Transcriptional expression patterns of orientation dispersion index of white matter in neuromyelitis optica spectrum disorder.

AIM: Neuromyelitis optica spectrum disorder (NMOSD) is characterised by complex white matter (WM) structural abnormalities, yet the underlying genetic mechanisms remain largely unexplored. This study investigated the intricate relationships between cognitive impairment, genetic factors, and brain WM structure in NMOSD.

MATERIALS AND METHOD: We performed diffusion magnetic resonance imaging (MRI) on 43 NMOSD patients and 39 age-, sex-, and education-matched healthy controls. Utilising whole-brain voxel-wise tract-based spatial statistics and neurite orientation dispersion and density imaging (NODDI), we conducted detailed analyses of WM microstructural changes. Clinical parameter correlations were assessed, and transcriptome-neuroimaging analyses were performed using the Allen Human Brain Atlas to explore gene expression patterns associated with NODDI parameter variations.

RESULTS

NMOSD participants exhibited significantly elevated orientation dispersion index (ODI) in critical WM regions, including the corpus callosum, left corona radiata, left superior longitudinal fasciculus, and right superior corona radiata. Mean ODI values demonstrated significant correlations with neurocognitive assessments, including Digit Symbol Substitution Test and Trail-Making Test. Functional enrichment analysis revealed complex gene associations involving protein metabolism, inflammatory responses, immune regulation, and synaptic signalling mechanisms.

CONCLUSION

Our study demonstrated alterations in the WM ODI in NMOSD, and uncovered their correlations with neurocognitive impairment as well as genetic profiles. This provides insights into transcriptional expression patterns and potential biomarkers for NMOSD pathogenesis.