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The functional brain favours segregated modular connectivity at old age unless affected by neurodegeneration

Lookup NU author(s): Dr Joe Necus, Dr Ramtin Mehraram, Professor John O'Brien, Professor Andrew BlamireORCiD, Professor Marcus Kaiser, Professor John-Paul TaylorORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2021, The Author(s).Brain’s modular connectivity gives this organ resilience and adaptability. The ageing process alters the organised modularity of the brain and these changes are further accentuated by neurodegeneration, leading to disorganisation. To understand this further, we analysed modular variability—heterogeneity of modules—and modular dissociation—detachment from segregated connectivity—in two ageing cohorts and a mixed cohort of neurodegenerative diseases. Our results revealed that the brain follows a universal pattern of high modular variability in metacognitive brain regions: the association cortices. The brain in ageing moves towards a segregated modular structure despite presenting with increased modular heterogeneity—modules in older adults are not only segregated, but their shape and size are more variable than in young adults. In the presence of neurodegeneration, the brain maintains its segregated connectivity globally but not locally, and this is particularly visible in dementia with Lewy bodies and Parkinson’s disease dementia; overall, the modular brain shows patterns of differentiated pathology.

Publication metadata

Author(s): Chen X, Necus J, Peraza LR, Mehraram R, Wang Y, O'Brien JT, Blamire A, Kaiser M, Taylor J-P

Publication type: Article

Publication status: Published

Journal: Communications Biology

Year: 2021

Volume: 4

Issue: 1

Online publication date: 16/08/2021

Acceptance date: 22/07/2021

Date deposited: 06/11/2023

ISSN (electronic): 2399-3642

Publisher: Nature Research


DOI: 10.1038/s42003-021-02497-0


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Funder referenceFunder name
Alzheimer’s Research UK in partnership with Hidden Hearing ARUK-PPG2016A-2
China Scholarship Council 201706450045
China Scholarship Council 201306455001
Guangci Professorship Program of Ruijin Hospital (Shanghai Jiao Tong University)
Fundamental Research Funds for the Central Universities 16CX06050A
MR/T004347/1Medical Research Council (MRC)
Wellcome Trust Fellowship WT088441MA
the National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) at Newcastle University
the National Natural Science Foundation of P.R. China 62072468
the National Natural Science Foundation of Shandong Province ZR2018MF017