title: Extrinsic and Intrinsic Brain Network Connectivity Maintains Cognition across the Lifespan Despite Accelerated Decay of Regional Brain Activation.
abstract: The maintenance of wellbeing across the lifespan depends on the preservation of cognitive function. We propose that successful cognitive aging is determined by interactions both within and between large-scale functional brain networks. Such connectivity can be estimated from task-free functional magnetic resonance imaging (fMRI), also known as resting-state fMRI (rs-fMRI). However, common correlational methods are confounded by age-related changes in the neurovascular signaling. To estimate network interactions at the neuronal rather than vascular level, we used generative models that specified both the neural interactions and a flexible neurovascular forward model. The networks' parameters were optimized to explain the spectral dynamics of rs-fMRI data in 602 healthy human adults from population-based cohorts who were approximately uniformly distributed between 18 and 88 years (www.cam-can.com). We assessed directed connectivity within and between three key large-scale networks: the salience network, dorsal attention network, and default mode network. We found that age influences connectivity both within and between these networks, over and above the effects on neurovascular coupling. Canonical correlation analysis revealed that the relationship between network connectivity and cognitive function was age-dependent: cognitive performance relied on neural dynamics more strongly in older adults. These effects were driven partly by reduced stability of neural activity within all networks, as expressed by an accelerated decay of neural information. Our findings suggest that the balance of excitatory connectivity between networks, and the stability of intrinsic neural representations within networks, changes with age. The cognitive function of older adults becomes increasingly dependent on these factors.
  
  
  CONCLUSIONS
  Maintaining cognitive function is critical to successful aging. To study the neural basis of cognitive function across the lifespan, we studied a large population-based cohort (n = 602, 18-88 years), separating neural connectivity from vascular components of fMRI signals. Cognitive ability was influenced by the strength of connection within and between functional brain networks, and this positive relationship increased with age. In older adults, there was more rapid decay of intrinsic neuronal activity in multiple regions of the brain networks, which related to cognitive performance. Our data demonstrate increased reliance on network flexibility to maintain cognitive function, in the presence of more rapid decay of neural activity. These insights will facilitate the development of new strategies to maintain cognitive ability.
authors.affiliation: Centre for Speech, Language and the Brain, Department of Psychology, University of Cambridge, Cambridge CB23 6HT, United Kingdom, Cambridge Centre for Ageing and Neuroscience (Cam-CAN), University of Cambridge and MRC Cognition and Brain Sciences Unit, Cambridge CB2 7EF, United Kingdom kat35@cam.ac.uk.
authors.forename: Kamen A
authors.identifier: http://orcid.org/0000-0002-3178-6363
authors.initials: KA
authors.lastname: Tsvetanov
authors.affiliation: Medical Research Council Cognition and Brain Sciences Unit, Cambridge CB2 7EF, United Kingdom, Cambridge Centre for Ageing and Neuroscience (Cam-CAN), University of Cambridge and MRC Cognition and Brain Sciences Unit, Cambridge CB2 7EF, United Kingdom.
authors.forename: Richard N A
authors.initials: RN
authors.lastname: Henson
authors.affiliation: Centre for Speech, Language and the Brain, Department of Psychology, University of Cambridge, Cambridge CB23 6HT, United Kingdom, Cambridge Centre for Ageing and Neuroscience (Cam-CAN), University of Cambridge and MRC Cognition and Brain Sciences Unit, Cambridge CB2 7EF, United Kingdom.
authors.forename: Lorraine K
authors.initials: LK
authors.lastname: Tyler
authors.affiliation: The Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, United Kingdom, Department of Electronic Engineering, NED University of Engineering and Technology, Karachi, Pakistan.
authors.forename: Adeel
authors.initials: A
authors.lastname: Razi
authors.affiliation: Medical Research Council Cognition and Brain Sciences Unit, Cambridge CB2 7EF, United Kingdom, Cambridge Centre for Ageing and Neuroscience (Cam-CAN), University of Cambridge and MRC Cognition and Brain Sciences Unit, Cambridge CB2 7EF, United Kingdom.
authors.forename: Linda
authors.initials: L
authors.lastname: Geerligs
authors.affiliation: Department of Clinical Neurosciences, Cambridge University, Cambridge CB2 0SP, United Kingdom.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Ham
authors.affiliation: Medical Research Council Cognition and Brain Sciences Unit, Cambridge CB2 7EF, United Kingdom, Department of Clinical Neurosciences, Cambridge University, Cambridge CB2 0SP, United Kingdom, Behavioural and Clinical Neuroscience Institute, Cambridge CB23 6HT, United Kingdom, and Cambridge Centre for Ageing and Neuroscience (Cam-CAN), University of Cambridge and MRC Cognition and Brain Sciences Unit, Cambridge CB2 7EF, United Kingdom.
authors.forename: James B
authors.initials: JB
authors.lastname: Rowe
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000502:physiology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D009434:Neural Pathways / Q000098:blood supply / Q000502:physiology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: aging; between-/within-network; cross-spectral dynamic causal modelling; fMRI; resting-state networks; salience network