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Deficits in cognitive abilities are commonly observed among individuals with multiple sclerosis (MS). Recent neuroimaging studies have provided evidence for the existence of cortical plasticity in MS, with cognitively impaired participants recruiting additional brain areas to perform challenging tasks. The existence of altered cerebral activations in MS provides hope for the utilization of neural resources to reduce cognitive deficits that challenge everyday living in MS by employing alternative interventions such as cognitive and fitness training. In this study, we examined whether higher physical fitness levels enhance cognitive and neural plasticity in MS patients. The present study is the first to investigate the impact of cardiorespiratory fitness on cerebrovascular functioning of MS patients. 24 participants with relapsing-remitting MS were recruited for the study. All participants went through a fitness assessment and were scanned in a 3 T MRI system during the Paced Visual Serial Addition Test (PVSAT). Higher fitness levels were associated with faster behavioral performance and greater recruitment of right IFG/MFG, a region of the cerebral cortex recruited by MS patients during performance of PVSAT to purportedly compensate for the cognitive deterioration attributable to MS. In contrast, lower levels of fitness were associated with enhanced ACC activity, suggestive of the presence of greater interference and the potential for error in lower fit MS participants. These results are promising, suggesting the need for further investigation of the utility of aerobic fitness training as a possible method to support the development of additional cortical resources in an attempt to counter the cognitive decline resulting from MS.

Although training-induced changes in brain activity have been previously examined, plasticity associated with executive functions remains understudied. In this study, we examined training-related changes in cortical activity during a dual task requiring executive control. Two functional magnetic resonance imaging (fMRI) sessions, one before training and one after training, were performed on both a control group and a training group. Using a region-of-interest analysis, we examined Time x Group and Time x Group x Condition interactions to isolate training-dependent changes in activation. We found that most regions involved in dual-task processing before training showed reductions in activation after training. Many of the decreases in activation were correlated with improved performance on the task. We also found an area in the dorsolateral prefrontal cortex that showed an increase in activation for the training group for the dual-task condition, which was also correlated with improved performance. These results are discussed in relation to the efficacy of training protocols for modulating attention and executive functions, dual-task processing, and fMRI correlates of plasticity.

Background: The present study examined whether aerobic fitness training of older humans can increase brain volume in regions associated with age-related decline in both brain structure and cognition., Methods: Fifty-nine healthy but sedentary community-dwelling volunteers, aged 60-79 years, participated in the 6-month randomized clinical trial. Half of the older adults served in the aerobic training group, the other half of the older adults participated in the toning and stretching control group. Twenty young adults served as controls for the magnetic resonance imaging (MRI), and did not participate in the exercise intervention. High spatial resolution estimates of gray and white matter volume, derived from 3D spoiled gradient recalled acquisition MRI images, were collected before and after the 6-month fitness intervention. Estimates of maximal oxygen uptake (VO2) were also obtained., Results: Significant increases in brain volume, in both gray and white matter regions, were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning (nonaerobic) control group. As predicted, no significant changes in either gray or white matter volume were detected for our younger participants., Conclusions: These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans. Furthermore, these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults.

We provide a brief review of the literature on exercise effects on brain and cognition. To this end, we focus on both prospective and retrospective human epidemiological studies that have examined the influence of exercise and physical activity on cognition and dementia. We then examine the relatively small set of human randomized clinical trials that have, for the most part, focused on exercise training effects on cognition. Next, we discuss animal research that has examined the molecular, cellular, and behavioral effects of exercise training. Finally, we conclude with a summary and brief discussion of important future directions of research on fitness cognition and brain.

In this manuscript we provide a brief review of the recent literature that has examined the relationship among fitness training, cognition and brain. We began with a discussion of the non-human animal literature that has examined the relationship among these factors. Next we discuss recent epidemiological studies of the relationship between physical activity and fitness and cognition and age-related disease such as Alzheimer's dementia. We then discuss the results of randomized clinical trials of fitness training on human cognition. Finally, we conclude with a review of the nascent literature that has begun to employ neuroimaging techniques to examine fitness training effects on human brain. In general, the results are promising and suggest that fitness may serve a neuroprotective function for aging humans.

Previous dual-task neuroimaging studies have not discriminated between brain regions involved in preparing to make more than one response from those involved in the management and execution of two tasks. To isolate the effects of dual-task processing while minimizing effects related to task-preparatory processes, we employed a blocked event-related design in which single trials and dual trials were randomly and unpredictably intermixed for one block (mixed block) and presented in isolation of one another during other blocks (pure blocks). Any differences between dual-task and single-task trials within the mixed block would be related to dual-task performance while minimizing any effects related to preparatory differences between the conditions. For this comparison, we found dual-task-related activation throughout inferior prefrontal, temporal, extrastriate, and parietal cortices and the basal ganglia. In addition, when comparing the single task within the mixed block with the single task presented in the pure block of trials, the regions involved in processes important in the mixed block yet unrelated to dual-task operations could be specified. In this comparison, we report a pattern of activation in right inferior prefrontal and superior parietal cortices. Our results argue that a variety of neural regions remain active during dual-task performance even after minimizing task-preparatory processes, but some regions implicated in dual-task performance in previous studies may have been due to task-preparation processes. Furthermore, our results suggest that dual-task operations activate the same brain areas as the single tasks, but to a greater magnitude than the single tasks. These results are discussed in relation to current conceptions of the neural correlates of dual-task performance.

The authors assessed individual differences in cortical recruitment, brain morphology, and inhibitory task performance. Similar to previous studies, older adults tended toward bilateral activity during task performance more than younger adults. However, better performing older adults showed less bilateral activity than poorer performers, contrary to the idea that additional activity is universally compensatory. A review of the results and of extant literature suggests that compensatory activity in prefrontal cortex may only be effective if the additional cortical processors brought to bear on the task can play a complementary role in task performance. Morphological analyses revealed that frontal white matter tracts differed as a function of performance in older adults, suggesting that hemispheric connectivity might impact both patterns of recruitment and cognitive performance., (Copyright (c) 2005 APA, all rights reserved.)

Determining the benefits and/or drawbacks of hormone replacement therapy (HRT) on women's health is an imperative public health goal. Research in rodents suggests benefits of estrogen on neuronal growth and function. However, little research has investigated the effects of HRT on brain tissue in humans. We used high-resolution magnetic resonance imaging and an optimized voxel-based morphometric technique to examine the effects of HRT on brain volume in postmenopausal women. We report two main results: (a) HRT is associated with the sparing of grey matter in prefrontal, parietal, and temporal brain regions and white matter in medial temporal lobe regions, and (b) longer durations of therapy are associated with greater sparing of grey matter tissue. HRT should be considered a possible mediator of age-related neural decline in both grey and white matter tissues.

It has been well established that moderate physiological or emotional arousal modulates memory. However, there is some controversy about whether the source of arousal must be semantically related to the information to be remembered. To test this idea, 35 healthy young adult participants learned a list of common nouns and afterward viewed a semantically unrelated, neutral or emotionally arousing videotape. The tape was shown after learning to prevent arousal effects on encoding or attention, instead influencing memory consolidation. Heart rate increase was significantly greater in the arousal group, and negative affect was significantly less reported in the non-arousal group after the video. The arousal group remembered significantly more words than the non-arousal group at both 30 min and 24 h delays, despite comparable group memory performance prior to the arousal manipulation. These results demonstrate that emotional arousal, even from an unrelated source, is capable of modulating memory consolidation. Potential reasons for contradictory findings in some previous studies, such as the timing of "delayed" memory tests, are discussed.

We report here the first investigation of the effective connectivity between neural structures supporting attentional control using structural equation modeling and functional magnetic resonance imaging (fMRI). Attentional control was examined by employing a modified version of the flanker task. We found that the inconsistent condition elicited a significantly greater number of path coefficients than the consistent condition. In addition, we report that the strength of the prefrontal paths common to both conditions were not different, but that the remaining six paths were different between conditions. Importantly, these results suggest that the relationship between regions supporting attentional control differ between task conditions but the strength of the relationship between some prefrontal regions is invariant between task conditions. Additionally, we found that the paths were significantly lateralized to the right hemisphere. These results are discussed in relation to theories of the function of each region in attentional control.

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.

We investigated the relationship between behavioral measures of conflict and the degree of activity in the anterior cingulate cortex (ACC). We reanalyzed an existing data set that employed the Stroop task using functional magnetic resonance imaging [Milham et al., Brain Cogn 2002;49:277-296]. Although we found no changes in the behavioral measures of conflict from the first to the second half of task performance, we found a reliable reduction in the activity of the anterior cingulate cortex. This result suggests the lack of a strong relationship between behavioral measurements of conflict and anterior cingulate activity. A concomitant increase in dorsolateral prefrontal cortex activity was also found, which may reflect a tradeoff in the neural substrates involved in supporting conflict resolution, detection, or monitoring processes. A second analysis of the data revealed that the duration of an experiment can dramatically affect interpretations of the results, including the roles in which particular regions are thought to play in cognition. These results are discussed in relation to current conceptions of ACC's role in attentional control. In addition, we discuss the implication of our results with current conceptions of conflict and of its instantiation in the brain. Hum. Brain Mapping 21:96-105, 2004., (Copyright 2003 Wiley-Liss, Inc.)

In the first century, ce, the Roman satirist Juneval famously observed Orandum est, ut sit mens sana in corpore sano, or "A sound mind in a sound body is something to be prayed for." This implicit link between mental and physical health, also paralleled by Eastern philosophies and practices such as tai chi, has survived the millennia since Juneval and his contemporaries. More recently, controlled examinations of the effects of physical fitness on cognitive performance have shown that improving cardiovascular fitness (CVF) can help to reduce the deleterious effects of age on cognition and brain structure. Thus, as we age, it may well be the case that a sound mind is a natural concomitant of a sound body. Numerous cross-sectional and longitudinal studies have examined the effects of aerobic exercise on cognitive performance in aging humans since earlier studies, which found that physically fit older adults performed better on simple cognitive tasks than their less-fit counterparts. This base of knowledge recently has been furthered through examinations of cortical structure (Colcombe et al., 2003) and neurocognitive function in aging humans via functional and structural magnetic resonance imaging techniques. In this manuscript, we will briefly review some of our recent research on the effects of CVF on brain function, structure, and behavior in older adults. We will then outline some of our current and future directions in this area., (Copyright 2004 Humana Press Inc.)

Background: The human brain gradually loses tissue from the third decade of life onward, with concomitant declines in cognitive performance. Given the projected rapid growth in aged populations, and the staggering costs associated with geriatric care, identifying mechanisms that may reduce or reverse cerebral deterioration is rapidly emerging as an important public health goal. Previous research has demonstrated that aerobic fitness training improves cognitive function in older adults and can improve brain health in aging laboratory animals, suggesting that aerobic fitness may provide a mechanism to improve cerebral health in aging humans. We examined the relationship between aerobic fitness and in vivo brain tissue density in an older adult population, using voxel-based morphometric techniques., Methods: We acquired high-resolution magnetic resonance imaging scans from 55 older adults. These images were segmented into gray and white matter maps, registered into stereotaxic space, and examined for systematic variation in tissue density as a function of age, aerobic fitness, and a number of other health markers., Results: Consistent with previous studies of aging and brain volume, we found robust declines in tissue densities as a function of age in the frontal, parietal, and temporal cortices. More importantly, we found that losses in these areas were substantially reduced as a function of cardiovascular fitness, even when we statistically controlled for other moderator variables., Conclusions: These findings extend the scope of beneficial effects of aerobic exercise beyond cardiovascular health, and they suggest a strong solid biological basis for the benefits of exercise on the brain health of older adults.

Several recent studies of aging and cognition have attributed decreases in the efficiency of working memory processes to possible declines in attentional control, the mechanism(s) by which the brain attempts to limit its processing to that of task-relevant information. Here we used fMRI measures of neural activity during performance of the color-word Stroop task to compare the neural substrates of attentional control in younger (ages: 21-27 years old) and older participants (ages: 60-75 years old) during conditions of both increased competition (incongruent and congruent neutral) and increased conflict (incongruent and congruent neutral). We found evidence of age-related decreases in the responsiveness of structures thought to support attentional control (e.g., dorsolateral prefrontal and parietal cortices), suggesting possible impairments in the implementation of attentional control in older participants. Consistent with this notion, older participants exhibited more extensive activation of ventral visual processing regions (i.e., temporal cortex) and anterior inferior prefrontal cortices, reflecting a decreased ability to inhibit the processing of task-irrelevant information. Also, the anterior cingulate cortex, a region involved in evaluatory processes at the level of response (e.g., detecting potential for error), showed age-related increases in its sensitivity to the presence of competing color information. These findings are discussed in terms of newly emerging models of attentional control in the human brain.