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      Plasticity of Brain Networks in a Randomized Intervention Trial of Exercise Training in Older Adults

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          Abstract

          Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (0.008 <  f < 0.08 Hz) coherence of cognitively relevant and sensory brain networks in older adults who participated in a 1-year intervention trial, comparing the effects of aerobic and non-aerobic fitness training on brain function and cognition. Results showed that aerobic training improved the aging brain's resting functional efficiency in higher-level cognitive networks. One year of walking increased functional connectivity between aspects of the frontal, posterior, and temporal cortices within the Default Mode Network and a Frontal Executive Network, two brain networks central to brain dysfunction in aging. Length of training was also an important factor. Effects in favor of the walking group were observed only after 12 months of training, compared to non-significant trends after 6 months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after 6 months and in a Frontal Parietal Network after 12 months, possibly reflecting experience-dependent plasticity. Finally, we found that changes in functional connectivity were behaviorally relevant. Increased functional connectivity was associated with greater improvement in executive function. Therefore the study provides the first evidence for exercise-induced functional plasticity in large-scale brain systems in the aging brain, using functional connectivity techniques, and offers new insight into the role of aerobic fitness in attenuating age-related brain dysfunction.

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          Cardiovascular fitness, cortical plasticity, and aging.

          Cardiovascular fitness is thought to offset declines in cognitive performance, but little is known about the cortical mechanisms that underlie these changes in humans. Research using animal models shows that aerobic training increases cortical capillary supplies, the number of synaptic connections, and the development of new neurons. The end result is a brain that is more efficient, plastic, and adaptive, which translates into better performance in aging animals. Here, in two separate experiments, we demonstrate for the first time to our knowledge, in humans that increases in cardiovascular fitness results in increased functioning of key aspects of the attentional network of the brain during a cognitively challenging task. Specifically, highly fit (Study 1) or aerobically trained (Study 2) persons show greater task-related activity in regions of the prefrontal and parietal cortices that are involved in spatial selection and inhibitory functioning, when compared with low-fit (Study 1) or nonaerobic control (Study 2) participants. Additionally, in both studies there exist groupwise differences in activation of the anterior cingulate cortex, which is thought to monitor for conflict in the attentional system, and signal the need for adaptation in the attentional network. These data suggest that increased cardiovascular fitness can affect improvements in the plasticity of the aging human brain, and may serve to reduce both biological and cognitive senescence in humans.
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            Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI.

            Subtle changes in a subject's breathing rate or depth, which occur naturally during rest at low frequencies (<0.1 Hz), have been shown to be significantly correlated with fMRI signal changes throughout gray matter and near large vessels. The goal of this study was to investigate the impact of these low-frequency respiration variations on both task activation fMRI studies and resting-state functional connectivity analysis. Unlike MR signal changes correlated with the breathing motion ( approximately 0.3 Hz), BOLD signal changes correlated with across-breath variations in respiratory volume ( approximately 0.03 Hz) appear localized to blood vessels and regions with high blood volume, such as gray matter, similar to changes seen in response to a breath-hold challenge. In addition, the respiration-variation-induced signal changes were found to coincide with many of the areas identified as part of the 'default mode' network, a set of brain regions hypothesized to be more active at rest. Regions could therefore be classified as being part of a resting network based on their similar respiration-induced changes rather than their synchronized neuronal activity. Monitoring and removing these respiration variations led to a significant improvement in the identification of task-related activation and deactivation and only slight differences in regions correlated with the posterior cingulate at rest. Regressing out global signal changes or cueing the subject to breathe at a constant rate and depth resulted in an improved spatial overlap between deactivations and resting-state correlations among areas that showed deactivation.
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              Competition between functional brain networks mediates behavioral variability.

              Increased intraindividual variability (IIV) is a hallmark of disorders of attention. Recent work has linked these disorders to abnormalities in a "default mode" network, comprising brain regions routinely deactivated during goal-directed cognitive tasks. Findings from a study of the neural basis of attentional lapses suggest that a competitive relationship between the "task-negative" default mode network and regions of a "task-positive" attentional network is a potential locus of dysfunction in individuals with increased IIV. Resting state studies have shown that this competitive relationship is intrinsically represented in the brain, in the form of a negative correlation or antiphase relationship between spontaneous activity occurring in the two networks. We quantified the negative correlation between these two networks in 26 subjects, during active (Eriksen flanker task) and resting state scans. We hypothesized that the strength of the negative correlation is an index of the degree of regulation of activity in the default mode and task-positive networks and would be positively related to consistent behavioral performance. We found that the strength of the correlation between the two networks varies across individuals. These individual differences appear to be behaviorally relevant, as interindividual variation in the strength of the correlation was significantly related to individual differences in response time variability: the stronger the negative correlation (i.e., the closer to 180 degrees antiphase), the less variable the behavioral performance. This relationship was moderately consistent across resting and task conditions, suggesting that the measure indexes moderately stable individual differences in the integrity of functional brain networks. We discuss the implications of these findings for our understanding of the behavioral significance of spontaneous brain activity, in both healthy and clinical populations.
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                Author and article information

                Journal
                Front Aging Neurosci
                Front. Ag. Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Research Foundation
                1663-4365
                14 May 2010
                26 August 2010
                2010
                : 2
                : 32
                Affiliations
                [1] 1simpleDepartment of Psychology, Beckman Institute, University of Illinois at Urbana-Champaign IL, USA
                [2] 2simpleDepartment of Psychology, The Ohio State University OH, USA
                [3] 3simpleDepartment of Psychology, University of Pittsburgh PA, USA
                [4] 4simpleDepartment of Kinesiology and Community Health, University of Illinois at Urbana-Champaign IL, USA
                Author notes

                Edited by: Lars Nyberg, Umeå University, Sweden

                Reviewed by: Martin Lövdén, Karolinska Institutet, Sweden; Jonas Persson, Stockholms universitet, Sweden

                *Correspondence: Michelle W. Voss, Department of Psychology, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N. Mathews Ave., Urbana, IL 61801, USA. e-mail: mvoss@ 123456illinois.edu
                Article
                10.3389/fnagi.2010.00032
                2947936
                20890449
                ad640080-fc8d-4664-b586-1c79fc1e163e
                Copyright © 2010 Voss, Prakash, Erickson, Basak, Chaddock, Kim, Alves, Heo, Szabo, White, Wójcicki, Mailey, Gothe, Olson, McAuley and Kramer.

                This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

                History
                : 21 April 2010
                : 02 July 2010
                Page count
                Figures: 4, Tables: 6, Equations: 0, References: 102, Pages: 17, Words: 15623
                Categories
                Neuroscience
                Original Research

                Neurosciences
                aerobic fitness,exercise,functional connectivity,executive function,aging,fmri,default mode network

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