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Dysfunction of the lenticular nucleus is thought to contribute to neurological symptoms in Wilson’s disease (WD). However, very little is known about whether and how the lenticular nucleus influences dystonia by interacting with the cerebral cortex and cerebellum.

To solve this problem, we recruited 37 WD patients (20 men; age, 23.95 ± 6.95 years; age range, 12–37 years) and 37 age- and sex-matched healthy controls (HCs) (25 men; age, 25.19 ± 1.88 years; age range, 20–30 years), and each subject underwent resting-state functional magnetic resonance imaging (RS-fMRI) scans. The muscle biomechanical parameters and Unified Wilson Disease Rating Scale (UWDRS) were used to evaluate the level of dystonia and clinical representations, respectively. The lenticular nucleus, including the putamen and globus pallidus, was divided into 12 subregions according to dorsal, ventral, anterior and posterior localization and seed-based functional connectivity (FC) was calculated for each subregion. The relationships between FC changes in the lenticular nucleus with muscle tension levels and clinical representations were further investigated by correlation analysis. Dystonia was diagnosed by comparing all WD muscle biomechanical parameters with healthy controls (HCs).

Compared with HCs, FC decreased from all subregions in the putamen except the right ventral posterior part to the middle cingulate cortex (MCC) and decreased FC of all subregions in the putamen except the left ventral anterior part to the cerebellum was observed in patients with WD. Patients with WD also showed decreased FC of the left globus pallidus primarily distributed in the MCC and cerebellum and illustrated decreased FC from the right globus pallidus to the cerebellum. FC from the putamen to the MCC was significantly correlated with psychiatric symptoms. FC from the putamen to the cerebellum was significantly correlated with muscle tension and neurological symptoms. Additionally, the FC from the globus pallidus to the cerebellum was also associated with muscle tension.

Together, these findings highlight that lenticular nucleus–cerebellum circuits may serve as neural biomarkers of dystonia and provide implications for the neural mechanisms underlying dystonia in WD.

Keywords: Wilson’s disease, lenticular nucleus, dystonia, functional connectivity, unified Wilson’s disease rating scale, muscle tension

In conclusion, our study found that aberrant FC from the lenticular nucleus to the cerebellum and MCC were observed in patients with WD. The FC changes from the lenticular nucleus to the cerebellum were related to UWDRS-N and were also significantly correlated with muscle tension levels. These findings suggested that the lenticular nucleus–cerebellum pathways may serve as neural biomarkers of dystonia and provided implications for the neural mechanisms underlying dystonia in WD. In addition, this study has potential clinical application value in that the cerebellum may serve as a potential target for TMS to treat dystonia and neurological symptoms of WD.