Aberrant Cortical Reorganization and Astrogliosis Underlie Memory Deficit Post-Traumatic Brain Injury: A Longitudinal Multiscale Multimodal

Authors:
  • JTJazlynn Xiu Min Tan
    Jazlynn Xiu Min Tan
  • TXTony Xu
    Tony Xu
  • SPShruti Patel
    Shruti Patel
  • ADAdrienne Dorr
    Adrienne Dorr
  • JOJonas Osmann
    Jonas Osmann
  • TRThallita Rabelo
    Thallita Rabelo
  • LVLaura Vecchio
    Laura Vecchio
  • JMJoAnne McLaurin
    JoAnne McLaurin
  • CWChao Wang
    Chao Wang
  • NLNir Lipsman
    Nir Lipsman
  • MBMatthew Burke
    Matthew Burke
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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.