Age differences in the functional architecture of the human brain

Roni Setton, Laetitia Mwilambwe-Tshilobo, Manesh Girn, Amber W. Lockrow, Giulia Baracchini, Colleen Hughes, Alexander J. Lowe, Benjamin N. Cassidy, Jian Li, Wen Ming Luh, Danilo Bzdok, Richard M. Leahy, Tian Ge, Daniel S. Margulies, Bratislav Misic, Boris C. Bernhardt, W. Dale Stevens, Felipe De Brigard, Prantik Kundu, Gary R. TurnerR. Nathan Spreng

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


The intrinsic functional organization of the brain changes into older adulthood. Age differences are observed at multiple spatial scales, from global reductions in modularity and segregation of distributed brain systems, to network-specific patterns of dedifferentiation. Whether dedifferentiation reflects an inevitable, global shift in brain function with age, circumscribed, experience-dependent changes, or both, is uncertain. We employed a multimethod strategy to interrogate dedifferentiation at multiple spatial scales. Multi-echo (ME) resting-state fMRI was collected in younger (n = 181) and older (n = 120) healthy adults. Cortical parcellation sensitive to individual variation was implemented for precision functional mapping of each participant while preserving group-level parcel and network labels. ME-fMRI processing and gradient mapping identified global and macroscale network differences. Multivariate functional connectivity methods tested for microscale, edge-level differences. Older adults had lower BOLD signal dimensionality, consistent with global network dedifferentiation. Gradients were largely age-invariant. Edge-level analyses revealed discrete, network-specific dedifferentiation patterns in older adults. Visual and somatosensory regions were more integrated within the functional connectome; default and frontoparietal control network regions showed greater connectivity; and the dorsal attention network was more integrated with heteromodal regions. These findings highlight the importance of multiscale, multimethod approaches to characterize the architecture of functional brain aging.

Original languageEnglish
Pages (from-to)114-134
Number of pages21
JournalCerebral Cortex
Issue number1
StatePublished - 1 Jan 2023


  • connectivity
  • gradients
  • multi-echo fMRI
  • network neuroscience
  • parcellation


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