Cortical Morphometric Similarity Remodeling in Traumatic Brain Injury Links Cognitive Impairments with Transcriptional Changes and Type-Specific Cells

The heterogeneous injuries and resulting cognitive deficits pose significant challenges in the clinical management of mild traumatic brain injury (mTBI). However, the pathophysiological mechanisms related to heterogeneities of mTBI are still unclear. This study aims to explore the mechanisms underlying brain remodeling by examining the morphometric similarity (MS) alterations and corresponding transcriptomic signatures across adult and pediatric mTBI (adult mTBI: 112 acute patients, 47 follow-up chronic patients, 66 healthy controls [HCs]; pediatric mTBI: 30 acute patients, 31 HCs). A healthy adult cohort (N = 840) is included to derive the modularized brain MS networks representing interregional cortical connectivity. Subsequently, cortical MS remodeling patterns are identified involving mostly MS increases in the frontal modules with typical high MS and decreases in the occipital module with typical low MS, with more pronounced changes observed in the developing brain with mTBI. The abnormal MS changes are correlated with variable cognitive impairments. Moreover, cortical MS remodeling is also associated with the genes enriched in CA1 pyramidal cells and neuron-specific biological processes. The transcription-related cortical remodeling in mTBI might reveal the disruption of brain cellular architecture. Therapeutic modalities to intervene in specific cortex and tackle CA1 over-activation might better encircle the neurobiology of TBI.