Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia

Writer's cramp (WC) dystonia is an involuntary movement disorder with distributed abnormalities in the brain's motor network. Prior studies established the potential for repetitive transcranial magnetic stimulation (rTMS) to either premotor cortex (PMC) or primary somatosensory cortex (PSC) to modify symptoms. However, clinical effects have been modest with limited understanding of the neural mechanisms hindering therapeutic advancement of this promising approach. This study aimed to understand the motor network effects of rTMS in WC that correspond with behavioral efficacy. We hypothesized that behavioral efficacy is associated with modulation of cortical and subcortical regions of the motor network. In a double-blind, cross-over design, twelve WC participants underwent rTMS in one of three conditions (Sham-TMS, 10 Hz PSC-rTMS, 10 Hz PMC-rTMS) while engaged in a writing task to activate dystonic movements and measure writing fluency. Brain connectivity was evaluated using task-based fMRI after each TMS session. 10 Hz rTMS to PSC, but not PMC, significantly improved writing dysfluency. PSC-TMS also significantly weakened cortico-basal ganglia, cortico-cerebellum, and intra-cerebellum functional connectivity (FC), and strengthened striatal FC relative to Sham. Change in PSC and SPC BOLD activity were associated with reduced dysfluent writing behavior. 10 Hz rTMS to PSC improved writing dysfluency by redistributing motor network connectivity and strengthening somatosensory-parietal connectivity. A key signature for effective stimulation at PSC and improvement in writing dysfluency may be strengthening of intra-cortical connectivity between primary somatosensory and superior parietal cortices. These findings offer mechanistic hypotheses to advance the therapeutic application of TMS for dystonia.