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For neuroscientist Joseph LeDoux, advancing the science of neural threat processing requires not only looking beyond the amygdala but also differentiating between the brain's chemical reaction to threat and our conscious experience of fear.

When global organismic states [such as threat response] are witnessed by consciousness, we interpret them with the label fear, says LeDoux, director of the Emotional Brain Institute at NYU and a member of the Dana Alliance for Brain Initiatives. Fear is a concept, not a 'thing' in the brain. Yet we assume we can find human fear in a rat brain, which is ridiculous.

Instead, LeDoux says, animal studies should focus on exploring brain mechanisms that detect and respond to threat and which might work similarly in humans. Otherwise, we risk applying flawed data to drug development. We expect too much from animal research, LeDoux says. When we find a drug that releases rats from freezing behavior when exposed to a threat, for example, we interpret that as a drug able to curb anxiety in humans. But rats don't experience 'anxiety,' at least not that we know of. That's a social construct.

A growing number of researchers are heeding LeDoux, focusing on the underlying neural mechanisms that give rise to fear and fear-related disorders. DeLaRosa's study that found evidence for frontal lobe activity in the brain's threat response, for example, broke new ground by controlling for arousal--the degree to which a person finds something to be threatening--which tends to vary widely. Doing so allowed her to focus more exclusively on the brain's response to threat to establish a baseline model against which cases of abnormal threat response can be measured.

A person with PTSD or an anxiety disorder is essentially over-responding to a frightening stimulus, DeLaRosa says. The more complete our model of how threat response works in 'normal' brains, the better able we'll be to pinpoint what's gone wrong in people who respond abnormally to threats.

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