TMS target comparison identifies motor network reorganization associated with behavioral improvement in writer’s cramp dystonia: A randomized, double-blind, Sham-controlled clinical trial

Background

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.

Objective

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.

Methods

In a double-blind, cross-over design, twelve WC participants underwent weekly 10 Hz rTMS in one of three conditions (Sham-TMS, PSC-TMS, PMC-TMS) 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.

Results

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 connectivity relative to Sham. Increased PSC BOLD activity was associated with reduced dysfluent writing behavior.

Conclusions

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.

Highlights

• 10 Hz repetitive TMS to somatosensory cortex reduces writing dysfluency in dystonia

• Increased somatosensory cortex activity correlates with reduced writing dysfluency

• In untreated dystonia, writing dysfluency correlates with cerebellar connectivity.

• 10 Hz rTMS to somatosensory cortex induces reorganization of the motor network

• Somatosensory-parietal connectivity may be a key signature for effective TMS