Three-Dimensional Digital Reconstruction of the Cerebellar Cortex: Lobule Thickness, Surface Area Measurements, and Layer Architecture

Abstract

The cerebellum is ontogenetically one of the first structures to develop in the central nervous system; nevertheless, it has been only recently reconsidered for its significant neurobiological, functional, and clinical relevance in humans. Thus, it has been a relatively under-studied compared to the cerebrum. Currently, non-invasive imaging modalities can barely reach the necessary resolution to unfold its entire, convoluted surface, while only histological analyses can reveal local information at the micrometer scale. Herein, we used the BigBrain dataset to generate area and point-wise thickness measurements for all layers of the cerebellar cortex and for each lobule in particular. We found that the overall surface area of the cerebellar granular layer (including Purkinje cells) was 1,732 cm2 and the molecular layer was 1,945 cm2. The average thickness of the granular layer is 0.88 mm (± 0.83) and that of the molecular layer is 0.32 mm (± 0.08). The cerebellum (both granular and molecular layers) is thicker at the depth of the sulci and thinner at the crowns of the gyri. Globally, the granular layer is thicker in the lateral-posterior-inferior region than the medial-superior regions. The characterization of individual layers in the cerebellum achieved herein represents a stepping-stone for investigations interrelating structural and functional connectivity with cerebellar architectonics using neuroimaging, which is a matter of considerable relevance in basic and clinical neuroscience. Furthermore, these data provide templates for the construction of cerebellar topographic maps and the precise localization of structural and functional alterations in diseases affecting the cerebellum.

Diversity and evolution of cerebellar folding in mammals

“…The previous work of Sultan and Braitenberg (1993) is remarkable in this respect, providing beautiful representations of the unfolded cerebellar surface for 15 different species. However, their method produced smaller cerebellar surface areas than in the same species using a more precise method, suggesting that it underestimates the actual values (Sereno et al 2020, Zheng et al 2022), and hence the magnitude of cerebellar folding.…”

“…A finer understanding of the mesoscopic and macroscopic cerebellar neuroanatomical patterns would require more precise surface reconstructions in large numbers of species. The full reconstruction of the cerebellar surface is still challenging: to our knowledge, only 3 cerebella have been precisely reconstructed: 2 humans and 1 macaque (Sereno et al 2020, Zheng et al 2022). These two humans had markedly different cerebellar surface areas, one being >20% larger than the other, which highlight the necessity for increasing not only inter-individual precision, but also sample size.…”

“…Histological data, even at low scanning resolution, can provide sufficient information to distinguish folia as well as cerebellar cortical layers. However, data is only 2-D, and sectioning often induces non-trivial deformations which make it challenging to create full 3-D reconstructions (see, however, the work of Sereno et al 2020 and Zheng et al 2022). Using histological data Ashwell (2020) was able to estimate the surface area in 90 species of marsupials and 57 species of eutherian mammals, but did not study folia, of which the measurement remains challenging.…”

Variations on the theme: focus on cerebellum and emotional processing

“…On average, the granular layer is 73% thicker than the molecular layer ( Zheng et al, 2022 ), whereas the Purkinje cell layer is single cell thick. The difference in layer thickness constrains the area occupied by neurons on the parasagittal surface, e.g., size and width of PCs dendritic trees.…”

Primate Cerebellar Scaling in Connection to the Cerebrum: A 34-Species Phylogenetic Comparative Analysis

“…Within it, the ansiform area is characterized by strong positive allometry 13,130 , unique functional activations 14,15 and involvement in functional networks [16][17][18]42,43 . It furthermore has a distinct developmental trajectory 150 and structural properties 150,151 , and a characteristic role in disorders 7 . Concludingly, the ansiform area should be a primary area of interest for the study of human and comparative cognitive correlates in the future 7 .…”