How brain structure-function decoupling supports individual cognition and its molecular mechanism.

Area of Science:

• Neuroscience
• Cognitive Science
• Genetics

Background:

• Brain function relies on structural networks, with region-specific, hierarchical links across the neocortex.
• The relationship between hierarchical structure-function decoupling, individual cognition, and underlying molecular mechanisms requires further clarification.

Purpose of the Study:

• To quantify structure-function decoupling using the structural-decoupling index (SDI) in a large cohort.
• To assess the correlation between region-specific SDIs and cognitive traits.
• To explore the molecular basis of structure-function decoupling, including genetic factors and neurotransmitter systems.

Main Methods:

• Utilized a large cohort of healthy subjects to calculate the structural-decoupling index (SDI).
• Employed canonical correlation analysis (CCA) to correlate whole-brain, region-specific SDIs with multiple cognitive traits.
• Predicted cognitive scores using SDIs from primary, association, and all brain networks.
• Investigated genetic factors and neurotransmitter receptor/transporter relationships with SDI.

Main Results:

• Structure-function decoupling exhibits a hierarchical organization across the neocortex, from primary to association networks.
• Higher-level hierarchical SDIs demonstrated superior prediction of cognitive performance compared to lower-level decoupling.
• SDIs correlated with gene expression of receptor-related terms and showed spatial overlap with D2, NET, MOR, and mGluR5 receptors/transporters.

Conclusions:

• Hierarchical structure-function decoupling is associated with individual cognitive abilities.
• The findings highlight the role of specific neurotransmitter systems and genetic factors in regulating brain structure-function relationships.
• This research provides a foundation for understanding the molecular mechanisms underlying structure-function decoupling and its impact on cognition.