Structural abnormalities in thalamo-prefrontal tracks revealed by high angular resolution diffusion imaging predict working memory scores in concussed children
Because of their high prevalence, heterogeneous clinical presentation, and wide-ranging sequelae, concussions are a challenging neurological condition, especially in children. Shearing forces transmitted across the brain during concussions often result in white matter damage. The neuropathological impact of concussions has been discerned from animal studies and includes inflammation, demyelination, and axonal loss. These pathologies can overlap during the sub-acute stage of recovery. However, due to the challenges of accurately modeling complex white matter structure, these neuropathologies have not yet been differentiated in children in vivo. In the present study, we leveraged recent advances in diffusion imaging modeling, tractography, and tractometry to better understand the neuropathology underlying working memory problems in concussion. Studying a sample of 16 concussed and 46 healthy youths, we used novel tractography methods to isolate 11 working memory tracks. Along these tracks, we measured fractional anisotropy, diffusivities, track volume, apparent fiber density, and free water fraction. In three tracks connecting the right thalamus to the right dorsolateral prefrontal cortex (DLPFC), we found microstructural differences suggestive of myelin alterations. In another track connecting the left anterior-cingulate cortex with the left DLPFC, we found microstructural changes suggestive of axonal loss. Structural differences and tractography reconstructions were reproduced using test–retest analyses. White matter structure in the three thalamo-prefrontal tracks, but not the cingulo-prefrontal track, appeared to play a key role in working memory function. The present results improve understanding of working memory neuropathology in concussions, which constitutes an important step toward developing neuropathologically informed biomarkers of concussion in children.
KeywordsConcussion Mild TBI Diffusion-weighted imaging Constrained spherical deconvolution
We want to thank the participants and their parents for lending their time for this study. We also want to thank Dr. Jen-Kai Chen and Dr. Rajeet Singh Salujah for their contribution in the acquisition of this data.
Funding for this study came from: 1. a Vanier Canada Graduate Research award, the Fonds de Recherche du Quebec—Doctoral Training for Medical Students award, and the Tomlinson Doctoral Fellowship award (G. I. Guberman); 2. an Institutional Research Chair in Neuroinformatics and National Science and Engineering Research Council Discovery Grants (Dr. Descoteaux); 3. a Canadian Institutes of Health Research Grant (Dr. Ptito, Dr. Gagnon); 4. A Fonds de Recherche du Quebec senior clinical research scholar award, and support from the Research Institute of the McGill University Health Centre (Dr. Gagnon).
Compliance with ethical standards
Conflict of interest
The authors have no conflicts of interest to declare.
Every participant provided informed written consent as approved by the ethics committee at McGill University, Montreal Neurological Institute.
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