Fear and Anxiety: Implications for Treatment

Individuals with bilateral damage to the amygdala can still feel fear.

NEW YORK—Chronic pain is associated with a number of comorbidities, including fear and anxiety. Therefore, understanding the neural basis of these modalities may help develop improved treatments for chronic pain.

Fear avoidance has been implicated in the transition from acute to chronic pain. In this model, conditioning contributes to the perpetuation of pain, and it is thought that disruption of conditioning would lead to the path of recovery.

At a recent conference on “Emotion and the Brain” at New York University, Joseph LeDoux, PhD, director of the Emotional Brain Institute, Nathan Kline Institute, and professor at the Center for Neural Science and Department of Psychology at New York University, began his talk by stating: “We live in our heads – the world that we experience is all inside, and we have to recognize the importance of these kinds of subjective experiences.”1

Fear –-be it of pain or any other event—is a major driver for people to seek psychological or psychiatric help. Therapy success is judged by whether patients’ feelings are under control. The subjective experience aspect of fear that is often disregarded by researchers needs to be addressed, Dr LeDoux emphasized.

It has long been accepted in the field of psychiatry that the subjective experience of fear and anxiety does not correlate well with behavioral and physical responses. Yet, those responses are often used to study fear, he pointed out.

Imaging and brain lesion studies have shown that damage to the amygdala abrogates behavioral and physical responses to threat in animals and humans, strongly implicating the amygdala as the source of fear in the brain. Some neuroscientists have argued that all that needs to be understood is how the amygdala controls fear responses.

Two major views of the mechanisms of fear have been adopted by scientists: the non-subjective state or “central state view,” in which a physiological state labeled fear connects threats with responses; and the “subjective state view,” where the actual experience of fear is in the sequence between the stimulus and the response.

A distinction that few people make, when referring to fear, leading Dr LeDoux to call it a “recipe for confusion.” Dr LeDoux recently reported his views on the subject in an article published in the American Journal of Psychiatry.2

When an article published in Nature Neuroscience reported that individuals with bilateral damage to the amygdala could still feel fear, the scientific community was forced to rethink the role of this structure in fear.3

Dr LeDoux cautioned against invoking consciousness to explain phenomena in animals that do not require conscious awareness in humans. “As neuroscientists, we can account for everything that goes on in so-called fear conditioning,” he said. However, we should call it “threat conditioning,” and avoid mentioning the word fear.

“All we need is cells and synapses that wire in the conditioned stimulus (CS), by virtue of its connection with the unconditioned stimulus (US), into the amygdala. That connection then allows the stimulus to get through and produce the responses,” he explained.

“Fear is not relevant to any of that…This does not mean that fear is an irrelevant construct, it is just not what is driving the response, and it does not mean that the responses that we study in animals are not important, they contribute to fear – they just are not one and the same as fear,” he added.

Instead of referring to the amygdala as a fear center, a more neutral way to think about it, according to Dr LeDoux, is as a structure that detects threats and controls responses to those threats. “The bottom line is, fear does not occur in the amygdala and does not cause the responses to threat. Once one is conscious that a threat is there, there may be some top-down conscious control over responses. It is not that the feeling of fear never contributes to behavioral responses, but rather, that it is not what is driving these responses in the laboratory experiments,” he said.

“This conflation of fear with processes that detect and respond to danger has hijacked our understanding of the more fundamental processes and diminished our understanding  of fear itself,” Dr LeDoux said. “We need a scientific view of how organisms detect and respond to danger that first of all recognizes the difference between the processes that detect and respond to threats, and processes that give rise to conscious experience,” he added.

According to Dr LeDoux, a fear CS should be termed a threat CS; a fear response a defense response; and fear conditioning threat conditioning. It is not about getting rid of fear, said Dr LeDoux, but rather about studying the correct modality.

“We need this conception of fear and anxiety that recognizes the importance of innate circuits that have been inherited from animals, but that does not confuse those circuits with circuits that underlie fear and anxiety. To treat problems of fear and anxiety, both kinds of circuits have to be changed, but possibly, using different treatments,” Dr LeDoux noted.

He continued to explain that the difference between an emotional and a non-emotional experience is that the mechanisms of consciousness receive distinct inputs, and process information in a different manner. Some of the signals involved in the activation of the survival circuits (eg, arousal systems, body feedback, long-term explicit and implicit memories, and expectations) get registered as working memory; out of their coalescence comes the experience of fear.

“Fear is a cognitive event, not an innate feeling inherited from animal ancestors, and these defensive survival circuits would have been inherited. Fear is not tied to a specific circuit in the brain, it is an experience you have when you are in some kind if danger, regardless of the nature of that danger,” Dr LeDoux concluded.

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1. LeDoux JE. The language of emotion and why it matters. Presented at: Cell Press LabLinks: Emotion and the Brain. New York, NY; October 13, 2016.

2. LeDoux JE, Pine DS. Using Neuroscience to Help Understand Fear and Anxiety: A Two-System Framework. Am J Psychiatry. 2016; doi: 10.1176/appi.ajp.2016.16030353.

3. Feinstein JS, Buzza C, Hurlemann R, et al. Fear and panic in humans with bilateral amygdala damage. Nat Neurosci. 2013;16(3):270-272.

This article originally appeared on Clinical Pain Advisor