Wang Lu, Zhang Yijing, Wang He, Wang Xinyu, Wang Wei, Qiao Jin, Zhang Zhihui, Lei Minghuan, Cai Wenjie, An Qi, Song Linlin, Liu Feng, Ma Juanwei
Department of Geriatrics and Tianjin Geriatrics Institute, Tianjin Medical University General Hospital, Tianjin, China.
Department of Radiology and Tianjin key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China.
Hum Brain Mapp. 2025 Jun 1;46(8):e70259. doi: 10.1002/hbm.70259.
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.
轻度创伤性脑损伤（mTBI）常导致持续的认知和情绪症状，但其潜在的神经生物学机制仍不清楚。尽管先前的研究报道了mTBI患者静息态脑活动的改变，但结果并不一致，且这些变化的遗传基础尚未得到充分探索。我们进行了一项基于坐标的体素元分析，以研究mTBI患者静息态脑活动的变化，使用了来自374例患者和302名健康对照（HCs）的9个数据集。利用艾伦人类脑图谱（AHBA）的基因表达数据进行转录-神经影像关联分析，以识别与脑活动改变相关的基因。进行富集分析以探索这些基因的生物学功能。与HCs相比，mTBI患者左侧岛叶和右侧梭状回的静息态脑活动增加，双侧额中回的活动减少。转录-神经影像关联分析确定了840个与这些脑活动变化显著相关的基因。富集分析揭示了15个与所识别基因显著相关的生物学过程，主要涉及化学突触传递、多细胞生物体发育和细胞间信号传导。这些基因在Pnoc+、Ntsr+和Cort+神经元中也有富集，并且主要在胎儿晚期到成年早期表达。我们的研究结果表明，mTBI患者静息态脑活动的改变与特定的基因表达模式有关，突出了mTBI相关脑变化所涉及的潜在生物学途径。
