Researchers at New York University and Princeton University have mapped out how the brain responds to situations that once generated fear, but are subsequently seen as safe or non-threatening. The research, which appears in the Journal of Neuroscience, may enhance our understanding of how to treat clinical fear disorders such as post-traumatic stress disorder (PTSD).

Previously, scientists have explored the processes by which we eliminate fears-i.e., fear extinction. In this case, the brain responds to dangerous or threatening circumstances, then alters this processing when identical situations, experienced later, are seen as safe. However, in everyday life, fear is usually not eliminated but is rather targeted somewhere else -a process called fear reversal. Fear reversal is regarded as a more demanding neurological process than is fear extinction because the brain is telling itself to not be afraid of something it formerly viewed as threatening, but at the same time to be afraid of something it formerly viewed as safe-think Linda Hamilton’s reaction to Arnold Schwarzenegger’s cyborg, which terrorized her in “The Terminator,” when she again crosses its path in “Terminator 2”. In the sequel, Schwarzenegger’s cyborg was the “good guy” and another cyborg, transformed as a police officer, turned out to be the evil one. Throughout the sequel, Sarah Connor performed a reversal of fear.

In this study, the researchers found that fear reversal is mediated through a widespread neurological network, including the brain’s amygdala, striatum, and ventral medial prefrontal cortex (vmPFC), that readjusts fear responses after reversal. In particular, they found evidence of vmPFC activity to inhibit fear under adverse conditions in which fear is not diminished but rather is reassigned and controlled. Interestingly, the researchers concluded, it appears that the brain distinguishes safe stimuli that previously predicted danger from regular safe stimuli that are just ignored. In other words, although behaviorally we respond to all safety cues with the same ease, those that were once threatening are encoded differently in the brain.

The study’s authors included researchers in NYU’s Center for Neural Science: Daniela Schiller, a post-doctoral fellow; Ifat Levy, a post-doctoral fellow; Professor Joseph LeDoux; and Professor Elizabeth Phelps, who also holds an appointment in NYU’s Department of Psychology. Professor Yael Niv of the Princeton Neuroscience Institute was also a co-author of the research.

The work marks the first detailed analysis of the components of reversal learning in humans.

“Understanding reversal learning is potentially relevant to the treatment of clinical fear disorders such as PTSD because it may serve as a tool to study the inappropriate control of fear in anxiety disorders,” the researchers wrote. “The added value of these results is they allow an examination not only of how fear responses are diminished, but also of how they are maneuvered from one stimulus to another without developing either a generalized fear response or perseveration of fear.”

In conducting the study, human subjects received one of two stimuli-two different images of faces (Face A and Face B). In order to generate “fear” and “safe” responses, some of those viewing Face A at first experienced a mild electric shock while some of those viewing Face B did not. To determine how the brain reacts when circumstances change from fear to safe and vice versa, subjects were subsequently shown the same images. However, under this condition, those viewing Face A did not experience the mild electric shock while those viewing Face B did. The researchers used functional neuro-imaging and skin conductance responses to measure subjects’ reactions.

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