The goal is to investigate brain systems that mediate cognitive, affective, and rewardprocessing in humans and to determine how these systems are influenced by late life depression, bygenetic risk factors associated with depression, and by experimental manipulations of serotoninlevels. Behavioral challenge tasks will be use during functional magnetic resonance imaging (fMRI) toinvestigate four specific aims: (1) We will complete studies initiated in the current funding period thatinvestigate the influence of vascular lesions upon the interaction of ventral systems for emotionalregulation and dorsal systems for executive control in patients with late life depression. Theseon-going studies also include an assessment of current clinical status, and whether treatment hasled to a remission from depression. (2) We will characterize genetic influences upon the neuralprocessing of emotional and rewarding stimuli using a task developed in current period thatmeasures activity in amygdala, ventromedial and orbital frontal cortex, and ventral frontal cortex, and asecond task that measures activity in striatal, midbrain, and dorsal systems associated withdecisions about rewards. (3) We will evaluate the effects of neurotransmitter levels upon the neuralprocessing of emotional and rewarding stimuli. Neuroimaging and neurophysiological studiesreveal correlations between measures of neuronal activity and measures of behavioral states (e.g.,mood, decision preference, response time). Such correlations suggest functional relationships, buttypically remain untested. To functionally probe the effects of emotional/reward systems uponexecutive processing systems, we will pharmacologically manipulate levels of the neurotransmitterserotonin using ATD. Observation of systematic shifts in mood, behavioral preferences, or sensitivityto reward outcomes would have profound implications for understanding phenotypic variation inbehavior associated with conditions such as depression, addiction, and anxiety syndromes. (4) Wewill evaluate the effects of mood changes upon the neural processing of emotional and rewardingstimuli. A common consequence of depression is anhedonia, or the inability to derive pleasure (orother emotional reaction) from normally rewarding stimuli. We will use procedures developed in thecurrent period to manipulate mood state over short time intervals, and we will investigate howtransient negative mood influences activation in brain systems that process emotional and rewardingstimuli.
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