# Connecting the mechanobiology of tissue and cells in cerebral cortical folding

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $499,698

## Abstract

ABSTRACT
The folding patterns observed in the cerebral cortex of individuals affected by many neurodevelopmental
disorders differ from those in typically-developing "control" individuals. The human cerebral cortex folds over
the period from the middle of gestation through the first months of postnatal life. Although much is known about
how the brain develops over this time period, including proliferative activity, morphological maturation of many
cell types, establishment of synaptic connections, development of cortical circuitry, macroscopic growth, and
system-level physiological changes in the brain, relatively little is understood about how these changes relate
to the production of a normal, or abnormal, folding pattern at maturity. Shortcomings in our understanding of
the relationship between cellular-level developmental events and macroscopic behavior (growth and
biomechanical properties of tissue) limit our ability to explain a given folding abnormality in terms of its
neurodevelopmental source, or in terms of potential etiological factors important for a specific
neurodevelopmental disorder. This application proposes a series of studies to link high-precision experimental
measures of brain growth and mechanical properties with computational simulations to advance our
understanding of the biomechanical factors that influence cerebral cortical folding. This combined experimental
and theoretical approach will be used to analyze folding of the ferret cerebral cortex. As with the human brain,
the ferret brain possesses gyri and sulci at maturity, but in contrast to humans, these folds arise postnatally in
ferrets. Specific focus will be placed on the occipital temporal sulcus (OTS), within the primary visual cortex,
which folds relatively late compared to other sulci, concluding by P35. Recently, we have discovered that OTS
formation is severely affected (or that the OTS does not form at all) in ferrets that have undergone bilateral
enucleation at P7. Growth and mechanical properties will therefore be characterized in sighted control (SC)
and bilaterally enucleated on P7 (BEP7) ferrets at 6 time points ranging from P8 through P38. This data will be
integrated with the development of a multiscale theoretical and computational model of brain growth. In Aim 1,
growth will be characterized on a macroscopic scale by in vivo MRI, and on a cellular level by measuring how
P7 enucleation affects proliferation dynamics and changes cell body and neuropil volumes over the period of
cortical folding. In Aim 2, mechanical properties of the tissue will be quantified over the same age range. Shear
moduli of cortical gray matter and developing white matter will be determined using atomic force microscopy.
Tissue stress will be measured by observing tissue deformations following incisions. Tissue stress on a smaller
spatial scale will be inferred from the shapes of nuclei and from the orientation distributions of cellular
processes. In Aim 3, the experimental da...

## Key facts

- **NIH application ID:** 9970558
- **Project number:** 5R01NS111948-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** PHILIP V BAYLY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $499,698
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970558

## Citation

> US National Institutes of Health, RePORTER application 9970558, Connecting the mechanobiology of tissue and cells in cerebral cortical folding (5R01NS111948-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9970558. Licensed CC0.

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