Summary: Scientists have uncovered a biological “blueprint” that shows how the brain’s smallest building blocks create the large networks that drive thought, emotion, and behavior. By combining brain imaging with genetic and molecular data, the team demonstrated that cellular and chemical patterns directly shape functional brain networks.
The study reveals how microscopic features such as cell types, neurotransmitters, and energy systems actively bridge biology and cognition. These findings could transform how researchers understand aging, mental illness, and why some brains remain resilient later in life.
Key Facts
- Micro-to-Macro Link: Cellular and molecular patterns were directly connected to large-scale brain networks.
- Mental Health Insight: The same biological systems tied to thought and emotion are disrupted in disorders like schizophrenia and depression.
- Precision Medicine Potential: The findings could enable personalized treatments based on each person’s unique brain biology.
Source: Georgia State University
A new study from experts with Georgia State University has achieved a long-standing goal in neuroscience: showing how the brain’s smallest components build the systems that shape thought, emotion and behavior.
The research, published in the journal Nature Communications, could transform how scientists understand cognition and aging, as well as mental health disorders like depression and schizophrenia.
By combining brain scans with genetic data and molecular imaging, the researchers have uncovered a detailed biological map linking different levels of the brain and revealing the long-sought bridge between micro- and macro-level brain organization.
Vince Calhoun is a Distinguished University Professor with Georgia State and a Georgia Research Alliance Eminent Scholar with faculty appointments at Georgia Tech and Emory University. He leads the collaborative tri-institutional Center for Translational Research in Neuroimaging and Data Science, or TReNDS Center, and is a senior author on the study.
“We found that the brain’s large-scale networks are built on a hidden biological blueprint. By aligning data from cells, molecules and imaging, we showed that the same architecture seen in fMRI is rooted in cellular and molecular organization,” Calhoun said.
“Each dataset alone gives part of the story. Together, they reveal how chemical and cellular gradients actually help wire the brain’s networks.”
Calhoun said understanding this connection could help experts better understand mental health conditions and brain disorders. It could also offer new insights, like why some people stay sharp later in life and others don’t.
The research team combined brain scans that show how regions communicate over time. By capturing shifting patterns of activity called dynamic connectivity — with detailed maps of brain cells, chemical messengers like serotonin and dopamine, and energy-producing structures such as mitochondria — they were able to build a comprehensive picture of the brain’s inner workings.
Using a statistical technique called mediation analysis, the researchers showed that these networks don’t just correlate with biology and behavior — they actively bridge the two, helping explain how molecular features influence cognition.
Guozheng Feng, the study’s lead author and a postdoctoral research associate at the TReNDS Center, said the research reveals how certain brain networks act as middlemen, linking the microscopic biology of the brain (like specific cell types) to complex behaviors and mental processes.
“This study is bringing us closer to answering one of the most fundamental questions in neuroscience: how microscopic cellular and molecular foundations shape the brain’s networks which, in turn, give rise to complex thought, emotion and behavior,” Feng said.
“Many mental and neurodegenerative disorders involve both molecular imbalance and network disruption,” Calhoun added.
“This work shows these are linked. Understanding the biological foundation of networks could help us pinpoint which systems are most vulnerable in schizophrenia, depression or Alzheimer’s — and why.”
Jiayu Chen is a research assistant professor with the TReNDS Center who was part of the research team. Her work, using advanced brain scans, focuses on studying how genes influence the way the brain looks and works.
“This work helps answer a big question in neuroscience: How do cellular and molecular organizations underlie the architecture of functional brain networks, which influence the way we think, feel and behave?” Chen said. “We are now one step closer to those answers.”
Calhoun said the collaborative TReNDS Center is uniquely equipped for these kinds of discoveries. He hopes to ultimately create a “map” that links each person’s biology with how their brain networks function.
This could help doctors customize treatments specifically to their patients based on how their particular biology influences their brain’s networks.
The TReNDS Center, a partnership among Georgia State, Georgia Tech and Emory University, develops advanced tools to turn brain imaging data into meaningful biomarkers. Its goal is to improve understanding and treatment of brain health and disease.
Funding: This research was supported by funding from the National Science Foundation (NSF) under Grant #2112455 and the National Institutes of Health (NIH) through Grants #R01MH123610 and #R01MH136665.
Key Questions Answered:
A: Large-scale brain networks grow directly from microscopic cellular and molecular organization.
A: It directly linked genes, molecules, and brain activity into one continuous biological system.
A: It explains how molecular imbalances can disrupt brain networks in disorders like depression and schizophrenia.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this neuroscience, mood, memory, and behavior research news
Author: Noelle Reetz
Source: Georgia State University
Contact: Noelle Reetz – Georgia State University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Cellular and molecular associations with intrinsic brain organization” by Vince Calhoun et al. Nature Communications
Abstract
Cellular and molecular associations with intrinsic brain organization
Understanding how cellular and molecular architecture underpins the large-scale organization of human brain function is a central challenge in neuroscience.
By integrating transcriptomic (microarray and single-nucleus RNA-sequencing), molecular imaging, and neuroimaging datasets, we observe spatial correspondences indicating that the distributions of diverse cell types, neurotransmitter systems, and mitochondrial phenotypes align with intrinsic connectivity networks (ICNs).
These associations extend beyond local correspondence to reflect network-level structure: inter-ICN similarity networks derived from cellular and molecular profiles recapitulate static and dynamic patterns of functional network connectivity (FNC), mirroring canonical functional domains.
Mediation analyses reveal that specific ICNs mediate the relationship between microscale cell-type architecture and domain-specific cognitive processes, while FNCs capture mediating pathways linking cell-type and neurotransmitter similarity networks to cognitive organization.
Together, our findings show that the brain’s functional architecture systematically aligns with cellular and molecular organization, which may constrain functional network formation and contribute to the neural basis of cognition.
