Regulation of gene expression drives protein interactions that govern synaptic wiring and neuronal activity. The resulting coordinated activity among neuronal populations supports complex psychological processes, yet how gene expression shapes cognition and emotion remains unknown. Here, we directly bridge the microscale and macroscale by mapping gene expression patterns to functional activation patterns across the cortical sheet. Applying unsupervised learning to the Allen Human Brain Atlas and Neurosynth databases, we identify a ventromedial–dorsolateral gradient of gene assemblies that separate affective and perceptual domains. This topographic molecular-psychological signature reflects the hierarchical organization of the neocortex, including systematic variations in cell type, myeloarchitecture, laminar differentiation and intrinsic network affiliation. In addition, this molecular-psychological signature strengthens over neurodevelopment and can be replicated in two independent repositories. Collectively, our results reveal spatially covarying transcriptomic and cognitive architectures, highlighting the influence that molecular mechanisms exert on psychological processes.
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The AHBA is available at https://human.brain-map.org/static/download. The Neurosynth database is available at https://neurosynth.org/. The HCP database is available at https://db.humanconnectome.org/data/projects/HCP_1200. The BrainSpan database is available at https://www.brainspan.org/static/download.html. Processed data as used in this report are available at https://github.com/netneurolab/hansen_genescognition. BrainMap data are available upon reasonable request to B.M.
Code used to conduct the reported analyses is available at https://github.com/netneurolab/hansen_genescognition.
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We thank V. Bazinet, L. Suarez, G. Shafiei, B. Vazquez-Rodriguez and Z.-Q. Liu for comments and suggestions on the manuscript. This research was undertaken thanks in part to funding from the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives initiative. B.M. acknowledges support from the Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant RGPIN 017-04265) and Canada Research Chairs Program. J.W.V. was funded by NIH grant T32MH019112. D.B. was supported by the Healthy Brains for Healthy Lives initiative (Canada First Research Excellence Fund), CIFAR Artificial Intelligence Chairs program (Canada Institute for Advanced Research), Google (Research Award) and NIH grant R01AG068563A. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
The authors declare no competing interests.
Peer review information Nature Human Behaviour thanks Andre Altmann, Håkon Grydeland and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Hansen, J.Y., Markello, R.D., Vogel, J.W. et al. Mapping gene transcription and neurocognition across human neocortex. Nat Hum Behav (2021). https://doi.org/10.1038/s41562-021-01082-z