Scientists create a new map of the developing cerebral cortex

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Scientists at UNC School of Medicine have mapped the surface of the young human brain’s cortex with unprecedented resolution, revealing the development of key functional regions from two months before birth to two years after.

The new mapping of cortical development, reported online in the Proceedings of the National Academy of Sciencesrepresents a valuable resource for future research on brain development and offers a powerful new approach to the study of brain development conditions such as autism and schizophrenia.

“These findings provide an important benchmark for exploring and understanding the dynamics of early brain development,” said study lead author Gang Li, PhD, associate professor of radiology at UNC School of Medicine.

The study’s first author was Ying Huang, a doctoral candidate in Li’s lab.

The cortex is a sheet of brain cells that envelops much of the rest of the brain. The most evolutionarily advanced region of the brain, it is proportionally larger in humans than in other mammals, and is responsible for higher, typically human functions, including linguistic abilities and abstract reasoning.

The third trimester of pregnancy through the first two years of life is the most dynamic period of cortical development. The cortex thickens markedly during this interval and grows at an even faster rate in area terms, forming intricate cortical folds.

Disturbances of cortical thickening and expansion in this phase have been linked to autism and schizophrenia. However, neuroscientists do not have as detailed an understanding of this phase of development as they would like. In particular, they needed more comprehensive, high-resolution mapping, across the fetal to toddler age range, that divides or “particles” the developing cortex into distinct regions with their own rates of growth – especially surface Growth rates.

In the study, Li and his colleagues performed such mapping. They first collected a set of 1,037 high-quality magnetic resonance imaging (MRI) scans of infants in the age range of third trimester to two years. The scans came from two other research projects, the UNC/UMN Baby Connectome Project (BCP) and the Developing Human Connectome Project. The team analyzed the scan data using state-of-the-art computerized image processing methods, essentially dividing the cortical surface into a virtual mesh containing thousands of tiny circular areas and calculating the rate of surface expansion for each of these areas. .

The analysis did not begin with assumptions about the locations of brain structures or functional regions, but this regionalization of the brain became evident from the resulting maps, based solely on the different rates at which areas of the surface developed. In all, the researchers defined 18 distinct regions, which they found correlated well with what is already known about the functional regions of the developing cortex.

“All of these regions show dramatic surface expansion during this window of development, with each region having a distinct trajectory,” Li said.

The maps revealed that each region tended to have the same developmental path as its counterpart in the opposite hemisphere of the cortex. Gender differences were also apparent. Even controlling for sex differences in overall surface area—male brains having greater surface area—there were still differences in several regions. For example, the medial prefrontal region of the left hemisphere, thought to house important functions such as attention and working memory, became proportionally larger in males at the start of the second year of postnatal life.

The analysis also showed that patterns of cortical surface expansion during this early period of life were very different from developmental patterns of cortical thickness, suggesting that these two measures of brain development involve separate mechanisms.

Overall, Li said, the mapping provides fundamental new information about brain development.

He and his team now plan to extend this approach with MRI datasets that start at earlier ages and end at older ages. They also hope to eventually study analysis datasets covering children with the autism spectrum or other neurodevelopmental conditions. Such analyzes could offer not only clues to the origins of these conditions, but also the identification of early signs or biomarkers, which could in the future be used to administer earlier and more effective treatments.

The PNAS article titled “Mapping Developmental Regionalization and Cortical Surface Patterns from 29 Postmenstrual Weeks to 2 Years” was co-authored by Ying Huang, Zhengwang Wu, Fan Wang, Dan Hu, Tengfei Li, Lei Guo, Li Wang, Weili Lin, and Gang Li. At UNC-Chapel Hill, BCP MRIs were performed at the UNC Biomedical Research Imaging Center (BRIC), led by Weili Lin, PhD.

Funding was provided by the National Institutes of Health (MH116225, MH117943, MH109773, MH123202, 1U01MH110274) and the UNC/UMN Baby Connectome Project Consortium.

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