BigBrain 3D atlas of cortical layers: Cortical and laminar thickness gradients diverge in sensory and motor cortices

Abstract

Histological atlases of the cerebral cortex, such as those made famous by Brodmann and von Economo, are invaluable for understanding human brain microstructure and its relationship with functional organization in the brain. However, these existing atlases are limited to small numbers of manually annotated samples from a single cerebral hemisphere, measured from 2D histological sections. We present the first whole-brain quantitative 3D laminar atlas of the human cerebral cortex. It was derived from a 3D histological atlas of the human brain at 20-micrometer isotropic resolution (BigBrain), using a convolutional neural network to segment, automatically, the cortical layers in both hemispheres. Our approach overcomes many of the historical challenges with measurement of histological thickness in 2D, and the resultant laminar atlas provides an unprecedented level of precision and detail. We utilized this BigBrain cortical atlas to test whether previously reported thickness gradients, as measured by MRI in sensory and motor processing cortices, were present in a histological atlas of cortical thickness and which cortical layers were contributing to these gradients. Cortical thickness increased across sensory processing hierarchies, primarily driven by layers III, V, and VI. In contrast, motor-frontal cortices showed the opposite pattern, with decreases in total and pyramidal layer thickness from motor to frontal association cortices. These findings illustrate how this laminar atlas will provide a link between single-neuron morphology, mesoscale cortical layering, macroscopic cortical thickness, and, ultimately, functional neuroanatomy.

CIVET-Macaque: an automated pipeline for MRI-based cortical surface generation and cortical thickness in macaques

“…These include thinner somatosensory, visual and auditory areas, thicker temporal pole and motor cortex, with the remaining homotypic isocortex exhibiting thicknesses in between these extremes . This pattern is consistent with existing studies of macaque MRI morphology (Wagstyl et al 2015) and similar to patterns seen in human histological studies of cortical thickness in the human BigBrain (Amunts et al 2013;Wagstyl et al 2020) . CIVET-macaque would be an essential step towards creating an equivalent 3D histological atlas of the macaque brain.…”

“…Surfaces can be aligned to a common average template, enabling group-comparison studies, and surface-based parcellations such as atlases can be mapped to individual surface meshes for regional analyses, with per-vertex correspondence between the white matter and pial surfaces. Furthermore, coregistering other imaging modalities to the same space enables quantitative sampling of any number of in vivo modalities: fMRI, qMRI, PET, EEG, MEG (Weiskopf et al 2013;Greve et al 2014;Bonaiuto et al 2018;Yeo et al 2011) , as well as post mortem histological (Wagstyl et al 2020) and g enetic data (Hawrylycz et al 2012) . Once sampled to the mesh, and coregistered to a common template, vertex-based representations allow for intermodal analysis and application of more complex analytical techniques.…”

“…For instance, in humans, surface analysis has been used to parcellate the cortex according to multimodal in vivo data from task and resting state fMRI and structural images in the same subjects (Glasser et al 2016) . Radial sampling between gray and white cortical surfaces across the cortex can produce depth-dependent intensity profiles that, with sufficient resolution and contrast, can be used to segment cortical layers (Wagstyl et al 2020) . Surface-based descriptions have also been used to characterize human semantic organization (Huth et al 2016) and pathology .…”

Topographic gradients of intrinsic dynamics across neocortex

“…An emerging literature emphasizes the hierarchical organization of neural systems, whereby systematic variations in laminar architecture across the cortical sheet are mirrored by multiple cytological properties, including neuron density, spine count, branching and neurotransmitter receptor profiles [47,63,65]. These variations ultimately manifest as spatially ordered gradients of structural and functional attributes [50], including gene expression [12,31], cortical thickness [100], intracortical myelin [49], laminar differentiation [72,99] and excitability [22,64,88,102]. Indeed, we find that the two patterns of intrinsic dynamics are closely related to gene expression, intracortical myelin and cortical thickness.…”

Closing the gap from transcription to the structural connectome enhances the study of connections in the human brain

“…The grey matter of the cortex is composed of six layers or so across mammals and consists of neuronal and glial cell bodies. 62 Neurons exhibit stereotypic patterns of projections depending on where their soma are located across the depth of the cortex. A number of studies have employed anatomical tracers to investigate patterns of connectivity across several mammalian species in adults and in development.…”