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1.  Aerobic fitness is associated with greater efficiency of the network underlying cognitive control in preadolescent children 
Neuroscience  2011;199:166-176.
This study examined whether individual differences in aerobic fitness are associated with differences in activation of cognitive control brain networks in preadolescent children. As expected, children performed worse on a measure of cognitive control compared to a group of young adults. However, individual differences in aerobic fitness were associated with cognitive control performance among children. Lower-fit children had disproportionate performance cost in accuracy with increasing task difficulty, relative to higher-fit children. Brain activation was compared between performance-matched groups of lower- and higher-fit children. Fitness groups differed in brain activity for regions associated with response execution and inhibition, task set maintenance, and top-down regulation. Overall, differing activation patterns coupled with different patterns of brain-behavior correlations suggest an important role of aerobic fitness in modulating task strategy and the efficiency of neural networks that implement cognitive control in preadolescent children.
doi:10.1016/j.neuroscience.2011.10.009
PMCID: PMC3237764  PMID: 22027235
exercise; physical activity; aerobic fitness; executive control; fMRI; development
2.  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.
doi:10.1155/2012/939285
PMCID: PMC3415086  PMID: 22900181
3.  Aerobic Fitness and Response Variability in Preadolescent Children Performing a Cognitive Control Task 
Neuropsychology  2011;25(3):333-341.
OBJECTIVE
To investigate the relationship between aerobic fitness and cognitive variability in preadolescent children.
METHOD
Forty-eight preadolescent children (25 males, 23 females, mean age = 10.1 years) were grouped into higher- and lower-fit groups according to their performance on a test of aerobic capacity (VO2max). Cognitive function was measured via behavioral responses to a modified flanker task. The distribution in reaction time was calculated within each participant to assess intra-individual variability of performance. Specifically, the standard deviation and coefficient variation of reaction time were used to represent cognitive variability.
RESULTS
Preadolescent children, regardless of fitness, exhibited longer reaction time, increased response variability, and decreased response accuracy to incongruent compared to congruent trials. Further, higher-fit children were less variable in their response time and more accurate in their responses across conditions of the flanker task, while no group differences were observed for response speed.
CONCLUSION
These findings suggest that fitness is associated with better cognitive performance during a task that varies cognitive control demands, and extends this area of research to suggest that intra-individual variability may be a useful measure to examine the relationship between fitness and cognition during preadolescence.
doi:10.1037/a0022167
PMCID: PMC3086950  PMID: 21443340
Physical Activity; Executive Control; Standard Deviation; Coefficient of Variation; Reaction Time
4.  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.
doi:10.1002/brb3.30
PMCID: PMC3343297  PMID: 22574272
Aging; brain; exercise; fitness; human; N-acetylaspartate; working memory
5.  Aerobic Fitness is Associated With Hippocampal Volume in Elderly Humans 
Hippocampus  2009;19(10):1030-1039.
Deterioration of the hippocampus occurs in elderly individuals with and without dementia, yet individual variation exists in the degree and rate of hippocampal decay. Determining the factors that influence individual variation in the magnitude and rate of hippocampal decay may help promote lifestyle changes that prevent such deterioration from taking place. Aerobic fitness and exercise are effective at preventing cortical decay and cognitive impairment in older adults and epidemiological studies suggest that physical activity can reduce the risk for developing dementia. However, the relationship between aerobic fitness and hippocampal volume in elderly humans is unknown. In this study, we investigated whether individuals with higher levels of aerobic fitness displayed greater volume of the hippocampus and better spatial memory performance than individuals with lower fitness levels. Furthermore, in exploratory analyses, we assessed whether hippocampal volume mediated the relationship between fitness and spatial memory. Using a region-of-interest analysis on magnetic resonance images in 165 nondemented older adults, we found a triple association such that higher fitness levels were associated with larger left and right hippocampi after controlling for age, sex, and years of education, and larger hippocampi and higher fitness levels were correlated with better spatial memory performance. Furthermore, we demonstrated that hippocampal volume partially mediated the relationship between higher fitness levels and enhanced spatial memory. Our results clearly indicate that higher levels of aerobic fitness are associated with increased hippocampal volume in older humans, which translates to better memory function.
doi:10.1002/hipo.20547
PMCID: PMC3072565  PMID: 19123237
aging; MRI; spatial memory; cognition; brain
6.  BDNF is Associated With Age-Related Decline in Hippocampal Volume 
Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood.
doi:10.1523/JNEUROSCI.6251-09.2010
PMCID: PMC3069644  PMID: 20392958
brain-derived neurotrophic factor; hippocampus; human; brain; caudate nucleus; aging
7.  A cross-sectional study of hormone treatment and hippocampal volume in postmenopausal women: Evidence for a limited window of opportunity 
Neuropsychology  2010;24(1):68-76.
The influence of hormone treatment on brain and cognition in postmenopausal women has been a controversial topic. Contradictory patterns of results have prompted speculation that a critical period, or a limited window of opportunity, exists for hormone treatment to protect against cognitive and neural decline in older women. Consistent with this hypothesis, studies in both humans and rodents indicate that the latency between the time of menopause and the initiation of hormone treatment is an important factor in determining whether hormone treatment will prevent or exacerbate cognitive impairment. In this cross-sectional study of 102 postmenopausal women, we examined whether hippocampal, amygdala, or caudate nucleus volumes and spatial memory performance were related to the interval between menopause and the initiation of hormone treatment. Consistent with a critical period hypothesis, we found that shorter intervals between menopause and the initiation of hormone treatment, as determined by self-report, were associated with larger hippocampal volumes compared with longer intervals between menopause and treatment initiation. Initiation of hormone treatment at the time of menopause was also associated with larger hippocampal volumes when compared to peers who had never used hormone treatment. Furthermore, these effects were independent from potentially confounding factors such as age, years of education, the duration of hormone treatment, current or past use of hormone therapy, the type of therapy, and the age at menopause. Larger hippocampal volumes in women who initiated hormone treatment at the time of menopause failed to translate to improved spatial memory performance. There was no relationship between the timing of hormone initiation, spatial memory performance, and amygdala or caudate nucleus volume. Our results provide support for the idea that there is a limited window of opportunity at the time of menopause for hormone treatment to influence hippocampal volume, yet the degree to which these effects translate to improved memory performance is uncertain.
doi:10.1037/a0017292
PMCID: PMC2843433  PMID: 20063947
8.  Plasticity of Brain Networks in a Randomized Intervention Trial of Exercise Training in Older Adults 
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.
doi:10.3389/fnagi.2010.00032
PMCID: PMC2947936  PMID: 20890449
exercise; aging; functional connectivity; fMRI; default mode network; executive function; aerobic fitness
9.  Cardiorespiratory Fitness and Attentional Control in the Aging Brain 
A growing body of literature provides evidence for the prophylactic influence of cardiorespiratory fitness on cognitive decline in older adults. This study examined the association between cardiorespiratory fitness and recruitment of the neural circuits involved in an attentional control task in a group of healthy older adults. Employing a version of the Stroop task, we examined whether higher levels of cardiorespiratory fitness were associated with an increase in activation in cortical regions responsible for imposing attentional control along with an up-regulation of activity in sensory brain regions that process task-relevant representations. Higher fitness levels were associated with better behavioral performance and an increase in the recruitment of prefrontal and parietal cortices in the most challenging condition, thus providing evidence that cardiorespiratory fitness is associated with an increase in the recruitment of the anterior processing regions. There was a top-down modulation of extrastriate visual areas that process both task-relevant and task-irrelevant attributes relative to the baseline. However, fitness was not associated with differential activation in the posterior processing regions, suggesting that fitness enhances attentional function by primarily influencing the neural circuitry of anterior cortical regions. This study provides novel evidence of a differential association of fitness with anterior and posterior brain regions, shedding further light onto the neural changes accompanying cardiorespiratory fitness.
doi:10.3389/fnhum.2010.00229
PMCID: PMC3024830  PMID: 21267428
cardiorespiratory fitness; Stroop task; cognitive and attentional control
10.  Trouble Crossing the Bridge: Altered Interhemispheric Communication of Emotional Images in Anxiety 
Emotion (Washington, D.C.)  2008;8(5):684-692.
Worry is thought to involve a strategy of cognitive avoidance, in which internal verbalization acts to suppress threatening emotional imagery. We tested the hypothesis that worry-prone individuals would exhibit patterns of between-hemisphere communication that reflect cognitive avoidance. Specifically, we predicted slower transfer of threatening images from the left to the right hemisphere among worriers. ERP measures of interhemispheric transfer time supported this prediction. Left-to-right hemisphere transfer times for angry faces were relatively slower for individuals scoring high in self-reported worry compared to those scoring low, while transfer of happy and neutral faces did not differ between groups. These results suggest that altered interhemispheric communication may constitute one mechanism of cognitive avoidance in worry.
doi:10.1037/a0012910
PMCID: PMC2575130  PMID: 18837618
anxiety; avoidance; interhemispheric communication; corpus callosum
11.  Anxiety and Error Monitoring: Increased Error Sensitivity or Altered Expectations? 
Brain and cognition  2007;64(3):247-256.
This study tested the prediction that the error-related negativity (ERN), a physiological measure of error monitoring, would be enhanced in anxious individuals, particularly in conditions with threatening cues. Participants made gender judgments about faces whose expressions were either happy, angry, or neutral. Replicating prior studies, midline scalp negativities were greater following errors than following correct responses. In addition, state anxiety interacted with facial expression to predict ERN amplitudes. Counter to predictions, participants high in state anxiety displayed smaller ERNs for angry-face blocks and larger ERNs for happy-face blocks, compared to less anxious participants. These results are inconsistent with the simple notion that anxiety enhances error-sensitivity globally. Rather, we interpret the findings within an expectancy violation framework, in which anxious participants have altered expectations for success and failure in the context of happy and angry facial cues, with greater ERN amplitudes when expectations are violated.
doi:10.1016/j.bandc.2007.03.006
PMCID: PMC1995669  PMID: 17482740

Results 1-11 (11)