Diffusion and functional MRI reveal microstructural and network connectivity impairment in adult-onset neuronal intranuclear inclusion disease.

Objectives: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder lacking reliable neuroimaging biomarkers. This study aimed to evaluate microstructural and functional connectivity alterations using diffusion kurtosis imaging (DKI) and resting-state fMRI (rs-fMRI), and to investigate their diagnostic potential as biomarkers.

Methods: Twenty-three patients with NIID and 40 matched healthy controls (HCs) were recruited. Firstly, gray matter (GM) and white matter (WM) changes were assessed by voxel-based analysis (VBA) and tract-based spatial statistics (TBSS). Then we explored modifications in brain functional networks connectivity by independent component analysis. And the relationship between the altered DKI parameters and neuropsychological evaluation was analyzed. Finally, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of different gray matter and white matter parameters.

Results: Compared with the HCs, NIID patients showed reduced mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), and kurtosis fractional anisotropy (KFA) values in deep gray matter regions. Significantly decreased MK, RK, AK, KFA and fractional anisotropy (FA), and increased mean diffusivity (MD) values were observed in extensive white matter fiber tracts. Notable alterations in functional connectivity were also detected. Among all DKI parameters, the diagnostic efficiency of AK in GM and FA in WM regions was the highest.

Conclusion: Adult-onset NIID patients exhibited altered microstructure and functional network connectivity. Our findings suggest that DKI parameters may serve as potential imaging biomarkers for diagnosing adult-onset NIID.