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1.  A neuroimaging investigation of the association between aerobic fitness, hippocampal volume, and memory performance in preadolescent children 
Brain research  2010;1358:172-183.
Because children are becoming overweight, unhealthy, and unfit, understanding the neurocognitive benefits of an active lifestyle in childhood has important public health and educational implications. Animal research has indicated that aerobic exercise is related to increased cell proliferation and survival in the hippocampus as well as enhanced hippocampal-dependent learning and memory. Recent evidence extends this relationship to elderly humans by suggesting that high aerobic fitness levels in older adults are associated with increased hippocampal volume and superior memory performance. The present study aimed to further extend the link between fitness, hippocampal volume, and memory to a sample of preadolescent children. To this end, magnetic resonance imaging was employed to investigate whether higher- and lower-fit 9- and 10-year-old children showed differences in hippocampal volume and if the differences were related to performance on an item and relational memory task. Relational but not item memory is primarily supported by the hippocampus. Consistent with predictions, higher-fit children showed greater bilateral hippocampal volumes and superior relational memory task performance compared to lower-fit children. Hippocampal volume was also positively associated with performance on the relational but not the item memory task. Furthermore, bilateral hippocampal volume was found to mediate the relationship between fitness level (VO2 max) and relational memory. No relationship between aerobic fitness, nucleus accumbens volume, and memory was reported, which strengthens the hypothesized specific effect of fitness on the hippocampus. The findings are the first to indicate that aerobic fitness may relate to the structure and function of the preadolescent human brain.
PMCID: PMC3953557  PMID: 20735996
Brain; Children; Exercise; Hippocampus; MRI; Physical activity
2.  Neurobiological markers of exercise-related brain plasticity in older adults 
The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age = 66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF.
PMCID: PMC3544982  PMID: 23123199
exercise; aging; functional connectivity; fMRI; default mode network; aerobic fitness; growth factors
3.  Functional connectivity: a source of variance in the association between cardiorespiratory fitness and cognition? 
Neuropsychologia  2010;48(5):1394-1406.
Over the next twenty years the number of Americans diagnosed with dementia is expected to more than double (CDC 2007). It is, therefore, an important public health initiative to understand what factors contribute to the longevity of a healthy mind. Both default mode network (DMN) function and increased aerobic fitness have been associated with better cognitive performance and reduced incidence of Alzheimer’s disease among older adults. Here we examine the association between aerobic fitness, functional connectivity in the DMN, and cognitive performance. Results showed significant age-related deficits in functional connectivity in both local and distributed DMN pathways. However, in a group of healthy elderly adults, almost half of the age-related disconnections showed increased functional connectivity as a function of aerobic fitness level. Finally, we examine the hypothesis that functional connectivity in the DMN is one source of variance in the relationship between aerobic fitness and cognition. Results demonstrate instances of both specific and global DMN connectivity mediating the relationship between fitness and cognition. We provide the first evidence for functional connectivity as a source of variance in the association between aerobic fitness and cognition, and discuss results in the context of neurobiological theories of cognitive aging and disease.
PMCID: PMC3708614  PMID: 20079755
cognitive aging; fMRI; functional connectivity; aerobic exercise; executive function; spatial memory
4.  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.
PMCID: PMC3237764  PMID: 22027235
exercise; physical activity; aerobic fitness; executive control; fMRI; development
5.  Age-related differences in the involvement of the prefrontal cortex in attentional control 
Brain and cognition  2009;71(3):328-335.
We investigated the relative involvement of cortical regions supporting attentional control in older and younger adults during performance on a modified version of the Stroop task. Participants were exposed to two different types of incongruent trials. One of these, an incongruent-ineligible condition, produces conflict at the non-response level, while the second, an incongruent-eligible condition, produces conflict at both non-response and response levels of information processing. Greater attentional control is needed to perform the incongruent-eligible condition compared to other conditions. We examined the cortical recruitment associated with this task in an event-related functional magnetic resonance imaging paradigm in twenty-five older and twenty-five younger adults. Our results indicated that while younger adults demonstrated an increase in the activation of cortical regions responsible for maintaining attentional control in response to increased levels of conflict, such sensitivity and flexibility of the cortical regions to increased attentional control demands was absent in older adults. These results suggest a limitation in older adults’ capabilities for flexibly recruiting the attentional network in response to increasing attentional demands.
PMCID: PMC2783271  PMID: 19699019
attentional control; aging; fMRI; flexibility; Stroop task; interference; inhibition
6.  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.
PMCID: PMC3024830  PMID: 21267428
cardiorespiratory fitness; Stroop task; cognitive and attentional control
7.  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.
PMCID: PMC2947936  PMID: 20890449
exercise; aging; functional connectivity; fMRI; default mode network; executive function; aerobic fitness
8.  Genetic Contributions to Age-Related Decline in Executive Function: A 10-Year Longitudinal Study of COMT and BDNF Polymorphisms 
Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.
PMCID: PMC2572207  PMID: 18958211
BDNF; COMT; aging; task-switching; cognition; executive control; longitudinal

Results 1-8 (8)