Cerebellar connectome alterations and associated genetic signatures in multiple sclerosis and neuromyelitis optica spectrum disorder

Yuping Yang, Junle Li, Ting Li, Zhen Li, Zhizheng Zhuo, Xuemei Han, Yunyun Duan, Guanmei Cao, Fenglian Zheng, Decai Tian, Xinli Wang, Xinghu Zhang, Kuncheng Li, Fuqing Zhou, Muhua Huang, Yuxin Li, Haiqing Li, Yongmei Li, Chun Zeng, Ningnannan ZhangJie Sun, Chunshui Yu, Fudong Shi, Umer Asgher, Nils Muhlert, Yaou Liu, Jinhui Wang

Research output: Contribution to journalArticlepeer-review


BACKGROUND: The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown.

METHODS: Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles.

RESULTS: Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases.

CONCLUSIONS: We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.

Original languageEnglish
Pages (from-to)352
JournalJournal of Translational Medicine
Issue number1
Publication statusPublished - 27 May 2023


  • Humans
  • Multiple Sclerosis/diagnostic imaging
  • Neuromyelitis Optica/diagnostic imaging
  • Connectome
  • Brain/diagnostic imaging
  • Magnetic Resonance Imaging
  • Cerebellum/diagnostic imaging


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