Distinct Roles of Cerebellar Afferent and Efferent Fiber Tracts in Craniocervical Dystonia

Abstract Background The cerebellum has been widely implicated in the pathogenesis of craniocervical dystonia (CCD). Subthalamic nucleus deep brain stimulation (STN‐DBS) has emerged as an effective therapy for CCD. However, the roles of cerebellar afferent and efferent pathways in CCD pathogenesis and STN‐DBS treatment remain poorly understood. Objectives To identify microstructural and connectivity alterations in the cerebellar afferent/efferent pathways in CCD, and to investigate their associations with clinical characteristics. Methods We enrolled 31 CCD patients undergoing STN‐DBS and 33 age‐ and sex‐matched healthy controls. Probabilistic tractography was performed to reconstruct three paired tracts: decussating dentato‐rubro‐thalamic tract (d‐DRTT), non‐decussating dentato‐rubro‐thalamic tract (nd‐DRTT), and subthalamo‐ponto‐cerebellar tract (SPCT). First, we quantified and compared whole‐tract mean fractional anisotropy (FA), along‐tract FA, and structural connectivity strength between groups. Second, we assessed correlations between these structural metrics and clinical variables (disease duration, baseline severity, and DBS improvement). Finally, volume of tissue activated (VTA)‐seeded tractography was conducted to explore its relationship with DBS outcomes in the CCD group. Results Compared with healthy controls, CCD patients presented significantly higher FA in bilateral nd‐DRTT, particularly in regions corresponding to the red nucleus and superior cerebellar peduncle. Moreover, bilateral VTA‐cerebellum connectivity showed a significant positive association with DBS outcomes. Conclusions Our study revealed a functional segregation of cerebellar pathways in CCD: the efferent pathways were linked to disease pathogenesis, whereas the afferent pathways were associated with STN‐DBS outcomes. This study will foster a better understanding of the pathophysiological mechanisms of CCD and facilitate the development of optimized DBS strategies. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.