Abstract
The central pathology causing idiopathic focal dystonia remains unclear, limiting effective treatment targets. The recently identified somato-cognitive action network (SCAN) with its role in coordinating physiologic processes and coarse movements has been implicated in dystonia dysfunction. SCAN is thought to interface between the phylogenetically newer primary motor regions that control fine movements and the cingulo-opercular network (CON) that putatively conveys cognitive intentions for action. We hypothesized that the effector-agnostic nature of SCAN may constitute a central pathology shared across focal dystonia subtypes affecting different body parts. Additionally, the effector-specific areas in the primary sensorimotor cortex may show distinct functional changes depending on the dystonic body region. We collected functional MRI from patients with either of two subtypes of focal dystonia (laryngeal dystonia or LD, N =24, and focal hand dystonia or FHD, N =18) and healthy control participants ( N =21). Regions of interest were selected based on prior work that suggested dystonia-related abnormality within the basal-ganglia-thalamo-cortical and cerebello-thalamo-cortical sensorimotor circuitries. We investigated if focal dystonia is associated with resting-state functional connectivity changes 1) between SCAN and other cortical regions (effector-specific areas and CON), 2) between cortical and non-cortical regions, or 3) between non-cortical (subcortical and cerebellar) regions. Cortical regions were individualized based on resting-state data. Separately, individualized hand and mouth/larynx regions were also generated from task-based MRI (finger-tapping and phonation, respectively) for comparison. There was a shared interaction effect in both focal dystonia subtypes ( p =0.048 for LD, p =0.017 for FHD) compared to controls, which was driven by SCAN′s higher functional connectivity to task-derived mouth/larynx region and concomitantly lower connectivity to CON. This dystonia-dependent interaction was not observed with the resting-state mouth/larynx region. No significant resting-state functional changes were observed involving subcortical and cerebellar regions when LD and FHD were modeled as independent groups. However, exploratory analysis combining LD and FHD suggested a dystonia-dependent asynchronization between SCAN and sensorimotor cerebellum ( p =0.010) that may indicate a pathological rather than compensatory process. For the first time, our study systematically tested circuitry-based functional connectivity changes in two focal dystonias. Our results show that SCAN is uniquely associated with dystonia dysfunction beyond the dystonic effector regions, potentially offering insights on pathophysiology and treatments.
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