The decline in cognitive function during normal aging in healthy adults is associated with significant decreases in cortical thickness and white matter integrity, particularly in prefrontal regions. Our preliminary data suggest that regular practice of meditation may be able to mitigate normal age-related cortical thinning n some loci of pre-frontal cortical gray matter. It has also been proposed that the long-term affective changes associated with meditation practice may be due to neuroplastic changes. Based on our preliminary data, we hypothesize that regular practice of meditation results in cortical thickening of regions that are routinely engaged during meditation practice, and that these morphological changes mediate the salubrious effects reported by long-term practitioners. Therefore, our long-term goal is to determine the relationship between neural structure and cognitive functioning in the cortical regions we have previously identified. This proposal is in line with NCCAM's specific interest in elucidating the mechanisms of action that promote the positive effects of mind-body interventions. We will combine measures of brain gray and white matter structure with measures of behavioral performance in order to identify potential neural substrates that underlie some of the reported benefits of regular meditation practice. As the largest between-group differences were seen in older subjects, we will recruit a cohort of 20 middle-aged meditation practitioners and well-matched controls. All participants will undergo a structural and functional MRI scanning session and attend a data collection session in the General Clinical Research Center. A major goal of this pilot study is to obtain sufficient preliminary data to design a future longitudinal study that will directly test our theory. If our hypothesis is shown to be correct, it will provide compelling evidence in support of meditation as a possible preventive practice that can alleviate symptoms of cognitive decline during normal aging. These findings will also provide a framework upon which more comprehensive future studies can be constructed. ? ? ?