MODULATION OF FEAR-POTENTIATED STARTLE IN HUMANS

点击翻译按钮获取中文摘要

This application proposes a 4-year study to examine fear excitation and fear inhibition processes in healthy individuals using conditioning procedures derived from infra-human studies. Research on animal aversive conditioning has emphasized the role of memory on the maintenance and generalization of fear as a basis for the understanding of the maintenance of emotional disorders. The conceptual framework of the proposed studies is based on animal models of conditioned fear, conditioned inhibition, and extinction. These models have indicated that the retention of excitatory fear conditioning is robust and long lasting, but the retention of inhibitory fear conditioning is fragile, and is disrupted by the passage of time and by changes in contextual information. The present proposal will assess the generalizability and limitations of such findings in humans. Theoretically, the extension of the animal findings to humans would suggest that the over-generalization of fear results from the combination of robust fear conditioning mechanisms and weak fear inhibitory processes. The identification of variables that interfere with the effectiveness of fear reduction procedures could potentially guide therapeutic interventions. We propose to carry out four studies. Study l will establish a conditioned inhibition procedure based on an animal model that uses a serial stimulus presentation. Study 2 will examine the retention of conditioned fear and fear inhibition across time and contexts. Study 3 will assess the retention of extinction across time and contexts. Study 4 will examine contextual fear as opposed to fear to specific stimuli. One important aspect of this proposal is the use of multiple measures of conditioning (i.e., shock expectancy measures, startle reflex skin conductance, and heart rate) to examine the nature of the associative processes during conditioning. The startle reflex will also allow the implementation of very similar experiments in humans and infra-humans. The integration of the results of the present proposal with studies of the neurobiology of the excitation and the inhibition of conditioned fear-potentiated startle in animals, currently under way at Yale University, could clarify the neurobiological bases of the mechanisms that impact the intensity and maintenance of fear in humans. The results will also provide the necessary foundation for further pharmacological and clinical studies of conditioned fear and conditioned fear inhibition in humans.