Integration Across Biophysical Scales Identifies Molecular and Cellular Correlates of Person-to-Person Variability in Human Brain Connectivity

Authors

• Bernard Ng
• Shinya Tasaki
• Kelsey M Greathouse
• Courtney K Walker
• Ada Zhang
• Sydney Covitz
• Matt Cieslak
• Audrey J Weber
• Ashley B Adamson
• Julia P Andrade
• Emily H Poovey
• Kendall A Curtis
• Hamad M Muhammad
• Jakob Seidlitz
• Ted Satterthwaite
• David A Bennett
• Nicholas T Seyfried
• Jacob Vogel
• Chris Gaiteri
• Jeremy H Herskowitz

Language

English

Publication Date

11-1-2024

Journal

Nature Neuroscience

DOI

10.1038/s41593-024-01788-z

PMID

39482360

PMCID

PMC11537986

PubMedCentral® Posted Date

10-31-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Brain connectivity arises from interactions across biophysical scales, ranging from molecular to cellular to anatomical to network level. To date, there has been little progress toward integrated analysis across these scales. To bridge this gap, from a unique cohort of 98 individuals, we collected antemortem neuroimaging and genetic data, as well as postmortem dendritic spine morphometric, proteomic and gene expression data from the superior frontal and inferior temporal gyri. Through the integration of the molecular and dendritic spine morphology data, we identified hundreds of proteins that explain interindividual differences in functional connectivity and structural covariation. These proteins are enriched for synaptic structures and functions, energy metabolism and RNA processing. By integrating data at the genetic, molecular, subcellular and tissue levels, we link specific biochemical changes at synapses to connectivity between brain regions. These results demonstrate the feasibility of integrating data from vastly different biophysical scales to provide a more comprehensive understanding of brain connectivity.

Keywords

Humans, Female, Male, Brain, Adult, Middle Aged, Dendritic Spines, Connectome, Synapses, Proteomics, Nerve Net, Aged, Neural Pathways, Young Adult, Cellular neuroscience, Network models, Genetics of the nervous system, Functional magnetic resonance imaging

Published Open-Access

yes

Recommended Citation

Ng, Bernard; Tasaki, Shinya; Greathouse, Kelsey M; et al., "Integration Across Biophysical Scales Identifies Molecular and Cellular Correlates of Person-to-Person Variability in Human Brain Connectivity" (2024). Faculty, Staff and Student Publications. 939.
https://digitalcommons.library.tmc.edu/uthshis_docs/939