Exploration of the Architecture of the Human Default Mode Network: A Study Based on Cytoarchitecture, Wiring, and Signal Flow

Academic Background

The Default Mode Network (DMN) is a set of brain regions that are highly active during resting states, primarily distributed across the frontal, temporal, and parietal lobes. The DMN plays a crucial role in complex human thought and behavior, particularly in internally oriented cognitive tasks such as self-referential thinking, memory retrieval, and future planning. However, despite the widespread recognition of the functional importance of the DMN, its internal structure and mechanisms of information processing remain unclear. Previous studies have mainly focused on the functional connectivity of the DMN, but there is still a lack of in-depth understanding of its specific cytoarchitectural and neural connectivity features. To better explain the role of the DMN in information processing and cortical communication, researchers decided to combine postmortem histology and in vivo neuroimaging techniques to explore the anatomical structure of the DMN.

Source of the Paper

This research paper, titled “The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow,” was co-authored by Casey Paquola, Margaret Garber, Stefan Frässle, and other scholars. The research team comes from several internationally renowned institutions, including the Montreal Neurological Institute at McGill University in Canada and the Forschungszentrum Jülich in Germany. The paper was published online in the journal Nature Neuroscience on December 6, 2024.

Research Process and Details

1. Analysis of Cytoarchitectural Heterogeneity

The study first analyzed the cytoarchitectural heterogeneity of the DMN using postmortem histological data. Researchers used ultra-high-resolution 3D reconstructed brain slices from the BigBrain database, which were derived from a 65-year-old male and silver-stained to highlight cell bodies. By classifying the cytoarchitecture of the DMN regions, the researchers found that the DMN contains various cell types, ranging from areas specialized in unimodal sensory processing to those involved in multimodal and memory-related processing. Specifically, the DMN includes five cell types, with eulaminate-i (heteromodal cortex) being significantly overrepresented compared to other functional networks.

2. Structural Connectivity Analysis

Next, the research team combined diffusion-weighted imaging (DWI) technology to analyze the structural connectivity of the DMN. They used a navigation efficiency (ENAV) model to evaluate the communication efficiency between the DMN and other brain regions. The results showed that certain regions within the DMN (such as the anterior cingulate and precuneus) had higher communication efficiency with other brain regions, especially those related to sensory processing. This indicates that there is a core region within the DMN that receives external input, while other regions are relatively insulated from environmental input.

3. Functional Signal Flow Analysis

To further understand the functional signal flow within the DMN, the research team used regression dynamic causal modeling (RDCM) to analyze resting-state functional magnetic resonance imaging (fMRI) data. They found that the output signals of the DMN maintain a unique balance across different levels of the sensory hierarchy. Unlike other functional networks, the output signal strength of the DMN is evenly distributed across different cortical types, indicating that the DMN can influence all levels of sensory processing in a relatively consistent manner.

4. Individual-Level Validation

To verify the universality of the findings, the research team conducted high-resolution quantitative T1 relaxometry MRI experiments on eight healthy individuals. The results showed that the microstructural axis at the individual level had a high degree of similarity with the cytoarchitectural axis in the postmortem histological data, further supporting the conclusion that the DMN contains a “receptive zone” that receives external input and a “core zone” that is relatively insulated.

Research Results

1. Cytoarchitectural Heterogeneity of the DMN: The DMN contains various cell types, with eulaminate-i (heteromodal cortex) being significantly overexpressed, suggesting that the DMN has a unique role in integrating multimodal information.
2. Structural Connectivity of the DMN: Certain regions within the DMN exhibit higher communication efficiency with other brain regions, especially those related to sensory processing, while other regions are relatively insulated from external input.
3. Functional Signal Flow of the DMN: The output signals of the DMN maintain a unique balance across different levels of the sensory hierarchy, indicating that the DMN can influence all levels of sensory processing in a relatively consistent manner.
4. Individual-Level Validation: The microstructural axis at the individual level showed a high degree of similarity with the cytoarchitectural axis in the histological data, further validating the universality of the findings.

Conclusions and Implications

This study systematically reveals for the first time the complex relationships between the cytoarchitecture, neural connectivity, and functional signal flow of the DMN. By combining postmortem histology with various in vivo neuroimaging techniques, the researchers discovered that the DMN exhibits significant cytoarchitectural heterogeneity and contains a “receptive zone” that receives external input and a “core zone” that is relatively insulated. Additionally, the DMN shows unique balance in its signal output, enabling it to influence all levels of sensory processing in a relatively consistent manner. These findings provide an important anatomical foundation for understanding the broad role of the DMN in human cognition and behavior.

Research Highlights

1. Multimodal Technique Integration: The study combines postmortem histology with various in vivo neuroimaging techniques, providing a comprehensive understanding of the DMN’s structure.
2. Unique Signal Output Balance: The DMN exhibits unique balance in its signal output, offering new insights into its role across the sensory hierarchy.
3. Individual-Level Validation: The study validated the universality of the results at the individual level through high-resolution quantitative T1 relaxometry imaging, enhancing the reliability of the research.

Other Valuable Information

The study also points out that the complex cytoarchitecture and connectivity of the DMN may explain its wide involvement in various cognitive states. For example, certain regions within the DMN may play different roles in different tasks, while the entire network can coordinate activities across different brain regions through balanced signal output. This finding provides new directions for future research, particularly regarding the dynamic reconfiguration of the DMN during cognitive tasks and its potential role in neurological disorders.