Continuous theta-burst stimulation to a lesion network in cervical dystonia: a randomized, double-blind, sham-controlled, pilot trial

Background: The mechanisms driving cervical dystonia remain unclear, limiting effective, non-invasive treatment development. Lesion network mapping previously localized a brain network derived from lesions causing cervical dystonia, with a network hub in the somatosensory cortex, a viable target for non-invasive brain stimulation. Objectives: We conducted a randomized, sham-controlled, crossover trial administering continuous theta-burst stimulation (cTBS) to the S1 lesion network hub, testing whether modulating this network reduces CD symptoms. Methods: Thirteen idiopathic cervical dystonia patients (57.85 {+/-} 10.85 years) received two 10-session blocks of bilateral somatosensory cortex cTBS (active or sham; counterbalanced). The primary outcome was change in cervical dystonia symptoms, measured by the Toronto Western Spasmodic Torticollis Scale (TWSTRS). A wearable motion sensor objectively measured change in head and neck movement patterns. Motor evoked potentials and resting-state fMRI assessed cTBS-induced changes in corticospinal excitability and functional connectivity, respectively. Results: Active cTBS did not significantly reduce cervical dystonia symptoms compared to sham (condition x timepoint interaction: p = .149). Range of motion significantly increased with active, versus sham, cTBS (p = .015). Corticospinal excitability decreased following sham (p = .042), but not active, cTBS. No significant connectivity changes were seen from the somatosensory cortex stimulation site after active cTBS; however, significant changes emerged from the globus pallidus interna. Conclusion: This study prospectively tested the effects of neuromodulation on a lesion network mapping-derived target. Active cTBS did not significantly improve TWSTRS scores relative to sham. The intervention was well tolerated by all patients, and future studies could consider higher-dose or alternative protocols to this target.