Connectivity-based striatal subregion microstructural changes in sporadic amyotrophic lateral sclerosis patients: Relation to motor disability, cognitive deficits, and serum biomarkers.

Background And Purpose: To date, no previous studies have used multishell diffusion MRI to identify striatal microstructural damage in vivo in amyotrophic lateral sclerosis (ALS) patients. Thus, in the present study, we aimed to comprehensively explore connectivity-based selective striatal subregion microstructural damage in sporadic ALS patients and its associations with motor disability, cognitive deficits, and serum biomarkers.

Methods: In this retrospective study, 79 ALS patients and 53 healthy controls (HCs) who underwent clinical assessment, serum neurofilament light (NfL) measurement, genetic testing, and multishell diffusion MRI scanning were included. Using a probabilistic tractography approach, the striatum was segmented into six subregions based on their corticostriatal connectivity. Three neurite orientation dispersion and density imaging (NODDI) parameters, the neurite density index (NDI), orientation dispersion index (ODI), and isotropic volume fraction (ISO), of the connectivity-based striatal subregions were measured.

Results: Compared with HCs, ALS patients had a significantly lower NDI in the bilateral motor and right frontal subregions, a significantly lower ODI in the right motor and frontal subregions, and a significantly higher ISO in the bilateral motor and frontal subregions of the striatum after familywise error (p < 0.05). Moreover, striatal subregion microstructural damage was significantly correlated with motor disabilities, cognitive deficits, and serum NfL levels in ALS patients (p = 0.020-0.002).

Conclusions: Our study provides clear evidence demonstrating that connectivity-based selective striatal subregion microstructural damage is a definite feature of sporadic ALS patients and suggesting that striatal damage may play an important role in motor disability and cognitive deficits in ALS patients.