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Updated: Feb 22, 2026

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Weak Higher-Order Interactions in Macroscopic Functional Networks of the Resting Brain
Xuhui Huang1,2,3,4, Kaibin Xu1,2,4,5, Congying Chu1,2,4,5
1Brainnetome Center.
Higher-order interactions (HOIs) in brain networks are weak, suggesting pairwise functional connectivity (FC) analysis is valid for macroscopic brain activity. This finding simplifies our understanding of brain organization at this scale.
Area of Science:
- Neuroscience
- Complex Systems Analysis
- Network Science
Background:
- Brain region interactions are typically studied using functional connectivity (FC), which measures pairwise correlations.
- Higher-order interactions (HOIs) beyond pairwise correlations are crucial for complex systems but their role in the brain is unclear.
Purpose of the Study:
- To investigate the existence and impact of HOIs in macroscopic brain functional networks.
- To determine if HOIs influence brain activity and to explore potential underlying mechanisms.
Main Methods:
- Analysis of blood oxygenation-level-dependent (BOLD) signals from six macroscopic brain networks in 100 resting-state human subjects.
- Examination of binarized BOLD signals to quantify HOIs across various network properties.
- Network modeling to explore dynamical mechanisms potentially underlying HOI levels.
Main Results:
- HOIs within and across macroscopic brain networks were found to be consistently weak.
- HOI weakness persisted irrespective of network size, topology, spatial proximity, scale, or global signal regression.
- Network model simulations indicated weak HOIs near a linear fluctuation regime, mirroring empirical findings.
Conclusions:
- Weak HOIs suggest that pairwise interactions dominate macroscopic brain network activity.
- The findings validate the widespread use of pairwise-based FC approaches for analyzing brain networks.
- This study reveals a potentially simple organizational principle in the brain's macroscopic functional systems.
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