# Subcortical microstructural impairment in amyotrophic lateral sclerosis: clinical correlates of neurite orientation dispersion and density imaging (NODDI) changes

## TL;DR

This study explores subcortical brain changes in ALS using NODDI imaging, finding some uncorrected links between microstructural metrics and clinical disability.

## Contribution

The study introduces NODDI as a potential tool to detect subcortical microstructural changes in ALS.

## Key findings

- Higher ODI in the left thalamus was linked to reduced respiratory function in ALS patients.
- Amygdala ODI showed nominal associations with fine-motor subscores in ALS.
- Thalamic and caudate NDI correlated with gross motor function in ALS patients.

## Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving widespread network disruption beyond the motor cortex. Deep gray matter (DGM) nuclei, crucial for motor and cognitive integration, remain underexplored in vivo. This study applied neurite orientation dispersion and density imaging (NODDI) to evaluate DGM microstructure and its relationship with clinical disability in ALS.

Diffusion-weighted MRI data were acquired from 23 ALS patients and 24 age- and sex-matched healthy controls. Orientation dispersion index (ODI), neurite density index (NDI), and free water fraction (FWF) were extracted from the bilateral thalamus, caudate, putamen, pallidum, hippocampus, and amygdala using the Destrieux atlas. Group comparisons and partial correlations were adjusted for age, sex, and disease duration.

No significant group differences in DGM volumes or NODDI-derived metrics survived correction for multiple comparisons. Within the ALS group, several nominal (uncorrected) associations were observed between DGM microstructural metrics and ALSFRS-R subscores. Reduced respiratory subscores were associated with higher ODI in the left thalamus (ρ = 0.57, p = 0.0047, uncorrected). Fine-motor subscores showed nominal positive associations with ODI in the left (ρ = 0.48, p = 0.021, uncorrected) and right amygdala (ρ = 0.51, p = 0.012, uncorrected). Gross motor subscores were nominally associated with NDI in the right thalamus (ρ = 0.58, p = 0.004, uncorrected), left thalamus (ρ = 0.42, p = 0.047, uncorrected), left caudate (ρ = 0.52, p = 0.011, uncorrected), and right caudate (ρ = 0.57, p = 0.033, uncorrected). None of these associations survived false discovery rate correction and should therefore be interpreted as exploratory.

These findings suggest subtle and predominantly exploratory associations between DGM microstructural properties and clinical measures in ALS. NODDI derived metrics, particularly ODI and NDI, may provide sensitive indices of subcortical microstructural variation, warranting further investigation in larger cohorts.