A Molecular Basis of Human Brain Connectivity

Bernard Ng; Shinya Tasaki; Kelsey M. Greathouse; Courtney K. Walker; Ada Zhang; Sydney C. Covitz; Matthew Cieslak; Ashley B. Adamson; Julia P. Andrade; Emily H. Poovey; Kendall A. Curtis; Hamad M. Muhammad; Jakob Seidlitz; Theodore Daniel Satterthwaite; David Alan Bennett; Nicholas T. Seyfried; Jacob W. Vogel; Chris Gaiteri; Jeremy H. Herskowitz

doi:10.1101/2023.07.20.549895

NeurosciencebioRxivJul 20, 2023

Preprint

A Molecular Basis of Human Brain Connectivity

Bernard Ng iD, Shinya Tasaki iD, Kelsey M. Greathouse iD, Courtney K. Walker iD, Ada Zhang iD, Sydney C. Covitz iD, Matthew Cieslak iD, Ashley B. Adamson iD, Julia P. Andrade, Emily H. Poovey, Kendall A. Curtis iD, Hamad M. Muhammad iD, Jakob Seidlitz iD, Theodore Daniel Satterthwaite iD, David Alan Bennett iD, Nicholas T. Seyfried iD, Jacob W. Vogel iD, Chris Gaiteri iD, Jeremy H. Herskowitz iD

Abstract

Neuroimaging is commonly used to infer human brain connectivity, but those measurements are far-removed from the molecular underpinnings at synapses. To uncover the molecular basis of human brain connectivity, we analyzed a unique cohort of 98 individuals who provided neuroimaging and genetic data contemporaneous with dendritic spine morphometric, proteomic, and gene expression data from the superior frontal and inferior temporal gyri. Through cellular contextualization of the molecular data with dendritic spine morphology, we identified hundreds of proteins related to synapses, energy metabolism, and RNA processing that explain between-individual differences in functional connectivity and structural covariation. By integrating data at the genetic, molecular, subcellular, and tissue levels, we bridged the divergent fields of molecular biology and neuroimaging to identify a molecular basis of brain connectivity. One-Sentence SummaryDendritic spine morphometry and synaptic proteins unite the divergent fields of molecular biology and neuroimaging.

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