The brain circuits that subserve fearful responses in animals are well worked out and will be the subject of intensive research within this proposed Center. It is now possible to study the degree to which the same neural circuits are involved in pathological human fear. We will study five groups of human patients (in addition to the normal subjects studied with identical paradigms in Project 1 by LeDoux and Phelps above): patients with panic disorder (off SSRIs), patients with panic disorder (successfully treated with SSRIs) (or CBT), patients with post traumatic stress disorder, acutely paranoid patients with schizophrenia, and non-paranoid patients with schizophrenia. We will use fMRI and targeted neurocognitive probes to evaluate the hypothesis that specific abnormal patterns of activation in fear circuitry (including ventromedial prefrontal cortex, amygdala and hippocampus) are associated with each of the three fear-related conditions--panic disorder, post traumatic stress disorder and paranoid schizophrenia. These probes will include both fear conditioning and syndrome-specific emotional memory tasks that have been designed and piloted in human subjects in collaboration with (and based upon preclinical and psychological models of) our basic science and cognitive psychology colleagues in the Center. These include LeDoux and Phelps from Project 1 and McEwen from Project 3. The resources and services of the Functional Neuroimaging Core will be used extensively by this project.
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