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1.  A review of cardiorespiratory fitness-related neuroplasticity in the aging brain 
The literature examining the relationship between cardiorespiratory fitness and the brain in older adults has increased rapidly, with 30 of 34 studies published since 2008. Here we review cross-sectional and exercise intervention studies in older adults examining the relationship between cardiorespiratory fitness and brain structure and function, typically assessed using Magnetic Resonance Imaging (MRI). Studies of patients with Alzheimer's disease are discussed when available. The structural MRI studies revealed a consistent positive relationship between cardiorespiratory fitness and brain volume in cortical regions including anterior cingulate, lateral prefrontal, and lateral parietal cortex. Support for a positive relationship between cardiorespiratory fitness and medial temporal lobe volume was less consistent, although evident when a region-of-interest approach was implemented. In fMRI studies, cardiorespiratory fitness in older adults was associated with activation in similar regions as those identified in the structural studies, including anterior cingulate, lateral prefrontal, and lateral parietal cortex, despite heterogeneity among the functional tasks implemented. This comprehensive review highlights the overlap in brain regions showing a positive relationship with cardiorespiratory fitness in both structural and functional imaging modalities. The findings suggest that aerobic exercise and cardiorespiratory fitness contribute to healthy brain aging, although additional studies in Alzheimer's disease are needed.
PMCID: PMC3709413  PMID: 23874299
exercise; physical fitness; physical activity; fMRI; structural MRI; diffusion tensor imaging; episodic memory; executive functions
2.  Cardiorespiratory Fitness and Motor Skills in Relation to Cognition and Academic Performance in Children – A Review 
Journal of Human Kinetics  2013;36:55-68.
Different elements of physical fitness in children have shown a declining trend during the past few decades. Cardiorespiratory fitness and motor skills have been associated with cognition, but the magnitude of this association remains unknown. The purpose of this review is to provide an overview of the relationship of cardiorespiratory fitness and motor skills with cognitive functions and academic performance in children up to 13 years of age. Cross-sectional studies suggest that children with higher cardiorespiratory fitness have more efficient cognitive processing at the neuroelectric level, as well as larger hippocampal and basal ganglia volumes, compared to children with lower cardiorespiratory fitness. Higher cardiorespiratory fitness has been associated with better inhibitory control in tasks requiring rigorous attention allocation. Better motor skills have been related to more efficient cognitive functions including inhibitory control and working memory. Higher cardiorespiratory fitness and better motor skills have also been associated with better academic performance. Furthermore, none of the studies on cardiorespiratory fitness have revealed independent associations with cognitive functions by controlling for motor skills. Studies concerning the relationship between motor skills and cognitive functions also did not consider cardiorespiratory fitness in the analyses. The results of this review suggest that high levels of cardiorespiratory fitness and motor skills may be beneficial for cognitive development and academic performance but the evidence relies mainly on cross-sectional studies.
PMCID: PMC3661895  PMID: 23717355
physical fitness; movement skills; physical activity; children; scholastic achievement
3.  An fMRI Investigation of Working Memory and its Relationship with Cardiorespiratory Fitness in Pediatric Posterior Fossa Tumor Survivors who received Cranial Radiation Therapy 
Pediatric blood & cancer  2012;60(4):669-675.
The present study investigated the relationship between cardiorespiratory fitness and executive functioning in pediatric brain tumor survivors who received cranial radiation. This population is known to show executive dysfunction and lower rates of aerobic exercise compared to peers.
Nine adolescent survivors of pediatric posterior fossa tumor completed an n-back working memory task during a functional MRI scan, as well as cardiorespiratory fitness testing on a cycle ergometer.
Neuroimaging findings indicated typical activation patterns associated with working memory, mainly in the frontal-parietal network. Higher cardiorespiratory fitness was related to better performance on a behavioral measure of working memory and more efficient neural functioning.
This study provides preliminary evidence that cardiorespiratory fitness may be related to executive functioning, particularly working memory, in pediatric brain tumor survivors. Descriptions of the brain regions recruited for working memory by pediatric brain tumor survivors may be used to inform future interventions or indicators of treatment efficacy.
PMCID: PMC3541446  PMID: 23042746
Brain Neoplasms; Neuropsychology; Executive Function; Physical Fitness; Magnetic Resonance Imaging
4.  Improved cerebral oxygenation response and executive performance as a function of cardiorespiratory fitness in older women: a fNIRS study 
Cardiorespiratory fitness has been shown to protect and enhance cognitive and brain functions, but little is known about the cortical mechanisms that underlie these changes in older adults. In this study, functional near infrared spectroscopy (fNIRS) was used to investigate variations in oxyhemoglobin [HbO2] and in deoxyhemoglobin [HHb] in the dorsolateral prefrontal cortex (DLPFC) during the performance of an executive control task in older women with different levels of cardiorespiratory fitness (VO2max). Thirty-four women aged 60–77 years were classified as high-fit and low-fit based on VO2max measures. They all performed a control counting (CNT) task and the Random Number Generation (RNG) task at two different paces (1 number/1 s and 1 number/1.5 s), allowing to manipulate task difficulty, while hemodynamic responses in the bilateral DLPFCs were recorded using continuous-wave NIRS. The behavioral data revealed that the high-fit women showed significantly better performance on the RNG tasks compared with the low-fit women. The high-fit women showed significant increases in [HbO2] responses in both left and right DLPFCs during the RNG task, while the low-fit women showed significantly less activation in the right DLPFC compared with the right DLPFC of the high-fit women and compared with their own left DLPFC. At the level of the whole sample, increases in the [HbO2] responses in the right DLPFC were found to mediate in part the relationship between VO2max level and executive performance during the RNG task at 1.5 s but not at 1 s. These results provide support for the cardiorespiratory fitness hypothesis and suggest that higher levels of aerobic fitness in older women are related to increased cerebral oxygen supply to the DLPFC, sustaining better cognitive performance.
PMCID: PMC4189417  PMID: 25339900
prefrontal cortex; functional near-infrared spectroscopy (fNIRS); executive functions; aerobic fitness; aging
5.  Cardiorespiratory fitness and preserved medial temporal lobe volume in Alzheimer's Disease 
Exercise and cardiorespiratory (CR) fitness may moderate age-related regional brain changes in nondemented older adults (ND). The relationship of fitness to Alzheimer's disease (AD) related brain change is understudied, particularly in the hippocampus which is disproportionately affected in early AD. The role of apolipoprotein E4 (apoE4) genotype in modulating this relationship is also unknown. Nondemented (n=56) and early-stage AD subjects (n=61) over age 65 had MRI and CR fitness assessments. Voxel-based morphometry (VBM) techniques were utilized to identify AD-related atrophy. We analyzed the relationship of CR fitness with white and gray matter within groups, assessed fitness-related brain volume change in areas most affected by AD-related atrophy, and then analyzed differential fitness-brain relationships between apoE4 carriers. Atrophy was present in the medial temporal, temporal, and parietal cortices in subjects with mild AD. There was a significant positive correlation of CR fitness with parietal and medial temporal volume in AD subjects. ND subjects did not have a significant relationship between brain volume and CR fitness in the global or SVC analyses. There was not a significant interaction for fitness × apoE4 genotype in either group. In early-stage AD, cardiorespiratory fitness is associated with regional brain volumes in the medial temporal and parietal cortices suggesting that maintaining cardiorespiratory fitness may modify AD-related brain atrophy.
PMCID: PMC2760037  PMID: 19812458
Alzheimer Disease; Cardiorespiratory Fitness; Physical Activity; Hippocampus; Voxel-Based-Morphometry; APOE; Dementia; Aging
6.  The association between aerobic fitness and executive function is mediated by prefrontal cortex volume 
Brain, Behavior, and Immunity  2011;26(5):811-819.
Aging is marked by a decline in cognitive function, which is often preceded by losses in gray matter volume. Fortunately, higher cardiorespiratory fitness (CRF) levels are associated with an attenuation of age-related losses in gray matter volume and a reduced risk for cognitive impairment. Despite these links, we have only a rudimentary understanding of whether fitness-related increases in gray matter volume lead to elevated cognitive function. In this cross-sectional study, we examined whether the association between higher aerobic fitness levels and elevated executive function was mediated by greater gray matter volume in the prefrontal cortex (PFC). One hundred and forty-two older adults (mean age = 66.6 years) completed structural magnetic resonance imaging (MRI) scans, CRF assessments, and performed Stroop and spatial working memory (SPWM) tasks. Gray matter volume was assessed using an optimized voxel-based morphometry approach. Consistent with our predictions, higher fitness levels were associated with (a) better performance on both the Stroop and SPWM tasks, and (b) greater gray matter volume in several regions, including the dorsolateral PFC (DLPFC). Volume of the right inferior frontal gyrus and precentral gyrus mediated the relationship between CRF and Stroop interference while a non-overlapping set of regions bilaterally in the DLPFC mediated the association between CRF and SPWM accuracy. These results suggest that specific regions of the DLPFC differentially relate to inhibition and spatial working memory. Thus, fitness may influence cognitive function by reducing brain atrophy in targeted areas in healthy older adults.
PMCID: PMC3321393  PMID: 22172477
cardiorespiratory fitness; executive function; voxel-based morphometry; cortical volume; prefrontal cortex; mediation
7.  Caudate Nucleus Volume Mediates the Link between Cardiorespiratory Fitness and Cognitive Flexibility in Older Adults 
Journal of Aging Research  2012;2012:939285.
The basal ganglia play a central role in regulating the response selection abilities that are critical for mental flexibility. In neocortical areas, higher cardiorespiratory fitness levels are associated with increased gray matter volume, and these volumetric differences mediate enhanced cognitive performance in a variety of tasks. Here we examine whether cardiorespiratory fitness correlates with the volume of the subcortical nuclei that make up the basal ganglia and whether this relationship predicts cognitive flexibility in older adults. Structural MRI was used to determine the volume of the basal ganglia nuclei in a group of older, neurologically healthy individuals (mean age 66 years, N = 179). Measures of cardiorespiratory fitness (VO2max), cognitive flexibility (task switching), and attentional control (flanker task) were also collected. Higher fitness levels were correlated with higher accuracy rates in the Task Switching paradigm. In addition, the volume of the caudate nucleus, putamen, and globus pallidus positively correlated with Task Switching accuracy. Nested regression modeling revealed that caudate nucleus volume was a significant mediator of the relationship between cardiorespiratory fitness, and task switching performance. These findings indicate that higher cardiorespiratory fitness predicts better cognitive flexibility in older adults through greater grey matter volume in the dorsal striatum.
PMCID: PMC3415086  PMID: 22900181
8.  Cardiorespiratory Fitness and Brain Atrophy in Early Alzheimer’s Disease 
Neurology  2008;71(3):210-216.
Examine the correlation of cardiorespiratory fitness with brain atrophy and cognition in early-stage Alzheimer’s disease (AD).
In normal aging physical fitness appears to mitigate functional and structural age-related brain changes. Whether this is observed in AD is not known.
Nondemented (n=64) and early-stage AD subjects (n=57) had MRI and standard clinical and psychometric evaluations. Peak oxygen consumption (VO2peak), the standard measure of cardiorespiratory fitness, was assessed during a graded treadmill test. Normalized whole brain volume, a brain atrophy estimate, was determined by MRI. Pearson’s correlation and linear regression were used to assess fitness in relation to brain volume and cognitive performance.
Cardiorespiratory fitness (VO2peak) was modestly reduced in AD (34.7(5.0)ml/kg/min) vs. nondemented subjects (38.1(6.3)ml/kg/min, p=0.002). In early AD, VO2peak was associated with whole brain volume (beta=0.35, p=0.02) and white matter volume (beta=0.35, p=0.04) after controlling for age. Controlling for additional covariates of sex, dementia severity, physical activity, and physical frailty did not attenuate the relationships. VO2peak was associated with performance on delayed memory and digit symbol in early AD but not after controlling for age. In nondemented participants, there was no relationship between fitness and brain atrophy. Fitness in nondemented participants was associated with better global cognitive performance (r=0.30, p=0.02) and performance on Trailmaking A and B, Stroop, and delayed logical memory but not after controlling for age.
Increased cardiorespiratory fitness is associated with reduced brain atrophy in AD. Cardiorespiratory fitness may moderate AD-related brain atrophy or a common underlying AD-related process may impact both brain atrophy and cardiorespiratory fitness.
PMCID: PMC2657657  PMID: 18625967
Alzheimer’s disease; cardiorespiratory fitness; atrophy
9.  Individual differences in emotion-cognition interactions: emotional valence interacts with serotonin transporter genotype to influence brain systems involved in emotional reactivity and cognitive control 
The serotonin transporter gene (5-HTTLPR) influences emotional reactivity and attentional bias toward or away from emotional stimuli, and has been implicated in psychopathological states, such as depression and anxiety disorder. The short allele is associated with increased reactivity and attention toward negatively-valenced emotional information, whereas the long allele is associated with increased reactivity and attention toward positively-valenced emotional information. The neural basis for individual differences in the ability to exert cognitive control over these bottom-up biases in emotional reactivity and attention is unknown, an issue investigated in the present study. Healthy adult participants were divided into two groups, either homozygous carriers of the 5-HTTLPR long allele or homozygous carriers of the short allele, and underwent functional magnetic resonance imaging (fMRI) while completing an Emotional Stroop-like task that varied in the congruency of task-relevant and task-irrelevant information and the emotional valence of the task-irrelevant information. Behaviorally, participants demonstrated the classic “Stroop effect” (responses were slower for incongruent than congruent trials), which did not differ by 5-HTTLPR genotype. However, fMRI results revealed that genotype influenced the degree to which neural systems were engaged depending on the valence of the conflicting task-irrelevant information. While the “Long” group recruited prefrontal control regions and superior temporal sulcus during conflict when the task-irrelevant information was positively-valenced, the “Short” group recruited these regions during conflict when the task-irrelevant information was negatively-valenced. Thus, participants successfully engaged cognitive control to overcome conflict in an emotional context using similar neural circuitry, but the engagement of this circuitry depended on emotional valence and 5-HTTLPR status. These results suggest that the interplay between emotion and cognition is modulated, in part, by a genetic polymorphism that influences serotonin neurotransmission.
PMCID: PMC3701233  PMID: 23847500
5-HTTLPR; Stroop; fMRI; prefrontal cortex (PFC); eye-gaze; anxiety; positive affect
10.  Beyond vascularization: aerobic fitness is associated with N-acetylaspartate and working memory 
Brain and Behavior  2012;2(1):32-41.
Aerobic exercise is a promising form of prevention for cognitive decline; however, little is known about the molecular mechanisms by which exercise and fitness impacts the human brain. Several studies have postulated that increased regional brain volume and function are associated with aerobic fitness because of increased vascularization rather than increased neural tissue per se. We tested this position by examining the relationship between cardiorespiratory fitness and N-acetylaspartate (NAA) levels in the right frontal cortex using magnetic resonance spectroscopy. NAA is a nervous system specific metabolite found predominantly in cell bodies of neurons. We reasoned that if aerobic fitness was predominantly influencing the vasculature of the brain, then NAA levels should not vary as a function of aerobic fitness. However, if aerobic fitness influences the number or viability of neurons, then higher aerobic fitness levels might be associated with greater concentrations of NAA. We examined NAA levels, aerobic fitness, and cognitive performance in 137 older adults without cognitive impairment. Consistent with the latter hypothesis, we found that higher aerobic fitness levels offset an age-related decline in NAA. Furthermore, NAA mediated an association between fitness and backward digit span performance, suggesting that neuronal viability as measured by NAA is important in understanding fitness-related cognitive enhancement. Since NAA is found exclusively in neural tissue, our results indicate that the effect of fitness on the human brain extends beyond vascularization; aerobic fitness is associated with neuronal viability in the frontal cortex of older adults.
PMCID: PMC3343297  PMID: 22574272
Aging; brain; exercise; fitness; human; N-acetylaspartate; working memory
11.  Aerobic Exercise Improves Cognition for Older Adults with Glucose Intolerance, A Risk Factor for Alzheimer’s Disease 
Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57–83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-β (Aβ40 and Aβ42). Six months of aerobic exercise improved executive function (MANCOVA, p = 0.04), cardiorespiratory fitness (MANOVA, p = 0.03), and insulin sensitivity (p = 0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p = 0.01). For Aβ42, plasma levels tended to decrease for the aerobic group relative to controls (p = 0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline.
PMCID: PMC3049111  PMID: 20847403
Aerobic exercise; Alzheimer’s disease; cognition; dementia; diabetes; executive function; glucose intolerance; prediabetes
12.  Aerobic Fitness is Associated with Gray Matter Volume and White Matter Integrity in Multiple Sclerosis 
Brain research  2009;1341C:41-51.
Alterations in gray and white matter have been well documented in individuals with multiple sclerosis. Severity and extent of such brain tissue damage have been associated with cognitive impairment, disease duration and neurological disability, making quantitative indices of tissue damage important markers of disease progression. In this study, we investigated the association between cardiorespiratory fitness and measures of gray matter atrophy and white matter integrity. Employing a voxel-based approach to analyses of gray matter and white matter, we specifically examined whether higher levels of fitness in multiple sclerosis participants were associated with preserved gray matter volume and integrity of white matter. We found a positive association between cardiorespiratory fitness and regional gray matter volumes and higher focal fractional anisotropy values. Statistical mapping revealed that higher levels of fitness were associated with greater gray matter volume in the midline cortical structures including the medial frontal gyrus, anterior cingulate cortex and the precuneus. Further, we also found increasing levels of fitness were associated with higher fractional anisotropy in the left thalamic radiation and right anterior corona radiata. Both preserved gray matter volume and white-matter tract integrity were associated with better performance on measures of processing speed. Taken together, these results suggest that fitness exerts a prophylactic influence on the cerebral atrophy observed early on preserving neuronal integrity in multiple sclerosis, thereby reducing long-term disability.
PMCID: PMC2884046  PMID: 19560443
Cortical atrophy; normal appearing gray matter; normal appearing white matter; cardiorespiratory fitness; processing speed; relapsing-remitting multiple sclerosis; neuroplasticity
13.  Physical Activity, Body Mass Index, and Cardiorespiratory Fitness among School Children in Taiwan: A Cross-Sectional Study 
There is evidence that cardiorespiratory fitness and physical activity significantly reduce cardiovascular risks in adults. A better understanding of the association between cardiorespiratory fitness, physical activity, and childhood obesity is vital in assessing the benefits of interventions to prevent obesity. This study was to examine the relationship between physical activity, body mass index, and cardiorespiratory fitness levels in Taiwanese children. A cross-sectional study was designed. Study participants consisted of 2419 school children (1230 males and 1189 females) aged 12 years old living in a southern Taiwan county with one the highest countrywide rates of childhood obesity. The weight status of the participants was defined as underweight, normal, overweight, or obese according to specific criteria. Cardiorespiratory fitness was then assessed by an 800-m run. Participants were queried on their physical activity habits via a questionnaire survey. The overall prevalence of overweight/obesity was 29.6%. Normal, underweight and overweight boys and girls had an increased odds ratio of being categorized with higher cardiorespiratory fitness than obese one for both gender. A significantly higher level of cardiorespiratory fitness was found in children who engaged in regular physical activity than in children who engaged only in irregular physical activity. Obese children are more likely to lack cardiorespiratory fitness. Physically active children have significantly better cardiorespiratory fitness levels than inactive children. This study supports the conclusion that BMI and physical activity are significantly correlated with cardiorespiratory fitness levels. Findings may provide educational professionals with information to assist their developing effective health promotion programs to healthy weight and improving cardiorespiratory fitness for children.
PMCID: PMC4113875  PMID: 25032742
children; obesity; cardiorespiratory; health promotion; school nursing
14.  Effects of Aerobic Exercise on Mild Cognitive Impairment 
Archives of neurology  2010;67(1):71-79.
To examine the effects of aerobic exercise on cognition and other biomarkers associated with Alzheimer disease pathology for older adults with mild cognitive impairment, and assess the role of sex as a predictor of response.
Six-month, randomized, controlled, clinical trial.
Veterans Affairs Puget Sound Health Care System clinical research unit.
Thirty-three adults (17 women) with amnestic mild cognitive impairment ranging in age from 55 to 85 years (mean age,70 years).
Participants were randomized either to a high-intensity aerobic exercise or stretching control group. The aerobic group exercised under the supervision of a fitness trainer at 75% to 85% of heart rate reserve for 45 to 60 min/d, 4 d/wk for 6 months. The control group carried out supervised stretching activities according to the same schedule but maintained their heart rate at or below 50% of their heart rate reserve. Before and after the study, glucometabolic and treadmill tests were performed and fat distribution was assessed using dual-energy x-ray absorptiometry. At baseline, month 3, and month 6, blood was collected for assay and cognitive tests were administered.
Main Outcome Measures
Performance measures on Symbol-Digit Modalities, Verbal Fluency, Stroop, Trails B, Task Switching, Story Recall, and List Learning. Fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulinlike growth factor-I, and β-amyloids 40 and 42.
Six months of high-intensity aerobic exercise had sex-specific effects on cognition, glucose metabolism, and hypothalamic-pituitary-adrenal axis and trophic activity despite comparable gains in cardiorespiratory fitness and body fat reduction. For women, aerobic exercise improved performance on multiple tests of executive function, increased glucose disposal during the metabolic clamp, and reduced fasting plasma levels of insulin, cortisol, and brain-derived neurotrophic factor. For men, aerobic exercise increased plasma levels of insulinlike growth factor I and had a favorable effect only on Trails B performance.
This study provides support, using rigorous controlled methodology, for a potent nonpharma-cologic intervention that improves executive control processes for older women at high risk of cognitive decline. Moreover, our results suggest that a sex bias in cognitive response may relate to sex-based differences in glucometabolic and hypothalamic-pituitary-adrenal axis responses to aerobic exercise.
PMCID: PMC3056436  PMID: 20065132
15.  Exercise, Fitness, and Neurocognitive Function in Older Adults: The “Selective Improvement” and “Cardiovascular Fitness” Hypotheses 
Although basic research has uncovered biological mechanisms by which exercise could maintain and enhance adult brain health, experimental human studies with older adults have produced equivocal results.
This randomized clinical trial aimed to investigate the hypotheses that (a) the effects of exercise training on the performance of neurocognitive tasks in older adults is selective, influencing mainly tasks with a substantial executive control component and (b) performance in neurocognitive tasks is related to cardiorespiratory fitness.
Fifty-seven older adults (65−79 years) participated in aerobic or strength-and-flexibility exercise training for 10 months. Neurocognitive tasks were selected to reflect a range from little (e.g., simple reaction time) to substantial (i.e., Stroop Word–Color conflict) executive control.
Performance in tasks requiring little executive control was unaffected by participating in aerobic exercise. Improvements in Stroop Word–Color task performance were found only for the aerobic exercise group. Changes in aerobic fitness were unrelated to changes in neurocognitive function.
Aerobic exercise in older adults can have a beneficial effect on the performance of speeded tasks that rely heavily on executive control. Improvements in aerobic fitness do not appear to be a prerequisite for this beneficial effect.
PMCID: PMC2748860  PMID: 18825471
Stroop; Wisconsin Card Sort Test; Cardiorespiratory fitness; Executive processing; Aerobic exercise
16.  Cardiorespiratory Fitness Is Associated with Hard and Light Intensity Physical Activity but Not Time Spent Sedentary in 10–14 Year Old Schoolchildren: The HAPPY Study 
PLoS ONE  2013;8(4):e61073.
Sedentary behaviour is a major risk factor for developing chronic diseases and is associated with low cardiorespiratory fitness in adults. It remains unclear how sedentary behaviour and different physical activity subcomponents are related to cardiorespiratory fitness in children. The purpose of this study was to assess how sedentary behaviour and different physical activity subcomponents are associated with 10–14 year-old schoolchildren's cardiorespiratory fitness.
135 schoolchildren (81 girls, 12±1 year) completed 7-day minute-by-minute habitual physical activity monitoring using triaxial accelerometers and undertook a maximal cardiorespiratory fitness test.
After controlling for sex, age, ethnicity, socioeconomic status and total wear time, light physical activity (1.5–2.9 METs) was negatively associated (β = −.24, p<.01) and hard physical activity (≥9 METs) positively associated (β = .45, p<.001) with cardiorespiratory fitness. Vigorous and hard physical activity were associated with cardiorespiratory fitness for boys (F = 5.64, p<.01) whereas light, moderate and hard physical activity were associated with physical fitness for girls (F = 10.23, p<.001). No association was found between sedentary time and cardiorespiratory fitness (r = −.13, p>.05). Sedentary to active transitions revealed little variability between cardiorespiratory fitness tertiles.
Hard physical activity (≥9 METs) holds greater potential for cardiorespiratory fitness compared to physical activity of lower intensities. There was no relationship between sedentary behaviour and cardiorespiratory fitness. These findings suggest that, for children, advice should focus on higher intensity physical activity and not sedentary behaviour as a means to maintain or improve cardiorespiratory fitness. Future research should explore longitudinal relationships between hard physical activity, cardiorespiratory fitness and health parameters.
PMCID: PMC3618292  PMID: 23577192
Neuroscience  2008;157(2):319-328.
To improve behavior, one must detect errors and initiate subsequent corrective adaptations. This action monitoring process has been widely studied, but little is known about how one may improve this aspect of cognition. To examine the relationship between cardiorespiratory fitness and action monitoring, we recorded the error-related negativity (ERN), an event-related brain potential believed to index action monitoring, as well as post-error behavioral indices of action monitoring from healthy young adults (18–25 years) who varied in cardiorespiratory fitness. These measures were collected during the execution of flanker tasks emphasizing response accuracy or speed to better assess the specificity of any potential relationships between fitness and action monitoring. Higher fitness was associated with greater post-error accuracy and ERN amplitude during task conditions emphasizing accuracy, as well as greater modulation of these indices across task instruction conditions. These findings suggest that higher fitness is associated with increased cognitive flexibility, evidenced through greater change in action monitoring indices as a function of task parameters. Thus, fitness may benefit action monitoring by selectively increasing cognitive control under conditions where error detection and performance adjustments are more salient.
PMCID: PMC2657808  PMID: 18845227
Cognitive Control; Action Monitoring; Error-Related Negativity (ERN); Event-Related Brain Potentials (ERPs); Fitness
18.  Double Dissociation Between Action-driven and Perception-driven Conflict Resolution Invoking Anterior versus Posterior Brain Systems 
NeuroImage  2009;48(2):381-390.
The ability to select and integrate relevant information in the presence of competing irrelevant information can be enhanced by advance information to direct attention and guide response selection. Attentional preparation can reduce perceptual and response conflict, yet little is known about the neural source of conflict resolution, whether it is resolved by modulating neural responses for perceptual selection to emphasize task-relevant information or for action selection to inhibit pre-potent responses to interfering information. We manipulated perceptual information that either matched or did not match the relevant color feature of an upcoming Stroop stimulus and recorded hemodynamic brain responses to these events. Longer reaction times to incongruent than congruent color-word Stroop stimuli indicated conflict; however, conflict was even greater when a color cue correctly predicted the Stroop target’s color (match) than when it did not (nonmatch). A predominantly anterior network was activated for Stroop-match and a predominantly posterior network was activated for Stroop-nonmatch. Thus, when a stimulus feature did not match the expected feature, a perceptually-driven posterior attention system was engaged, whereas when interfering, automatically-processed semantic information required inhibition of pre-potent responses, an action-driven anterior control system was engaged. These findings show a double dissociation of anterior and posterior cortical systems engaging in different types of control for perceptually-driven and action-driven conflict resolution.
PMCID: PMC2753237  PMID: 19573610
Attention; Conflict; Control; fMRI; Perceptual Cueing
19.  Basal Ganglia Volume Is Associated with Aerobic Fitness in Preadolescent Children 
Developmental Neuroscience  2010;32(3):249-256.
The present investigation is the first to explore the association between childhood aerobic fitness and basal ganglia structure and function. Rodent research has revealed that exercise influences the striatum by increasing dopamine signaling and angiogenesis. In children, higher aerobic fitness levels are associated with greater hippocampal volumes, superior performance on tasks of attentional and interference control, and elevated event-related brain potential indices of executive function. The present study used magnetic resonance imaging to investigate if higher-fit and lower-fit 9- and 10-year-old children exhibited differential volumes of other subcortical brain regions, specifically the basal ganglia involved in attentional control. The relationship between aerobic fitness, dorsal and ventral striatum volumes and performance on an attention and inhibition Eriksen flanker task was also examined. The results indicated that higher-fit children showed superior flanker task performance compared to lower-fit children. Higher-fit children also showed greater volumes of the dorsal striatum, and dorsal striatum volume was negatively associated with behavioral interference. The results support the claim that the dorsal striatum is involved in cognitive control and response resolution and that these cognitive processes vary as a function of aerobic fitness. No relationship was found between aerobic fitness, the volume of the ventral striatum and flanker performance. The findings suggest that increased childhood aerobic fitness is associated with greater dorsal striatal volumes and that this is related to enhanced cognitive control. Because children are becoming increasingly overweight, unhealthy and unfit, understanding the neurocognitive benefits of an active lifestyle during childhood has important public health and educational implications.
PMCID: PMC3696376  PMID: 20693803
Brain; Development; Exercise; MRI; Physical activity; Neurocognition; Neuroimaging; Striatum
20.  The influence of cardiorespiratory fitness on strategic, behavioral, and electrophysiological indices of arithmetic cognition in preadolescent children 
The current study investigated the influence of cardiorespiratory fitness on arithmetic cognition in forty 9–10 year old children. Measures included a standardized mathematics achievement test to assess conceptual and computational knowledge, self-reported strategy selection, and an experimental arithmetic verification task (including small and large addition problems), which afforded the measurement of event-related brain potentials (ERPs). No differences in math achievement were observed as a function of fitness level, but all children performed better on math concepts relative to math computation. Higher fit children reported using retrieval more often to solve large arithmetic problems, relative to lower fit children. During the arithmetic verification task, higher fit children exhibited superior performance for large problems, as evidenced by greater d' scores, while all children exhibited decreased accuracy and longer reaction time for large relative to small problems, and incorrect relative to correct solutions. On the electrophysiological level, modulations of early (P1, N170) and late ERP components (P3, N400) were observed as a function of problem size and solution correctness. Higher fit children exhibited selective modulations for N170, P3, and N400 amplitude relative to lower fit children, suggesting that fitness influences symbolic encoding, attentional resource allocation and semantic processing during arithmetic tasks. The current study contributes to the fitness-cognition literature by demonstrating that the benefits of cardiorespiratory fitness extend to arithmetic cognition, which has important implications for the educational environment and the context of learning.
PMCID: PMC4017138  PMID: 24829556
addition; pediatric-cognition; strategy; ERPs; mathematics
21.  Reduced dorsal anterior cingulate cortical activity during emotional regulation and top-down attentional control in Generalized Social Phobia (GSP), Generalized Anxiety Disorder (GAD) and comorbid GSP/GAD 
Biological psychiatry  2012;72(6):476-482.
Generalized Social Phobia (GSP) and Generalized Anxiety Disorder (GAD) are both associated with emotion dysregulation. In healthy subjects, research implicates dorsal anterior cingulate (dACC) in both explicit emotion regulation and top-down attentional control. While studies have examined these processes in GSP or GAD, no work compares findings across the two disorders. Moreover, no work examines functioning in cases comorbid for both disorders (GSP/GAD). Here we compare the neural correlates of explicit emotion regulation (EER) and top-down attentional control (TAC) in GSP, GAD, and GSP/GAD.
Medication-free adults with GSP (EER n=19; TAC n=18), GAD (EER n=17; TAC n =17), GSP/GAD (EER n=17; TAC=15), or no psychopathology (EER n=18; TAC n=18). During EER, individuals alternatively viewed, up-regulated, and down-regulated responses to emotional pictures. During TAC, they performed an emotional Stroop task.
For both tasks, significant group-by-condition interactions emerged in dACC and parietal cortices. Healthy adults showed significantly increased recruitment during emotion regulation, relative to emotion-picture viewing. GAD, GSP, and GSP/GAD subjects showed no such increases, with all three groups differing from healthy adults but not from each other. Evidence of emotion-related disorder-specificity emerged in medial prefrontal cortex (MPFC) and amygdala. This disorder-specific responding varied as a function of stimulus emotion content but not emotion-regulatory demands.
GSP and GAD both involve reduced capacity for engaging emotion-regulation brain networks, whether explicitly or via top-down attentional control. A reduced ability to recruit regions implicated in top-down attention might represent a general risk factor for anxiety disorders.
PMCID: PMC3424322  PMID: 22592057
imaging; social anxiety; generalized anxiety; emotion regulation; anterior cingulate cortex; top-down attentional control
22.  Age, physical fitness, and attention 
Psychophysiology  2009;46(2):379-387.
The influence of age and fitness on the neuroelectric correlates of attentional orienting and processing during stimulus discrimination were investigated. Younger and older adult participants completed a maximal aerobic exercise test and were separated into higher- and lower-fit groups according to their cardiorespiratory fitness. Task performance and event-related potential measures were obtained during two- and three-stimulus oddball tasks. Results indicated that fitness may ameliorate or protect against cognitive aging for simple stimulus discriminations. Increases in task difficulty indicated that fitness may not be sufficient to overcome age-related deficits in stimulus discrimination. Further, fitness did not influence attentional orienting. The findings suggest that fitness-related changes in cognitive function may originate from other attentional mechanisms. Theoretical implications are discussed.
PMCID: PMC2763440  PMID: 19170947
Age; Fitness; Stimulus discrimination; Attentional orienting; Task difficulty; P300; P3a; P3b
23.  Cardiorespiratory Fitness Levels and its Correlates Among Adults with Diabetes 
The purpose of this study is to report cardiorespiratory fitness levels among adults with diabetes and report differences by demographic (eg, body mass index) and behavioral (eg, physical activity) variables.
Data from the 1999-2004 National Health and Nutrition Examination Survey (NHANES) were used in the analyses. Cardiorespiratory fitness was assessed using a non-exercise prediction equation and through a submaximal treadmill-based test using heart rate extrapolation. Participants completed a questionnaire to assess various demographic and behavior variables. Seventy eight participants met inclusion criteria and constituted the analyzed sample.
The majority (55.1%) of participants were estimated as having low or moderate cardiorespiratory fitness. Results showed that for both methods normal weight individuals had greater cardiorespiratory fitness than obese individuals, and for the non-exercise prediction equation, participants who sat during the day and did not walk very much had lower cardiorespiratory fitness (mean = 26.1 mL/kg/min [95% CI: 18.9-33.4]) than those doing heavy work or carrying heavy loads (mean = 34.6 mL/kg/min [95% CI: 30.2-39.1]).
These results suggest that obese and inactive adults with diabetes may be at an increased risk for morbidities and mortality associated with low cardiorespiratory fitness. Physical therapists are encouraged to apply evidence-based principles for exercise prescription and physical activity counseling to help patients with diabetes regulate their blood glucose control and improve cardiorespiratory fitness.
PMCID: PMC3691706  PMID: 23801902
obesity; physical activity; physical therapy
24.  Variations of response time in a selective attention task are linked to variations of functional connectivity in the attentional network 
NeuroImage  2010;54(1):541-549.
Although variations of response time (RT) within a particular experimental condition are typically ignored, they may sometimes reflect meaningful changes in the efficiency of cognitive and neural processes. In the present study, we investigated whether trial-by-trial variations of response time (RT) in a cross-modal selective attention task were associated with variations of functional connectivity between brain regions that are thought to underlie attention. Sixteen healthy young adults performed an audiovisual selective attention task, which involved attending to a relevant visual letter while ignoring an irrelevant auditory letter, as we recorded their brain activity using functional magnetic resonance imaging (fMRI). In line with predictions, variations of RT were associated with variations of functional connectivity between the anterior cingulate cortex and various other brain regions that are posited to underlie attentional control, such as the right dorsolateral prefrontal cortex and bilateral regions of the posterior parietal cortex. They were also linked to variations of functional connectivity between anatomically early and anatomically late regions of the relevant-modality visual cortex whose communication is thought to be modulated by attentional control processes. By revealing that variations of RT in a selective attention task are linked to variations of functional connectivity in the attentional network, the present findings suggest that variations of attention may contribute to trial-by-trial fluctuations of behavioral performance.
PMCID: PMC2962675  PMID: 20728549
attention; visual; auditory; functional connectivity; fMRI; response time
25.  Regional Brain Differences in the Effect of Distraction During the Delay Interval of a Working Memory Task 
Brain research  2007;1152:171-181.
Working memory (WM) comprises operations whose coordinated action contributes to our ability to maintain focus on goal-relevant information in the presence of distraction. The present study investigated the nature of distraction upon the neural correlates of WM maintenance operations by presenting task-irrelevant distracters during the interval between the memoranda and probes of a delayed-response WM task. The study used a region of interest (ROIs) approach to investigate the role of anterior (e.g., lateral and medial prefrontal cortex - PFC) and posterior (e.g., parietal and fusiform cortices) brain regions that have been previously associated with WM operations. Behavioral results showed that distracters that were confusable with the memorandum impaired WM performance, compared to either the presence of non-confusable distracters or to the absence of distracters. These different levels of distraction led to differences in the regional patterns of delay interval activity measured with event-related functional magnetic resonance imaging (fMRI). In the anterior ROIs, dorsolateral PFC activation was associated with WM encoding and maintenance, and in maintaining a preparatory state, and ventrolateral PFC activation was associated with the inhibition of distraction. In the posterior ROIs, activation of the posterior parietal and fusiform cortices was associated with WM and perceptual processing, respectively. These findings provide novel evidence concerning the neural systems mediating the cognitive and behavioral responses during distraction, and places frontal cortex at the top of the hierarchy of the neural systems responsible for cognitive control.
PMCID: PMC3514456  PMID: 17459348
Declarative Memory; Interference; Functional Neuroimaging

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