Brain. 2026 Sep 21:awag327. doi: 10.1093/brain/awag327. Online ahead of print.
ABSTRACT
Cervical dystonia is the most common adult-onset focal dystonia, characterized by involuntary neck muscle contractions that produce abnormal head postures, jerky or tremor-like movements, and functional impairment. The first-line treatment is botulinum toxin, which provides symptomatic relief but requires repeated injections every 3-4 months, and up to one-third of patients discontinue therapy due to suboptimal benefit or adverse effects. There is clinical evidence that physical therapy interventions, including stretching, massage techniques, and resistance training exercise reduce symptom severity and disability in cervical dystonia, yet their effects on underlying brain networks remain poorly understood. Cervical dystonia is a network disorder in which the normally seamless integration of sensory input, motor planning, and execution becomes disrupted, leading to maladaptive activation patterns of neck muscles. In a randomized controlled trial (botulinum toxin combined with physical therapy vs. botulinum toxin alone), we examined the effects of six-month, supervised, structured resistance training-based physical therapy intervention on brain networks in individuals with cervical dystonia who exhibited suboptimal response to botulinum toxin therapy (n = 42; recruited). The intervention consisted of twice-weekly, in-person sessions delivered by trained physical therapists at facilities near participants' homes, enabling sustained adherence and sufficient duration to detect clinically meaningful and brain-based adaptations. Task-based fMRI using a hand task revealed that resistance training-based physical therapy was associated with adaptive reorganization within distributed motor networks, particularly the cerebellum and cortical regions involved in motor planning and motor preparation (n = 37; complete-case analysis of participants with both pre- and post-intervention MRI scans). There was reduced blood oxygen level dependent activity observed in the cerebellum (sensorimotor and associative subregions) and pons. Functional connectivity analyses demonstrated modulation of basal ganglia-cortical, basal ganglia-cerebellar, cerebello-cortical, and thalamo-cortical networks, with increased connectivity linking the putamen and pallidum to prefrontal, sensorimotor, parietal cortices, and the cerebellum to prefrontal, cingulate, supplementary motor area, and primary motor cortex regions. Notably, changes in sensorimotor cerebellum-prefrontal cortex/precuneus connectivity were linked to clinical gains. Taken together, these findings indicate that resistance training-based physical therapy may promote motor improvement in cervical dystonia by reshaping distributed basal ganglia-cerebellar-cortical networks involved in motor planning and preparation, with the cerebellum acting as a central hub supporting efficient motor control. These results further suggest that therapeutic benefit may arise from recalibration of distributed motor circuits rather than isolated regional effects.
PMID:42766817 | DOI:10.1093/brain/awag327