Animal studies of neurodevelopment have shown that recordings of intrinsic cortical activity evolve from synchronized and high amplitude to sparse and low amplitude as plasticity declines and the cortex matures. Leveraging resting-state functional MRI (fMRI) data from 1,033 youths (ages 8–23 years), we find that this stereotyped refinement of intrinsic activity occurs during human development and provides evidence for a cortical gradient of neurodevelopmental change. Declines in the amplitude of intrinsic fMRI activity were initiated heterochronously across regions and were coupled to the maturation of intracortical myelin, a developmental plasticity regulator. Spatiotemporal variability in regional developmental trajectories was organized along a hierarchical, sensorimotor–association cortical axis from ages 8 to 18. The sensorimotor–association axis furthermore captured variation in associations between youths’ neighborhood environments and intrinsic fMRI activity; associations suggest that the effects of environmental disadvantage on the maturing brain diverge most across this axis during midadolescence. These results uncover a hierarchical neurodevelopmental axis and offer insight into the progression of cortical plasticity in humans.
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The current study analyzes an existing, publicly available dataset from the Philadelphia Neurodevelopmental Cohort, available in the Database of Genotypes and Phenotypes (phs000607.v3.p2). Study analyses additionally made use of publicly available cortical atlases, including the HCP-MMP atlas (downloaded from https://github.com/PennLINC/xcp_d/blob/main/xcp_d/data/ciftiatlas/glasser_space-fsLR_den-32k_desc-atlas.dlabel.nii), the Schaefer-400 atlas (downloaded from https://github.com/PennLINC/xcp_d/blob/main/xcp_d/data/ciftiatlas/Schaefer2018_400Parcels_17Networks_order.dlabel.nii) and the S–A axis (downloaded from https://pennlinc.github.io/S-A_ArchetypalAxis/). Data derivatives from the current study, including development effect and environment effect maps, are available for download from https://doi.org/10.5281/zenodo.7606653.
Neuroimaging data were processed with containerized software packages available on dockerhub. Resting-state fMRI data were processed with fMRIPrep 20.2.3 (https://hub.docker.com/r/nipreps/fmriprep/tags) and xcp_d 0.0.4 (https://hub.docker.com/r/pennlinc/xcp_abcd/tags). Following image processing, all subsequent analyses and statistics were conducted in R 4.0.2 (https://www.r-project.org) using original analysis code and Connectome Workbench 1.5.0 tools (https://www.humanconnectome.org/software/get-connectome-workbench). Original code, including code used to calculate regional fluctuation amplitude, fit regional GAMs, contextualize developmental and environmental effects and perform sensitivity analyses, has been deposited at Zenodo and is available at https://doi.org/10.5281/zenodo.7606653. A detailed description of the code and guide to code implementation is additionally provided at https://pennlinc.github.io/spatiotemp_dev_plasticity/.
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This study was supported by grants from the National Institute of Health: R01MH113550 to T.D.S. and D.S.B., R01MH120482 to T.D.S., R01MH112847 to R.T.S. and T.D.S., R01MH119219 to R.C.G. and R.E.G., R01MH123563 to R.T.S., R01MH119185 to D.R.R., R01MH120174 to D.R.R., R01NS060910 to R.T.S., R01EB022573 to T.D.S., RF1MH116920 to T.D.S. and D.S.B., RF1MH121867 to T.D.S., R37MH125829 to T.D.S., R34DA050297 to A.P.M., K08MH120564 to A.F.A.-B., K99MH127293 to B.L. and T32MH014654 to J.S. V.J.S. was supported by a National Science Foundation Graduate Research Fellowship (DGE-1845298). The Philadelphia Neurodevelopmental Cohort was supported by RC2 grants MH089983 and MH089924. Additional support was provided by the Penn-CHOP Lifespan Brain Institute and the Penn Center for Biomedical Image Computing and Analytics.
The authors declare the following competing interest: R.T.S. receives consulting income from Octave Bioscience for work wholly unrelated to the present research. All other authors declare no competing interests.
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Sydnor, V.J., Larsen, B., Seidlitz, J. et al. Intrinsic activity development unfolds along a sensorimotor–association cortical axis in youth. Nat Neurosci 26, 638–649 (2023). https://doi.org/10.1038/s41593-023-01282-y