Department of Radiology, Gordon Center for Medical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Neurotechnology Laboratory, Tecnalia Health Department, Tecnalia, Derio, Spain.
Cereb Cortex. 2019 Aug 14;29(9):3828-3835. doi: 10.1093/cercor/bhy262.
Individual differences in humans are driven by unique brain structural and functional profiles, presumably mediated in part through differential cortical gene expression. However, the relationships between cortical gene expression profiles and individual differences in large-scale neural network organization remain poorly understood. In this study, we aimed to investigate whether the magnitude of sequence alterations in regional cortical genes mapped onto brain areas with high degree of functional connectivity variability across individuals. First, human genetic expression data from the Allen Brain Atlas was used to identify protein-coding genes associated with cortical areas, which delineated the regional genetic signature of specific cortical areas based on sequence alteration profiles. Thereafter, we identified brain regions that manifested high degrees of individual variability by using test-retest functional connectivity magnetic resonance imaging and graph-theory analyses in healthy subjects. We found that rates of genetic sequence alterations shared a distinct spatial topography with cortical regions exhibiting individualized (highly-variable) connectivity profiles. Interestingly, gene expression profiles of brain regions with highly individualized connectivity patterns and elevated number of sequence alterations are devoted to neuropeptide-signaling-pathways and chemical-synaptic-transmission. Our findings support that genetic sequence alterations may underlie important aspects of brain connectome individualities in humans. Significance Statement: The neurobiological underpinnings of our individuality as humans are still an unsolved question. Although the notion that genetic variation drives an individual's brain organization has been previously postulated, specific links between neural connectivity and gene expression profiles have remained elusive. In this study, we identified the magnitude of population-based sequence alterations in discrete cortical regions and compared them to the brain topological distribution of functional connectivity variability across an independent human sample. We discovered that brain regions with high degree of connectional individuality are defined by increased rates of genetic sequence alterations; these findings specifically implicated genes involved in neuropeptide-signaling pathways and chemical-synaptic transmission. These observations support that genetic sequence alterations may underlie important aspects of the emergence of the brain individuality across humans.
个体差异是由独特的大脑结构和功能特征驱动的，这可能部分是通过皮质基因表达的差异来介导的。然而，皮质基因表达谱与大规模神经网络组织的个体差异之间的关系仍知之甚少。在这项研究中，我们旨在研究个体间大脑功能连接变异性较高的脑区的区域皮质基因序列改变的幅度是否与个体间大脑网络组织的差异有关。首先，我们使用艾伦大脑图谱的人类遗传表达数据来识别与皮质区相关的蛋白编码基因，这些基因根据序列改变谱描绘了特定皮质区的区域遗传特征。此后，我们通过对健康受试者进行测试-再测试功能连接磁共振成像和图论分析，确定了表现出个体高度变异性的脑区。我们发现，遗传序列改变的比率与表现出个体连接性（高度可变）模式的皮质区具有明显的空间拓扑关系。有趣的是，具有高度个体化连接模式和较高序列改变数量的脑区的基因表达谱与神经肽信号通路和化学突触传递有关。我们的研究结果支持遗传序列改变可能是人类大脑连接组个体差异的重要基础。
