The goal of this set of projects is to use functional magnetic resonance imaging (fMRI) to compare the degree to which brain regions of adolescents and adults are engaged by tasks involving processing of emotionally salient stimuli. Such work has major public impact because it shapes understandings of the boundaries of normal development. In the absence of such understanding, it is impossible to precisely demarcate the boundaries of abnormal development. There is a particular interest in using the most up-to-date techniques in this area, such as functional connectivity and psychophysiologic interaction analysis approaches. Our group continues to make progress in these areas over the past two years. Research in this area is highly important, as considerable work suggests that changes in emotional experience around adolescence relate to changes in the brain. Based on developmental continuities in the relevant psychological processes, we anticipate considerable similarity across age groups in the topography of brain regions engaged by relevant tasks. In fact, work already completed in this protocol supports this possibility. Specifically, emerging findings are documenting such similarities through a series of publications. However, we hypothesize that developmental differences in cortico-limbic circuits of adolescents and adults will be reflected in patterns of fMRI activation. Again, emerging findings are consistently demostrating data that support this hypothesis. Moreover, we are interested in focusing on increasingly narrow age groups, to clarify the precise ages when specific developmental events might occur. We are actively collecting data on such narrow groups. Specifically, we hypothesize in both adults and adolescents that attention, threat perception, and memory tasks involving the processing of emotionally salient stimuli will engage the amygdala, cingulate gyrus, and association cortex of medial/inferior prefrontal cortex and temporal regions. These findings have been confirmed in initial work. Nevertheless, height of task-associated activation is hypothesized to differ between adolescents and adults within these regions. Moreover, prior studies distinguish puberty vs. age-related aspects of cognitive development: some aspects of attention, threat perception, or memory development relate to changes in chronological age whereas other aspects, particularly those involving emotional processes, relate to pubertal status. Therefore, we expect eventually to use emotion-evoking fMRI tasks to test hypotheses on the presence of complementary, distinguishable puberty vs. age-related components of brain development. Unlike many other findings in the current protocol, relatively few pieces of data have emerged to support these hypotheses, either in the current protocol or in work being performed by others outside or inside the NIMH-IRP. Due to the limited fMRI database on neurodevelopmental aspects of emotional processes, one initial goal of the current project had been to compare brain activation patterns in adults and adolescents, irrespective of pubertal status. As noted above, aspects of this goal already are being met. A second initial goal is to generate behavioral data in adults and adolescents designed to inform the implementation of future fMRI tasks. This goal, too, is actively being met, although implentation of new tasks remains an ongoing goal. Studies accomplishing both goals will facilitate eventual studies designed to distinguish puberty vs. age-related aspects of brain development. To meet these initial goals, the current project implemented a series of studies during the first five years in which data have been collected. For our fMRI studies, brain activation profiles were examined to four sets of emotionally evocative stimuli. This included evocative faces, standardized emotion-inducing picture sets, monetary feedback during a decision task, and threat of a mildly aversive air-puff. In total, an initial set of fMRI studies were completed in samples of psychiatrically healthy adults and adolescents. These studies led to multiple publications in various high-impact journals. The publications appearing in 2008 and 2009 have been particularly noteworthy. Moreover, very high citation rates for publications appearing in previous years have continued to increase the impact of the work performed in this protocol. During the past year, these experiments have been replicated in additional cohorts of healthy adolescents and adults. Moreover, refinements of previously used paradigms have been successfully implemented, and these refinements have led to data collection in increasingly large samples. In each of these, hypothesized brain activation patterns emerged. Some of these tasks involve face emotion processing whereas others rely on simulated social interactions. Still other task utilize fear-conditioning approaches. As with other findings emerging from the current project, results from these studies are summarized in multiple publications from our group. In an effort to replicate these associations, we have acquired further data sets in other samples that are larger than the initial data sets. We continue to actively analyze these data. Finally, for our behavioral studies, neuropsychological data were gathered to facilitate the development of new fMRI tasks. These included data on four additional tasks. In these tasks, between 20-60 subjects were studied, including approximately equal numbers of adolescents and adults. Three additional manuscripts using these data have been submitted and are under-review. We are also in the process of analyzing other data and preparing research reports for other tasks.
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