Neurobiology of Fear, Anxiety and Extinction: Implications for Psychotherapy

author: Michael Davis, School of Medicine, Emory University
published: Oct. 20, 2010,   recorded: April 2008,   views: 8342
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Few scientists have charted the grim territory of fear and anxiety with the same doggedness and precision as Michael Davis.

Nearly four decades ago, researchers learned that animals, including humans, startle more when fearful. A sudden noise in a dark, creepy alley provokes a greater reaction than in a well-lit room, for instance. That got Davis and his colleagues wondering what neural mechanisms underlie the startle reflex, and how fear plays a part in the response.

In his talk, Davis describes the meticulous experiments he and others have conducted over many years. Starting with the fear potentiated startle test -- where animals are trained to pair a stimulus such as light, or sound, with a shock -- researchers began to track the pathways that mediate the response in the nervous system. Using chemical tracers that could follow electrical activity in the brain, Davis found a group of cells in the central nucleus of the amygdala that are critical for fear conditioning. “It was a nice day in the laboratory,” he says. When he knocked out this part of the amygdala with drugs or a lesion, it selectively decreased fear potentiated startle.

More studies produced maps showing that outputs of the central nucleus affect other areas of the brain involved in the symptoms of fear and anxiety, such as elevated blood pressure, sweating, clammy skin, panting and pupil dilation. Of particular interest to Davis, though, were the connections between the central nucleus and another part of the amygdale long thought to be interrelated, the bed nucleus of stria terminalis (BNST). When drugs inactivated the BNST, the startle response was completely blocked.

Davis began disentangling the mechanisms of these two areas, and found that a specific peptide, corticotrophin releasing hormone (CRH) “produces a constellation of behaviors that look very much like fear and anxiety” -- and acts on receptors only in the BNST. He began to test the idea of two systems acting in parallel in the brain: fear, of relatively short duration, orchestrated by the central nucleus; and anxiety, more diffuse and sustained, originating in the BNST.

Davis proposes that cognitive inputs (perhaps bad experiences and memories) help drive the release of CRH and long-term anxiety, including common debilitating phobias (fear of heights, darkness) and post-traumatic stress disorder. Research has shown that to extinguish such fears, new kinds of ‘inhibitory’ learning must take place. Davis recently discovered a compound, D-cycloserine, that has proved extremely promising in psychotherapy aimed at extinguishing phobias.

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