Regional patterns of human cortex development correlate with underlying neurobiology

Area of Science:

• Neuroscience
• Developmental Biology
• Computational Biology

Background:

• Human brain morphology changes significantly across the lifespan.
• Normative models track brain development, but biological mechanisms remain poorly understood.

Purpose of the Study:

• To investigate the molecular and cellular underpinnings of human cortical thickness development and aging.
• To link population-level brain organization patterns to individual developmental trajectories.

Main Methods:

• Utilized normative modeling and population neuroimaging.
• Integrated neurobiological brain atlases with lifespan models of cortical thickness.
• Analyzed spatial distributions of molecular and cellular features (e.g., neurotransmitter receptors, neurons, glial cells).
• Validated findings using longitudinal data from over 8,000 adolescents.

Main Results:

• Cortical thickness trajectories during childhood and adolescence are explained by dopaminergic receptors, inhibitory neurons, glial cells, and metabolic features (up to 50% variance).
• Adult cortical thickness changes are best explained by cholinergic and glutamatergic neurotransmitter systems.
• These relationships are supported by developmental gene expression and generalize to individual longitudinal data (up to 59% cohort-level, 18% single-subject level).

Conclusions:

• Human brain development and aging trajectories are intrinsically linked to molecular and cellular organization.
• Integrating neurobiological atlases with normative modeling offers a biologically meaningful approach to studying brain changes in vivo.
• This approach enhances understanding of the biological mechanisms driving lifespan brain morphology changes.