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Mapping gene transcription and neurocognition across human neocortex

Abstract

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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Fig. 1: Relating gene expression to functional association.
Fig. 2: Gene sets underlying psychological processes.
Fig. 3: The gene expression–functional association gradient is organized around microscale and macroscale hierarchies.
Fig. 4: The molecular signature of psychological function strengthens with development.

Data availability

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 availability

Code used to conduct the reported analyses is available at https://github.com/netneurolab/hansen_genescognition.

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Acknowledgements

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.

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J.Y.H. and B.M. conceived of the study idea. J.Y.H. performed the formal analysis with contributions from R.D.M. R.D.M., J.W.V., J.S. and D.B. contributed data. J.Y.H. and B.M. wrote the manuscript with valuable revision by R.D.M., J.W.V., J.S. and D.B. B.M. was the project administrator.

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Correspondence to Bratislav Misic.

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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

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