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Considerable progress has been made
in elucidating the neural pathways underlying conditioned
fear in experimental animals. This work has implicated
circuits centered around the amygdala, and interactions between
the amygdala, hippocampus and medial frontal cortex (mPFC),
in the acquisition and/or expression of different aspects
of conditioned fear. New research in humans has confirmed
essential aspects of the work in animals. These facts
strongly suggest that studies of fear in animals can reveal
important insights into the mechanisms of fear in humans,
possibly including humans with pathological fear, such as
occurs in anxiety disorders and paranoid psychosis. Further,
given that threatening stimuli, which are prominent in the
lives of patients with fear disorders, trigger stress reactions,
that stress is believed to exacerbate symptoms in psychiatric
patients, including those with pathological fear, and that
the same brain regions implicated in normal fear are also
strongly implicated in the regulation of stress hormones,
we propose that stress-induced alterations in fear circuits
may contribute to the development or maintenance of pathologic
fear.
The goals of this center, therefore, are to explore the relation
between fear and stress in experimental animals and to examine
whether the effects of stress on fear circuits mimics changes
that occur in fear-related disorders in humans. To do
this, we will use the same behavioral paradigm, fear conditioning,
to study rats, normal humans, and patients with fear disorders.
The overall aim of the animal work is to examine the effects
of stress on the behavioral functions, physiology, and morphology
of fear circuits. The overall aim of the studies of
normal humans is to use fMRI to both extend our understanding
of fear mechanisms in the human brain and to develop new probes
for testing patients with fear disorders. And the overall
aim of the studies of patients with fear disorders is to determine
whether the normal patterns of functional brain activation
during fear are altered, and whether these alterations are
consistent with the effects of stress on fear circuits, as
determined in the animal work. |
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