Regional, not global, functional connectivity contributes to isolated focal dystonia.

Objective: To test the hypothesis that there is shared regional or global functional connectivity dysfunction in a large cohort with isolated focal dystonia affecting different body regions compared to control participants. In this case-control study we obtained resting-state MRI scans (3-4 7.3 minute runs) with eyes closed in participants with focal dystonia (cranial [17], cervical [13], laryngeal [18], limb [10]) and age- and sex-matched controls. Methods: Rigorous preprocessing for all analyses was performed to minimize effect of head motion during scan acquisition (dystonia N=58, control N=47 analyzed). We assessed regional functional connectivity by computing a seed-correlation map between putamen, pallidum, and sensorimotor cortex and all brain voxels. We assessed significant group differences on a cluster-wise basis. In a separate analysis, we applied 300 seed regions across the cortex, cerebellum, basal ganglia and thalamus to comprehensively sample the whole brain. We obtained participant whole-brain correlation matrices by computing the correlation between seed average time courses for each seed pair. Weighted object-oriented data analysis assessed group-level whole-brain differences. Results: Participants with focal dystonia had decreased functional connectivity at the regional level, within the striatum and between lateral primary sensorimotor cortex and ventral intraparietal area, whereas whole-brain correlation matrices did not differ between focal dystonia and control groups. Rigorous quality control measures eliminated spurious large-scale functional connectivity differences between groups. Conclusion: Regional functional connectivity differences, not global network level dysfunction, contributes to common pathophysiological mechanisms in isolated focal dystonia. Rigorous quality control eliminated spurious large-scale network differences between focal dystonia and control participants.