Hierarchical modular organization in the brain: segregation, integration and their balance underlying cognitive diversity

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• Prof. Changsong Zhou. Department of Physics, Centre for Nonlinear Studies, Institute of Computational and Theoretical Studies, Life Science Imaging Centre, Hong Kong Baptist University.
• Thursday 05 March 2026, 12:00-15:00
• Online. .

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The brain is a highly nonlinear complex network system supporting diverse cognitive abilities. The locally segregated and globally integrated processing are the two basic foundations to cognition. However, how does the brain organizes the effective processing of neural information in the local and global scales, so as to support diverse cognitive tasks is not well understood. A physical hypothesis is that the brain system is in a dynamic critical state at rest and can support the balance of separation and integration in supporting diverse cognitive abilities. However, there has been no clear evidence on whether the resting brain is in the segregation-integration balance at the whole-brain scale, and how it is associated to diverse cognitive abilities.

We address the above open interdisciplinary question using an eigenmode-based approach to identify hierarchical modules in structural and functional brain networks by combining large-scale model and fMRI data. The structural brain network displays hierarchal modular organization inherently supporting multilevel segregation and integration modes. We found that the critical state can best recruit such hierarchal modes to maximize the diversity in the functional connectivity. In a large sample of healthy young adults (n=991) from the Human Connectome Project (HCP), we demonstrate that resting brain functional networks are on average close to a balanced state. This state allows for a balanced time dwelling at segregated and integrated configurations, and highly flexible switching between them. Meanwhile, we demonstrate that network segregation, integration and their balance in resting brains predict individual differences in diverse cognitive phenotypes. We also show that weak links, which are largely ignored in network neuroscience, play crucial role in supporting the segregation-integration balance and cognitive functions. Our findings provide a systems level understanding of the brain’s functioning principles in supporting diverse functional demands and cognitive abilities, and advance modern network neuroscience theories of human cognition, which may shed light on dysfunctional segregation and integration in neurodegenerative diseases and neuropsychiatric disorders. Examples of application of the framework to stress and ADHD are briefly presented.

References:

[1] R. Wang, P. Lin, M.X. Liu, Y. Wu, T. Zhou and C.S. Zhou. Hierarchical Connectome Modes and Critical State Jointly Maximize Human Brain Functional Diversity. Phys. Rev. Lett. 123, 038301 (2019).

[2] R. Wang+, M.X. Liu+, X. Cheng, Y. Wu, A. Hildebrandt, and C.S. Zhou. Segregation, integration and balance of large-scale resting brain networks configure different cognitive abilities. Proc Natl Acad Sci USA , 118 (23), e2022288118 (2021).

[3] R. Wang, S.S. Zeng, C.S. Zhou and R.J. Yu, Acute stress promotes brain network integration and reduces state transition variability, Proc Natl Acad Sci USA , 119 (24), e2204144119 (2022).

[4] R. Wang, Y.C. Fan, Y. Wu, Y.-F. Zang, C.S. Zhou, Lifespan associations of resting-state brain functional networks with ADHD symptoms, iScience, 25 (7) (2022).

[5] R. Wang, Chang, Z., Liu, X., Kristanto, D., Guy Gartner, É., Liu, X., Liu, M., Wu, Y., Lui, M., & Zhou, C. (2025). Weak but influential: Nonlinear contributions of structural connectivity to human cognitive abilities and brain functions.（ https://arxiv.org/abs/2505.24125)

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