title: Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades.
abstract: The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20-29 to 70-79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging.
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center San Antonio San Antonio, TX, USA.
authors.forename: Karl
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Physics, Florida International University Miami, FL, USA.
authors.forename: Angela R
authors.initials: AR
authors.lastname: Laird
authors.affiliation: Department of Mathematics and College of Education, Texas State University San Marcos, TX, USA.
authors.forename: Larry R
authors.initials: LR
authors.lastname: Price
authors.affiliation: Department of Psychiatry, Yale University School of MedicineNew Haven, CT, USA; Olin Neuropsychiatry Research Center, Institute of Living, Hartford HospitalHartford, CT, USA.
authors.forename: D Reese
authors.initials: DR
authors.lastname: McKay
authors.affiliation: Genomics Computing Center, South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine Edinburg, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: Department of Psychiatry, Yale University School of MedicineNew Haven, CT, USA; Olin Neuropsychiatry Research Center, Institute of Living, Hartford HospitalHartford, CT, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
authors.affiliation: Research Imaging Institute, University of Texas Health Science Center San AntonioSan Antonio, TX, USA; Research Service, South Texas Veterans Health Care SystemSan Antonio, TX, USA; Neuroimaging Laboratory, Shenzhen University School of MedicineShenzhen, Guangdong, China.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Fox
keywords: default mode network (DMN); functional connectivity (FC); meta-analytic connectivity modeling; normal aging; structural equation modeling (SEM)