Multimodal MRI reveals structural and functional alterations in isolated cervical dystonia: associations with motor severity and affective symptoms.

Introduction: Isolated cervical dystonia (ICD) is the most common focal dystonia, characterized by involuntary neck muscle contractions leading to abnormal head postures and nonmotor symptoms such as anxiety. Although structural and functional brain alterations have been reported, findings remain inconsistent, and the neurobiological mechanisms underlying motor and nonmotor symptoms remain incompletely understood. Methods: Thirty-five ICD patients and twenty-eight matched healthy controls underwent structural MRI and resting-state fMRI. Voxel-based morphometry was used to assess gray matter volume (GMV) differences. Seed-based resting-state functional connectivity (rsFC) analyses were performed using regions with significant structural alterations. Partial correlation and mediation analyses examined associations among brain measures, motor severity, and mood symptoms. Results: ICD patients showed reduced GMV in the left paracentral lobule (PCL) and right middle temporal gyrus (MTG). The left PCL exhibited altered connectivity with prefrontal, temporal, and thalamic regions, indicating disruption of cerebello-thalamo-cortical pathways. The right MTG showed decreased connectivity with the left temporal pole and increased connectivity with the right middle frontal gyrus, suggesting compensatory mechanisms for cognitive processing. GMV reduction in the left PCL significantly mediated the relationship between ICD status and anxiety symptoms. Discussion: These findings support ICD as a network disorder involving both motor and cognitive-affective circuits. Structural alterations in the PCL and MTG and their connectivity patterns may underlie motor dysfunction and nonmotor symptoms such as anxiety. Multimodal neuroimaging biomarkers may help guide targeted therapeutic interventions and improve clinical outcomes in ICD.