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@INPROCEEDINGS{Lotter:1014626,
      author       = {Lotter, Leon and Saberi, Amin and Jansen, Justine Y. and
                      Misic, Bratislav and Barker, Gareth J. and Bokde, Arun L. W.
                      and Desrivíeres, Sylvane and Flor, Herta and Grigis,
                      Antoine and Garavan, Hugh and Gowland, Penny and Heinz,
                      Andreas and Brühl, Rüdiger and Martinot, Jean-Luc and
                      Paillére, Marie-Paure and Artiges, Eric and Orfanos,
                      Dimitri Papadopoulos and Paus, Tomáš and Poustka, Luise
                      and Hohmann, Sarah and Fröhner, Juliane H. and Smolka,
                      Michael N. and Vaidya, Nilakshi and Walter, Henrik and
                      Whelan, Robert and Schumann, Gunter and Nees, Frauke and
                      Banaschewski, Tobias and Eickhoff, Simon and Dukart,
                      Jürgen},
      title        = {{H}uman cortex development is shaped by molecular and
                      cellular brain systems},
      reportid     = {FZJ-2023-03331},
      year         = {2023},
      abstract     = {Introduction:Human cerebral cortex morphology is subject to
                      complex developmental changes, with developmental
                      trajectories varying across brain regions (Bethlehem et al.,
                      2022; Rutherford et al., 2022). Several biological factors
                      influencing cortical thickness (CT) development have been
                      discussed, but naturally, human data are scarce. As
                      especially neurodevelopmental disorders are characterized by
                      atypical cortex development (Bethlehem et al., 2020;
                      Rutherford et al., 2022), knowledge about drivers of typical
                      development may shed light on the pathophysiology of
                      deviating neurodevelopment. In this study, we demonstrate
                      that population-average and single-subject CT trajectories
                      colocalize with, and are explained by, spatial distributions
                      of brain metabolism and immunity features, neurotransmitter
                      systems, cortical myelin, as well as neuronal and glial cell
                      populations. We provide novel information on human cortex
                      development within a framework that facilitates easy
                      transfer to new cohorts, paving the way for individualized
                      and biologically interpretable brain-based
                      biomarkers.Methods:We included 49 atlases of molecular and
                      cellular brain systems derived from healthy adult data
                      (Hansen et al., 2022; Dukart et al., 2021; Hawrylycz et al.,
                      2012). Atlases were parcellated in 148 bilateral cortex
                      regions and reduced to 18 factors (factor analysis retaining
                      dimensions explaining ≥ $1\%$ of variance). First, we
                      extracted 50th percentile "representative" CT data from a
                      normative CT model estimated on 58,836 subjects from 82
                      sites (5-90 years) (Rutherford et al., 2022). To test for
                      relationships between CT change patterns and multilevel
                      brain systems, we (i) estimated the spatial colocalization
                      (Spearman's ρ) between each factor and CT at each timepoint
                      (Vidal-Pineiro et al., 2020) and (ii) fitted multivariate
                      linear models "predicting" CT change from the multilevel
                      factors using a sliding window approach (5-year-steps). The
                      results were validated in longitudinal CT data from the ABCD
                      (n = 6,315; 20 sites; ~10-12 years; Casey et al., 2018) and
                      IMAGEN (n = 985-1177; 8 sites; ~14-22 years; Schumann et
                      al., 2010) cohort studies. Analyses were performed with
                      JuSpyce (Lotter and Dukart, 2022), a toolbox for large-scale
                      spatial association analyses, using strict spatial
                      autocorrelation-preserving permutation testing and false
                      discovery rate correction.Results:Spatial Spearman
                      colocalization analyses between cross-selctional CT and
                      biological brain systems revealed diverse colocalization
                      trajectories with a general pattern of strongest changes in
                      early and late phases of life. The combined biological
                      systems at molecular and cellular levels explained up to
                      $54\%$ of the spatial variance in modeled CT changes across
                      the lifespan with peaks at about 20-35 (molecular) and 15-20
                      (cellular) years of age, respectively. Subsequent analyses
                      accounting for shared variance showed that the 9 strongest
                      associated brain systems jointly explained up to $58\%$ of
                      CT change. Of particular relevance for early cortex
                      development were D1/2 dopaminergic receptors, microglia, and
                      somatostatin-expressing interneurons, while dopaminergic and
                      cholinergic neurotransmission was associated with midlife CT
                      maturation patterns. Normative model-based results
                      replicated in single-subject data, albeit showing
                      considerably higher variance (cohort-average R2 = $25-56\%;$
                      individual R2 $9-18\%,$ range $0-59\%).Conclusions:Factors$
                      shaping human brain morphology over the lifespan are poorly
                      understood. Here we demonstrate that the complex patterns in
                      which the human cerebral cortex develops and matures
                      colocalize with specific biological systems on molecular and
                      cellular levels. Our findings support roles of the
                      dopaminergic system, microglia and somatostatin-expressing
                      interneurons in early CT development, whereas cholinergic
                      and dopaminergic neurotransmission are associated with CT
                      changes across adulthood. Our results not only have
                      implications for the study of typical neurodevelopment, but
                      also hold promise for the value of neurodevelopmental
                      cross-modal association analyses for future clinical
                      research applications.},
      month         = {Jul},
      date          = {2023-07-21},
      organization  = {Organization for Human Brain Mapping
                       (OHBM), Montreal (Canada), 21 Jul 2023
                       - 26 Jul 2023},
      subtyp        = {After Call},
      cin          = {INM-7},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {5252 - Brain Dysfunction and Plasticity (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5252},
      typ          = {PUB:(DE-HGF)24},
      doi          = {10.34734/FZJ-2023-03331},
      url          = {https://juser.fz-juelich.de/record/1014626},
}