title: Elevated hippocampal resting-state connectivity underlies deficient neurocognitive function in aging.
abstract: The brain is not idle during rest. Functional MRI (fMRI) studies have identified several resting-state networks, including the default mode network (DMN), which contains a set of cortical regions that interact with a hippocampus (HC) subsystem. Age-related alterations in the functional architecture of the DMN and HC may influence memory functions and possibly constitute a sensitive biomarker of forthcoming memory deficits. However, the exact form of DMN-HC alterations in aging and concomitant memory deficits is largely unknown. Here, using both task and resting data from 339 participants (25-80 y old), we have demonstrated age-related decrements in resting-state functional connectivity across most parts of the DMN, except for the HC network for which age-related elevation of connectivity between left and right HC was found along with attenuated HC-cortical connectivity. Elevated HC connectivity at rest, which was partly accounted for by age-related decline in white matter integrity of the fornix, was associated with lower cross-sectional episodic memory performance and declining longitudinal memory performance over 20 y. Additionally, elevated HC connectivity at rest was associated with reduced HC neural recruitment and HC-cortical connectivity during active memory encoding, which suggests that strong HC connectivity restricts the degree to which the HC interacts with other brain regions during active memory processing revealed by task fMRI. Collectively, our findings suggest a model in which age-related disruption in cortico-hippocampal functional connectivity leads to a more functionally isolated HC at rest, which translates into aberrant hippocampal decoupling and deficits during mnemonic processing.
authors.affiliation: Umeå Center for Functional Brain Imaging, S-90187 Umeå, Sweden; Department of Integrative Medical Biology, Physiology Section and Aging Research Center, Karolinska Institutet and Stockholm University, 11330 Stockholm, Sweden alireza.salami@ki.se.
authors.forename: Alireza
authors.initials: A
authors.lastname: Salami
authors.affiliation: Umeå Center for Functional Brain Imaging, S-90187 Umeå, Sweden;
authors.forename: Sara
authors.initials: S
authors.lastname: Pudas
authors.affiliation: Umeå Center for Functional Brain Imaging, S-90187 Umeå, Sweden; Department of Integrative Medical Biology, Physiology Section and Department of Radiation Sciences, Diagnostic Radiology, Umeå University, S-90187 Umeå, Sweden; and.
authors.forename: Lars
authors.initials: L
authors.lastname: Nyberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D001921:Brain / Q000502:physiology; D001931:Brain Mapping / Q000379:methods; D003071:Cognition; D003072:Cognition Disorders / Q000503:physiopathology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008569:Memory Disorders / Q000503:physiopathology*; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology
keywords: DMN; aging; episodic memory; hippocampus; resting state