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@PHDTHESIS{Saberi:1043058,
      author       = {Saberi, Amin},
      title        = {{C}omputational {A}nalysis of {M}ultiscale {C}ortical
                      {O}rganization and {D}evelopment},
      school       = {Heinrich-Heine-Universität Düsseldorf},
      type         = {Dissertation},
      reportid     = {FZJ-2025-02750},
      pages        = {42},
      year         = {2025},
      note         = {Dissertation, Heinrich-Heine-Universität Düsseldorf,
                      2025},
      abstract     = {The cerebral cortex is organized at multiple scales,
                      ranging from ion channels, to neuronal circuitsorganized
                      across cortical layers, to the interconnected network of
                      cortical areas. The structuraland functional properties at
                      these scales vary widely across cortical areas. This
                      heterogeneousorganization across different scales is the
                      result of continuous refinement throughout the
                      lifespan.Understanding the multiscale organization of the
                      cerebral cortex and its maturation requiresintegrative
                      computational approaches that bridge across scales. The goal
                      of this work was to useadvanced computational techniques to
                      better understand how micro- and mesoscale corticalphenomena
                      relate to macroscale cortical organization throughout
                      development. Specifically,we examined cortical
                      cytoarchitecture associated with corticocortical
                      connectivity (Study1), cortical microcircuitry inferred from
                      functional dynamics and connectivity (Study 2),and cellular
                      and molecular processes underlying cortical morphology
                      (Study 3).In Study 1, we found that cortical laminar
                      structure at the mesoscale varied along a principalaxis
                      extending from caudal to rostral areas, along which the
                      relative thickness of deeper layersincreased. This axis was
                      co-aligned with the hierarchical organization of macroscale
                      corticalconnectivity. Furthermore, similarity of laminar
                      structure was associated with the likelihoodand strength of
                      corticocortical connectivity, a phenomenon thought to have
                      developmental roots.Next, in Study 2, we used an
                      individualized computational modeling approach to infer
                      theregional levels of excitation-inhibition balance in
                      cortical microcircuits of developing adolescentsbased on
                      their macroscale cortical connectivity and dynamics observed
                      in resting-state functionalimaging. To enable the
                      large-scale simulations required for this approach, we
                      developed a noveland efficient implementation of the
                      simulations, released as a Python package, cuBNM. Usingthis
                      approach, across two independent cross-sectional and
                      longitudinal datasets, we found awidespread age-related
                      decrease of excitation relative to inhibition within the
                      association areas,paralleled by its increase or lack of
                      change in sensorimotor areas. This developmental patternwas
                      consistent with the previously proposed
                      sensorimotor-association spatiotemporal pattern
                      ofneurodevelopment.Finally, in study 3, we examined the
                      spatial co-localization between cortical maps of
                      microandmesoscale neurobiological processes with
                      cross-sectional and longitudinal spatiotemporalpatterns of
                      cortical thickness changes across the lifespan to understand
                      which cellular andmolecular processes may underlie
                      maturation and lifespan changes in cortical morphology at
                      themacroscale. Our results suggest that processes such as
                      dopaminergic, glutamatergic, and cholinergicneurotransmitter
                      systems, as well as glial cells, inhibitory neurons, and
                      brain metabolism,may contribute to the maturation of
                      cortical morphology.Overall, this work advances our
                      understanding of multiscale cortical organization and
                      itsmaturation while contributing to the development of
                      computational tools for future research.By integrating
                      micro-, meso-, and macroscale perspectives, our findings on
                      normative cortical organizationand maturation provide a
                      foundation for investigating impaired cortical developmentin
                      mental health disorders.ii},
      cin          = {INM-7},
      cid          = {I:(DE-Juel1)INM-7-20090406},
      pnm          = {5252 - Brain Dysfunction and Plasticity (POF4-525) / 5251 -
                      Multilevel Brain Organization and Variability (POF4-525)},
      pid          = {G:(DE-HGF)POF4-5252 / G:(DE-HGF)POF4-5251},
      typ          = {PUB:(DE-HGF)11},
      doi          = {10.34734/FZJ-2025-02750},
      url          = {https://juser.fz-juelich.de/record/1043058},
}