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

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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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Author notes

  1. Jie Zhang and Lingling Li contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Brain Medical Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, 310003, Hangzhou, China

    Jie Zhang, Renjie Ji, Xinrui Wen, Jun Hu, Li Zhang, Fangping He & Benyan Luo

  2. Center for Rehabilitation Medicine, Rehabilitation and Sports Medicine Research Institute of Zhejiang Province, Department of Rehabilitation Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, 310014, China

    Jie Zhang, Yingqiao Wang, Li Zhang & Xiangming Ye

  3. Department of Neurology, Dongyang People’s Hospital, Wenzhou Medical University, Dongyang, 322109, China

    Lingling Li

  4. Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China

    Desheng Shang

  5. Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, 310027, China

    Dan Wu

  6. MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou, 310003, China

    Benyan Luo

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  1. Jie Zhang
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Contributions

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.

Corresponding author

Correspondence to Benyan Luo.

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This study was performed in line with the principles of the Declaration of Helsinki (2013 amendment). The Ethics Committee of the First Affiliated Hospital of Zhejiang University School of Medicine approved the study.

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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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