Aberrant cortical reorganization and astrogliosis underlie memory deficit post-traumatic brain injury: a longitudinal multiscale multimodal study

Tan, J.; Patel, S.; Xu, T.; Dorr, A.; Almanza, D. L. V.; Osmann, J.; Rabelo, T.; Vecchio, L.; McLaurin, J.; Wang, C.; Lipsman, N.; Burke, M.; Aubert, I.; Hamani, C.; Stefanovic, B.; Goubran, M.

doi:10.64898/2026.10.16.759571

bioRxiv · 10.64898/2026.10.16.759571

Aberrant cortical reorganization and astrogliosis underlie memory deficit post-traumatic brain injury: a longitudinal multiscale multimodal study

Tan, J.·Patel, S.·Xu, T.·Dorr, A.·Almanza, D. L. V.·Osmann, J.·Rabelo, T.·Vecchio, L.·McLaurin, J.·Wang, C.·Lipsman, N.·Burke, M.·Aubert, I.·Hamani, C.·Stefanovic, B.·Goubran, M.

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Abstract

Integrating high-dimensional neuroimaging data across spatial scales remains a fundamental bottleneck in quantitative neuroscience. Here, we apply emerging analytical techniques including functional connectome gradient mapping and 3D segmentation of whole-brain cellular resolution microscopy data in a mouse model of traumatic brain injury. At the macroscale, longitudinal functional MRI revealed a transition from frontal hyperconnectivity to hippocampal hypoconnectivity and unimodal-transmodal gradient contraction indicating network dedifferentiation. At the cellular scale, deep-learning based segmentation of whole-brain light-sheet fluorescence microscopy volumes quantified regional astrogliosis, neuronal hyperactivity, and single-axon loss undetected by standard diffusion MRI. Multiscale multimodal data integration not only identified quantitative biomarkers predictive of memory performance post-injury but also enabled validation of in vivo modalities against more sensitive ex vivo histology. This study demonstrates a framework for probing complex multi-network cognitive functions and neurological disorders of network dysfunction.

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Tan, J., Patel, S., Xu, T., Dorr, A., Almanza, D. L. V., Osmann, J., Rabelo, T., Vecchio, L., McLaurin, J., Wang, C., Lipsman, N., Burke, M., Aubert, I., Hamani, C., Stefanovic, B., Goubran, M.. 2026-10-22. Aberrant cortical reorganization and astrogliosis underlie memory deficit post-traumatic brain injury: a longitudinal multiscale multimodal study. https://doi.org/10.64898/2026.10.16.759571

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