Function-Specific Localization in the Supplementary Motor Area: A Potential Effective Target for Tourette Syndrome.

Aims: Repetitive transcranial magnetic stimulation (rTMS) targeting the supplementary motor area (SMA) may treat Tourette's syndrome (TS) by modulating the function of the globus pallidus internus (GPi) via the cortico-striato-thalamo-cortical circuit.

Methods: We conducted a randomized longitudinal study to examine circuit functionality and clinical efficacy. The GPi was identified as an "effective region" for TS treatment. Using functional MRI, individualized targets within the SMA were identified. Function-specific targets [left SMA (n = 19), right SMA (n = 16)] were compared with conventional scalp-localized SMA targets (n = 19). Age- and gender-matched typical developmental children (TDC) served as controls (n = 48). TS patients received 50 Hz continuous theta burst stimulation (cTBS) at 70% RMT over five consecutive days (1800 pulses/day). Clinical efficacy was assessed using the Yale Global Tic Severity Scale (YGTSS) at one and two weeks post-cTBS. Functional connectivity (FC) analyses of the GPi evaluated the impact on brain function.

Results: There was an approximately 3 cm Y-axis distance between the function-specific and conventional targets. TS patients exhibited significantly reduced GPi-base FC in bilateral motor areas at baseline compared to TDC. Following cTBS, 4 out of 19 patients in the left SMA group achieved a ≥ 30% reduction in YGTSS scores. cTBS modulated brain function in the left inferior orbital frontal cortex and right Lingual/cerebellum, primarily influenced by the right SMA target, whereas the conventional target showed no effect on YGTSS scores. Changes in GPi-target FC were significantly correlated with reduction in YGTSS total scores (r = 0.638, p = 0.026).

Conclusion: These findings suggest that function-specific SMA targets may yield more pronounced modulatory effects, with the left SMA target achieving "Effectiveness" after just one week of cTBS. Combining function-specific SMA-targeted cTBS with standard treatment shows promise in accelerating clinical efficacy for TS treatment, warranting further investigation.