Abstract
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 (VFic) 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 VFic in remote GM regions, including ipsilesional insular and temporal subregions. The microstructural metrics VFic, FD, and FA within ipsilesional thalamic pathways decreased (false discovery rate [FDR]-p < 0.05). Noteworthy associations emerged as VFic 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 VFic 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.
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Data Availability
Data are available upon reasonable request. Anonymized data used in this study are available to qualified investigators on reasonable request to the corresponding author.
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Acknowledgements
The authors are grateful to the patients, their families, and the healthy volunteers for their participation.
Funding
This work was funded by grants from the National Natural Science Foundation of China (82272592) (J.Z.), Key Research and Development Program of Zhejiang Province (2022C03064) (B.L.), Natural Science Foundation of Zhejiang Province (LGF22H170003) (J.Z.), and Medical and Health Science and Technology Project of Zhejiang Province (2022KY067) (J.Z.). It also received support from MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University.
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B.L. and J.Z. were responsible for contributing to the study’s concept and design. L.L., D.S., R.J., Y.W., and L.Z. were involved in data acquisition, while J.Z., X.W., J.H., F.H., and D.W. conducted the statistical analysis and interpretation. The manuscript was drafted by J.Z. and L.L. All authors participated in the manuscript revision for intellectual content. Study supervision was provided by B.L. and X.Y.
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Zhang, J., Li, L., Ji, R. et al. NODDI Identifies Cognitive Associations with In Vivo Microstructural Changes in Remote Cortical Regions and Thalamocortical Pathways in Thalamic Stroke. Transl. Stroke Res. (2023). https://doi.org/10.1007/s12975-023-01221-w
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DOI: https://doi.org/10.1007/s12975-023-01221-w