FEAR AND THE ANXIETY DISORDERS: BRAIN AND BEHAVIOR

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DESCRIPTION (Applicant's Abstract): The plan of experiments emphasizes basic research on emotion as a framework for comparative clinical studies of phobic and anxious patients. The guiding theory of emotion is derived from animal research on functional brain activity in states of appetitive and defensive motivation. Work by Davis, LeDoux, Fanselow and others has defined a subcortical fear circuit, including the sensory thalamus, amygdala, and periaqueductal central gray. The startle reflex, and autonomic reactivity, are augmented in fearful animals, and this effect depends on an intact fear circuit (e.g., lesions of the amygdala eliminate potentiation). Research conducted on this project has demonstrated a parallel startle potentiation and autonomic change in human beings in fear conditioning, fear imagery, and while attending to unpleasant pictures and auditory stimulation. Exaggerated startle reactions also characterized specific anxiety diagnoses, and may vary with generality of psychopathology. The new basic research examines conical and subcortical reactivity (including brain sites of the animal model) in humans, using both scalp and subdural electrophysiological recording and functional magnetic resonance imaging to determine if fearful and aversive stimuli occasion hypothesized regional patterns of brain activity. Standardized picture stimuli (IAPS) and text evoked imagery, shown to reliably produce emotion related ANS and reflex responses, are presented to subjects in the magnet to determine if there are regional blood oxygen level differences between neutral, pleasant, and aversive stimuli, and how these effects are modulated by arousal. A parallel set of experiments will utilize the EEG to examine cortical responses (ERP and slow-wave) to these same stimuli. Subsequent EEG and fMRI studies will examine phobic subjects (volunteers selected from the normal population) while they view pictures of and/or mentally image, phobic and non-phobic objects. The new clinical research effort includes major anxiety patient assessment studies, using mental imagery and picture paradigms, and multi-measure psychophysiological recording. Comparative analyses are made among anxiety disorders. The sample includes simple and social phobia, panic, post-traumatic stress, obsessive- compulsive, and generalized anxiety disorders. It is planned that the new neural imaging techniques will be added to this clinical protocol, as procedures develop in the basic studies. Goals of the project are to sharpen psychophysiological distinctions between fear (as in phobia), a phasic defensive reaction to a specific stimulus, and anxiety (as in GAD), a more persistent tonic defensive set with components of inhibition and depression. and furthermore, to evaluate memorial, cognitive style, and temperament differences among anxiety disorders, to sharpen differential diagnosis and assess the significance of depressive co-morbidity.