Cytoarchitectural heterogeneity of the DMN. Credit: Nature Neuroscience (2025). DOI: 10.1038/s41593-024-01868-0
The default mode network (DMN) is a set of interconnected brain regions known to be most active when humans are awake but not engaged in physical activities, such as relaxing, resting or daydreaming. This brain network has been found to support a variety of mental functions, including introspection, memories of past experiences and the ability to understand others (i.e., social cognitions).
The DMN includes four main brain regions: the medial prefrontal cortex (mPFC), the posterior cingulate cortex (PCC), the angular gyrus and the hippocampus. While several studies have explored the function of this network, its anatomical structure and contribution to information processing are not fully understood.
Researchers at McGill University, Forschungszentrum Jülich and other institutes recently carried out a study aimed at better understanding the anatomy of the DMN, specifically examining the organization of neurons in the tissue of its connected brain regions, which is known as cytoarchitecture. Their findings, published in Nature Neuroscience, offer new indications that the DMN has a widespread influence on the human brain and its associated cognitive (i.e., mental) functions.
"The default mode network (DMN) is implicated in many aspects of complex thought and behavior," Casey Paquola, Margaret Garber and their colleagues wrote in their paper. "We leverage postmortem histology and in vivo neuroimaging to characterize the anatomy of the DMN to better understand its role in information processing and cortical communication."
To closely examine the anatomy of the DMN, Paquola, Garber and their colleagues used two main experimental approaches, known as post-mortem histology and in vivo neuroimaging. The first of these approaches entails the microscopic examination of brain tissue preserved from deceased patients, while the second involves scanning the brains of living individuals.
"Our results show that the DMN is cytoarchitecturally heterogenous, containing cytoarchitectural types that are variably specialized for unimodal, heteromodal and memory-related processing," wrote Paquola, Garber and their colleagues. "Studying diffusion-based structural connectivity in combination with cytoarchitecture, we found the DMN contains regions receptive to sensory cortex input and a core relatively insulated from environmental input."
By mapping white matter pathways in the human brain, the researchers learned more about the organization and structure of the DMN. Specifically, they found that this network is made up of brain regions that receive sensory inputs and a "core" that is relatively "shielded" from the outside world (i.e., does not receive many external inputs).
"Finally, analysis of signal flow with effective connectivity models showed that the DMN is unique among cortical networks in balancing its output across the levels of sensory hierarchies," wrote Paquola, Garber and their colleagues. "Together, our study establishes an anatomical foundation from which accounts of the broad role the DMN plays in human brain function and cognition can be developed."
This recent study by Paquola, Garber and their colleagues could significantly advance the present understanding of the DMN, offering valuable insight about its cytoarchitecture, the connections between its underlying brain structures, and how it contributes to mental functions. The researchers' findings and the anatomical framework they introduced could inspire further research into this crucial brain network, which could shed new light on its contribution to healthy cognitive function, and specific mental health disorders.
More information: Casey Paquola et al, The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow, Nature Neuroscience (2025). DOI: 10.1038/s41593-024-01868-0.
Journal information: Nature Neuroscience
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