Structural and functional network changes following thalamotomy for focal dystonia: a multimodal MRI study

Converging evidence supports dystonia as a disorder of large-scale brain networks arising from dysfunction within, or impaired communication between, nodes of the cortico-basal ganglia-thalamo-cortical and cerebello-thalamo-cortical circuits. Focal hand dystonia is associated with abnormalities across cortical and subcortical networks. High intensity focused ultrasound (HiFU) offers a novel therapeutic approach that provides an opportunity to examine treatment related structural and functional network changes. Eleven individuals with focal hand dystonia, of musician's dystonia and writer's cramp subtype, underwent multimodal MRI, including structural analysis, diffusion tensor imaging (DTI), and resting-state functional MRI (rs-fMRI) at baseline, with comparison made to ten age- and sex-matched healthy control participants. These imaging metrics were repeated at 1, 3 and 12 months following HiFU ventro-oral (Vo)-complex thalamotomy. This trial was registered with the Australia New Zealand Clinical Trials Registry (ACTRN12622000775718p). No differences in regional volumes were observed at baseline between the groups. Following thalamotomy, small uncorrected volumetric changes were noted in several regions of interest, and DTI demonstrated lower tract-wise fractional anisotropy (FA) and coefficient of linearity (CL) within the treated pallidothalamic tract, with node-wise analysis demonstrating focal microstructural alterations that were most apparent at 12 months following treatment. There were no corresponding changes in fronto-striatal or fronto-thalamic tracts. rs-fMRI revealed baseline alterations in intra- and inter-network connectivity involving sensorimotor, visual, attentional, default mode and executive networks. Following thalamotomy, changes in functional connectivity were modest and temporally variable, without evidence of large-scale network reorganisation. These findings suggest that focal hand dystonia is associated with distributed functional network dysfunction, in the context of preserved macroscopic structure. We propose that Vo-complex thalamotomy is associated with focal, localized microstructural alterations within the pallidothalamic tract, most notable at 12 months, which may contribute to modulation of pathological pallidothalamic drive rather than widespread restoration of functional network connectivity.