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This chapter explores that clinical anxiety involves changes in brain systems that are involved in the generation and regulation of normal emotion. It focuses on a core circuit for negative affective reactivity identified in animal and human studies of fear conditioning. The executive working memory system is a set of cortical networks that comprise a system for goal-directed, flexible control over attention and memory. The affective appraisal system is a set of paralimbic cortical and subcortical regions involved in emotion generation and regulation, self-related cognition, long-term memory retrieval, and context based modulation of conditioned fear. The number of functional neuroimaging studies of negative emotion in clinical anxiety disorders has grown at a rapid pace, now reaching a point at which a quantitative meta-analytic review is feasible. Compared to depression, relatively few neuroimaging coupled intervention studies have been reported for each anxiety disorder.