Focal Dystonia: Functional Connectivity Changes in Cerebellar-Basal Ganglia-Cortical Circuit and Preserved Global Functional Architecture

Background and objectives: Neuroimaging studies suggest that changes in the cerebellar-basal ganglia-thalamo-cortical sensorimotor circuit are a pathophysiological feature of focal dystonia. However, it remains unclear whether structural and functional alterations vary in different forms of focal dystonia. Thus, in patients with cervical dystonia (CD) and blepharospasm (BSP), we aimed to investigate structural damage and resting-state functional alterations using whole-brain and seed-based approaches to test the hypothesis of possible functional connectivity (FC) alterations in specific circuits, including the cerebellum, basal ganglia, and cerebral cortex, in the context of preserved global FC. Methods: In this cross-sectional study we applied a multimodal 3T MRI protocol, including 3D T1-weighted images to extract brain volumes and cortical thickness, and functional MRI at rest to study functional connectivity (FC) of the dentate nucleus and globus pallidus with a seed-based approach, and whole-brain FC with a graph theory approach. Results: This study included 33 patients [17 with CD (14 females) aged 55.7±10.1 years and 16 with BSP (11 females) aged 62.9±8.8 years], and 16 age- and sex-matched healthy subjects (HS) (7 females) aged 54.3±14.3 years. CD patients, BSP patients, and HS did not differ in terms of cortical or subcortical volume. Compared to HS, both CD and BSP patients had a loss of dentate FC anticorrelation with the sensorimotor cortex. CD and BSP patients showed increased pallidal FC with the cerebellum, supplementary motor area, and prefrontal cortices with respect to HS. Increased dentate FC with the cerebellum and thalamus and increased pallidal FC with the bilateral thalamus, sensorimotor and temporo-occipital cortices, and right putamen were present in CD but not BSP patients, as compared to HS. Measures of global FC, i.e., global efficiency and small-worldness, did not differ between patients and HS. Conclusion: Both CD and BSP patients showed altered dentate and pallidal FC with regions belonging to the integrated cerebellar-basal ganglia-thalamo-cortical sensorimotor circuit, supporting the concept that focal dystonia is a disorder of specific networks, and not merely a result of basal ganglia alterations, in the context of a preserved whole-brain functional architecture. Differences in functional interplay among specific brain structures may distinguish CD and BSP.