# Evolutionary expansion of human cerebral cortex: spatial patterns and transcriptional correlates

> **NIH NIH F32** · WASHINGTON UNIVERSITY · 2024 · $73,828

## Abstract

Project Summary/Abstract
The human cerebral cortex supports extraordinary cognitive capacities, including unmatched social and
technological complexity, elaborate cultural traditions, and language. It also plays a central role in diverse brain
disorders that cause profound human suffering, including schizophrenia and Alzheimer's dementia, that may
have only limited analogs in non-human species. One key adaptation is the dramatic expansion of the cortical
sheet vs other primates, particularly in higher cognitive (association) areas. This expansion is not uniform, but it
has proven challenging to accurately map the degree of expansion in different regions and to determine the
relative contributions of expansion of evolutionarily conserved areas vs the emergence of new areas. Recent
methodological advances make it feasible to generate substantially more accurate cortical expansion maps than
heretofore possible. Evolutionary divergence in cortical organization presumably reflects changes in gene
expression patterns responsible for the differentiation of cortical areas and the determination of areal size.
Recent advances in spatially resolved single-cell transcriptomics have led to the discovery of hundreds of
putative cell types whose diversity is a critical substrate of brain evolution. In this proposal both sets of advances
will be leveraged to address both evolutionary expansion and transcriptomic cell type divergence in human vs
macaque cortex. The proposed analyses will be empowered by active collaboration with multiple consortia,
including the Non-human Primate Neuroimaging & Neuroanatomy Project (NHP-NNP), and the Human and
Mammalian Brain Atlas (HMBA), a facet of the BRAIN Initiative Cell Atlas Network. State-of-the-art interspecies
registration will be performed by integrating putative homologous regions, myelin maps, and resting state
networks to derive a substantially more accurate map of the evolutionary expansion of the cortex in macaque vs
human than has previously been reported. Comparing this map and other brain maps to patterns of transcription
in humans and macaques will allow testing of whether (1) evolutionary expansion has a distinct transcriptional
signature from other brain measures, (2) this signature is more evident in cell type distribution than in aggregate
gene expression, and (3) human-enriched cell types (e.g., in layer 4) play a prominent role in cortical expansion
and diversification. Accurately registered transcription and neuroimaging measures will provide new evidence
for distinguishing evolutionally emergent areas from conserved areas that have undergone evolutionary
expansion. Taken together, the proposed research will augment the translational potential of studies utilizing
non-human primate models, enhance our understanding of the areal and cellular substrates of the complex
behaviors, and provide new insights into possible mechanisms of primarily human mental and neurological
disorders.

## Key facts

- **NIH application ID:** 10997155
- **Project number:** 1F32MH138113-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Burke Quartman Rosen
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $73,828
- **Award type:** 1
- **Project period:** 2024-06-20 → 2027-06-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997155

## Citation

> US National Institutes of Health, RePORTER application 10997155, Evolutionary expansion of human cerebral cortex: spatial patterns and transcriptional correlates (1F32MH138113-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10997155. Licensed CC0.

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