RT Journal Article
T1 Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain
A1 Xin, Qilong
A1 Ortiz-Terán, Laura
A1 Diez, Ibai
A1 Perez, David L.
A1 Ginsburg, Julia
A1 El Fakhri, Georges
A1 Sepulcre, Jorge
AB 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.
SN 1047-3211
YR 2019
FD 2019-09-01
LK https://hdl.handle.net/11556/3074
UL https://hdl.handle.net/11556/3074
LA eng
NO Xin , Q , Ortiz-Terán , L , Diez , I , Perez , D L , Ginsburg , J , El Fakhri , G & Sepulcre , J 2019 , ' Sequence Alterations of Cortical Genes Linked to Individual Connectivity of the Human Brain ' , Cerebral Cortex , vol. 29 , no. 9 , pp. 3828-3835 . https://doi.org/10.1093/cercor/bhy262
NO Publisher Copyright: © 2018 The Author(s).
NO This work has been partially supported by the National Institutes of Health [grant K23EB019023 (J.S.) and grant 2T32EB013180-06 (L.O.T.) from the National Institute of Biomedical Imaging and Bioengineering (N.I.B.I.B.); and grant K23MH111983 (D.P.) from National Institute of Mental Health (N.I.M.H.)], the Basque Country Government [Post-Doctoral Fellowship Program (I.D.)] and the Sidney Baer jr. Foundation (D.P.).
DS TECNALIA Publications
RD 26 jul 2024