Resting-State Brain Activity Changes and Their Genetic Correlates in Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) often leads to persistent cognitive and emotional symptoms, but the underlying neurobiological mechanisms remain unclear. Although previous studies have reported alterations in resting-state brain activity in mTBI patients, the findings have been inconsistent, and the genetic basis of these changes has not been fully explored. A coordinate-based voxel-wise meta-analysis was conducted to investigate resting-state brain activity changes in mTBI, using nine datasets from 374 patients and 302 healthy controls (HCs). Transcription-neuroimaging association analyses were performed using gene expression data from the Allen Human Brain Atlas (AHBA) to identify genes associated with brain activity alterations. Enrichment analyses were conducted to explore the biological functions of these genes. Compared to HCs, mTBI patients showed increased resting-state brain activity in the left insula and right fusiform gyrus, and decreased activity in the bilateral middle frontal gyrus. Transcription-neuroimaging association analyses identified 840 genes significantly correlated with these brain activity changes. Enrichment analyses revealed 15 biological processes significantly associated with the identified genes, primarily involving chemical synaptic transmission, multicellular organism development, and cell-cell signaling. These genes were also enriched in Pnoc+, Ntsr+, and Cort+ neurons and were expressed predominantly from the late fetal to early adulthood stages. Our findings suggest that alterations in resting-state brain activity in mTBI are linked to specific gene expression patterns, highlighting potential biological pathways involved in mTBI-related brain changes.