Integration across biophysical scales identifies molecular and cellular correlates of person-to-person variability in human brain connectivity
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.
Authors
- Hamad M. Muhammad (ORCID: https://orcid.org/0000-0003-0713-117X)
- Shinya Tasaki (ORCID: https://orcid.org/0000-0003-3656-7394)
- Jeremy H. Herskowitz (ORCID: https://orcid.org/0000-0002-7227-1470)
- David Alan Bennett (ORCID: https://orcid.org/0000-0003-3689-554X)
- Courtney K. Walker (ORCID: https://orcid.org/0000-0002-7826-4044)
- Audrey J. Weber (ORCID: https://orcid.org/0000-0003-1851-941X)
- Nicholas T. Seyfried (ORCID: https://orcid.org/0000-0002-4507-624X)
- Julia P. Andrade
- Ashley Adamson (ORCID: https://orcid.org/0000-0001-6231-6279)
- Theodore Daniel Satterthwaite (ORCID: https://orcid.org/0000-0001-7072-9399)
- Kendall A. Curtis (ORCID: https://orcid.org/0000-0002-2450-636X)
- Sydney Covitz (ORCID: https://orcid.org/0000-0002-7430-4125)
- Jakob Seidlitz (ORCID: https://orcid.org/0000-0002-8164-7476)
- Matthew Cieslak (ORCID: https://orcid.org/0000-0002-1931-4734)
- Bernard Ng (ORCID: https://orcid.org/0000-0002-8688-3873)
- Emily H. Poovey
- Kelsey M. Greathouse (ORCID: https://orcid.org/0000-0002-4045-8708)
- Chris Gaiteri (ORCID: https://orcid.org/0000-0001-7838-8664)
- Jacob W. Vogel (ORCID: https://orcid.org/0000-0001-6394-9940)
- Ada Zhang (ORCID: https://orcid.org/0000-0003-4013-1657)
Institutions
- Rush University Medical Center (US)
- Children's Hospital of Philadelphia (US)
- Emory University (US)
- Lund University (SE)
- SUNY Upstate Medical University (US)
- Science for Life Laboratory (SE)
- University of Alabama at Birmingham (US)
- Lifespan (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Neuroscience
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1038/s41593-024-01788-z
- Citations
- 14
- Primary Topic
- Functional Brain Connectivity Studies
- Type
- article
- Field-Weighted Citation Impact
- 4.80
Funders
- National Institutes of Health