but measurable modulation of motor-related brain networks.

Figure 1

Figure 2

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MDS Abstracts - https://www.mdsabstracts.org/abstract/local-brain-structural-changes-after-transcranial-magnetic-stimulation-for-essential-tremor-an-exploratory-mri-analysis/