Integration across biophysical scales identifies molecular and cellular correlates of person-to-person variability in human brain connectivity

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2240-2252
Number of pages13
JournalNature Neuroscience
Volume27
Issue number11
DOIs
Publication statusPublished - 2024 Nov

Subject classification (UKÄ)

  • Neurosciences

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