NODDI Identifies Cognitive Associations with In Vivo Microstructural Changes in Remote Cortical Regions and Thalamocortical Pathways in Thalamic Stroke

The roles of cerebral structures distal to isolated thalamic infarcts in cognitive deficits remain unclear. We aimed to identify the in vivo microstructural characteristics of remote gray matter (GM) and thalamic pathways and elucidate their roles across cognitive domains. Patients with isolated ischemic thalamic stroke and healthy controls underwent neuropsychological assessment and magnetic resonance imaging. Neurite orientation dispersion and density imaging (NODDI) was modeled to derive the intracellular volume fraction (VF) and orientation dispersion index. Fiber density (FD) was determined by constrained spherical deconvolution, and tensor-derived fractional anisotropy (FA) was calculated. Voxel-wise GM analysis and thalamic pathway tractography were performed. Twenty-six patients and 26 healthy controls were included. Patients exhibited reduced VF in remote GM regions, including ipsilesional insular and temporal subregions. The microstructural metrics VF, FD, and FA within ipsilesional thalamic pathways decreased (false discovery rate [FDR]-p < 0.05). Noteworthy associations emerged as VF within insular cortices (ρ = −0.791 to −0.630; FDR-p < 0.05) and FD in tracts connecting the thalamus and insula (ρ = 0.830 to 0.971; FDR-p < 0.001) were closely associated with executive function. The VF in Brodmann area 52 (ρ = −0.839; FDR-p = 0.005) and FA within its thalamic pathway (ρ = −0.799; FDR-p = 0.003) correlated with total auditory memory scores. In conclusion, NODDI revealed neurite loss in remote normal-appearing GM regions and ipsilesional thalamic pathways in thalamic stroke. Reduced cortical dendritic density and axonal density of thalamocortical tracts in specific subregions were associated with improved cognitive functions. Subacute microstructural alterations beyond focal thalamic infarcts might reflect beneficial remodeling indicating post-stroke plasticity.