Biology 202
1998 Second Web Reports
On Serendip

The Role of the Amygdala in Fear and Panic

Doug Holt

The definition of fear has proved to be an elusive mystery plaguing scientists. While there is much agreement as to the physiological effects of fear, the neural pathways and connections that bring upon these effects are not well understood. From the evolutionary standpoint, the theory is that fear is a neural circuit that has been designed to keep the organism alive in dangerous situations (1). How does it all work? Learning and responding to stimuli that warn of danger involves neural pathways that send information about the outside world to the amygdala, which in turn, determines the significance of the stimulus and triggers emotional responses like freezing or fleeing as well as changes in the inner workings of the body's organs and glands (1). There are important distinctions to make between emotions and feelings. Feelings are "red herrings", products of the conscious mind, labels given to unconscious emotions (2) whereas emotions are distinct patterns of behaviors of neurons. Emotions can exist of conscious experiencesas well as physiological and neurological reactions and voluntary and involuntary behaviors (3). But the components of fear goes beyond feelings and emotions. It is also the specific memory of the emotion. After a frightful experience, one can remember the logical reasons for the experience (e.g. the time and place) but one will also "feel" the memory, and his body will react as such (i.e. increased heart and respiration rate, sweating). In one recent case, after a near drowining incident, the victim could not only vividly remember each detail, but when doing so, his body reacted as though he were reliving the experience. These feelings of memory are stored in an almond shaped structure in the brain known as the amygdala.

The amygdala is the name of the collection of nuclei found in the anterior portions of the temporal lobes in the brains of primates (4). The amygdala receives projections from frontal cortex, association cortex, temporal lobe, olfactory system and other parts of the limbic system. In return, it sends its afferents to frontal and prefrontal cortex, orbitifrontal cortex, hypothalmus, hippocampus, as well as brain stem nuclei (20). After this point, neither the concrete definition as to the extent of the amygdala is not clear, nor is the exact function of each of its subgroups. In the amygdala region alone, there is much controversy surrounding the nuclear subgroups, resulting in classifications that range between 5 and 22 different groups within the amygdala itself. Despite all of this, there are four main groups that have been universally agreed upon. These are the Basolateral, Lateral, Central, and Basomedial nuclei. The amygdala is considered to be the key component to the limbic system, a term that has also been regarded with much recent controversy by researchers in the field of emotions. One of the biggest surprises from LeDoux's work is that there may be no such thing as the limbic system – a brain structure that has been supposed to underlie emotion and motivation. "All students are taught about the limbic system," LeDoux said, "but in my opinion, it's no longer a valid concept." (2) Reasons for his assertations center around the investigations of the mechanisms by which the amygdala processes information regarding threats and fear. The classic model of the limbic system encompasses the hippocampus, the amygdala, and a few other small structures. These structures supposedly receive sensory input from the outside world – sight, smell, hearing, touch, and taste, as well as from the viscera. When these sensations are integrated in the limbic system, emotional experiences are thought to occur (2). While the fear circuit does indeed appear to incorporate the amygdala, the hippocampus and the other limbic structures are not involved. They are bypassed in the fear circuit. But fear and its emotional memories are not the only things controlled by the amygdala. The amygdala has up to 22 distinct regions and only two so far have been clearly implicated in fear (2). The flight and fear responses may be obtained from the rostral regions of the amygdala, including the lateral nucleus, the periamygdaloid area, and the central nucleus. Defense or aggressive reactions could be obtained from the medial and caudal aspects of the amygdala (4). These reactions have been observed by the selective stimulation of amygdaloid nuclei in laboratory animals.

In a related process, another responsibility of the amygdala is the suppression of the periaqueductal gray. The periaqueductal gray is another major structure involved in the interpretation of fear. It is a large structure in the midbrain, consisting of small to medium neurons surrounding the aqueduct of Silvus, otherwise known as the cerebral aqueduct. The periaqueductal gray is thought to be involved in protection and defensive reactions (15), notably distress calls and affective defense. Affective defense is characterized, for example, in cats by unsheathing of claws, baring of teeth, hissing, piloerection, paw striking, and arching of the back (15). When selectively electrically stimulated, the amygdala suppresses these behaviors and causes freezing. Freezing is a robust index of learned fear (16).

What is known about the amygdala is that it has a dual sensory input system. Both inputs run from the eyes, ears, and other sense organs to the thalamus. At that point the inputs diverge. One pathway leads directly to the amygdala while the other first passes through the cortex. Each input causes a distinct and specialized behavior. The amygdala is specialized for reacting to stimuli and triggering a physiological response, a process that would be described as the "emotion" of fear (2). After this, the stimuli of the activation of the amygdala is transmitted to the cortex. This is a distinct difference from a conscious feeling of fear. Feelings are thought arise from the second, slower pathway that travels from the sensory input first to the higher cortex and then to the amygdala. In the cortex the frightening stimulus is analyzed in detail, using information from many parts of the brain, and a message is sent back down to the amygdala (2). While having both systems in place may appear to be redundant, its purpose is invaluable. The initial signal, activating the amygdala and its corresponding physiological behaviors, prepares the body for immediate reaction to the stimulus. This is part of the startle circuit. Its physiological effects are similar to the initial stages of fear. By having the body ready for action, the second circuit can then take a moment to analyze the signal in its entirety to determine whether or not the threat is real or perceived. If the threat is real, then the body is already on the go, if perceived, than nothing has been lost. But there are problems associated with the double wiring between the higher cortex and the amygdala. Unfortunately the neural connections from the cortex down to the amygdala are less well developed than are connections from the amygdala back up to the cortex. Thus, the amygdala exerts a greater influence on the cortex than vice versa. Once an emotion has been turned on, it is difficult for the cortex to turn it off (2).

Through the usage of fear conditioned rats in laboratory settings, researchers have been able to effectively map out the "fear circuit". The fear circuit is stimulated in rats by means of placing the animals in metal boxes and subjecting them to foot-shocks associated with an auditory signal. This method effectively conditions the rats to fear both the metal boxes in which they had experienced pain and the corresponding auditory signal. After experiencing these stimuli, the rats, when exposed to the auditory signal, react with fear. The same fear is expressed when placed inside of the conditioning box, whether or not foot-shocks were applied. Through these experiments, it has been determined that the amygdala is required for both the fear circuit and the memory of fear (conditioned fear) associated with stimuli. These determinations were made through selective lesions of the auditory pathway through to the amygdala. Only when selective lesions were made on the amygdala, did the laboratory animals not respond to the frightening stimuli.

Occasionally, there can be debilitating problems associated with hyperactivity of the amygdala. Being the storehouse for the memory of fear, it can misinterpret signals from the body and cause inappropriate actions. This can lead to panic. Panic is a heightened stage of anxiety and fear feeding itself in a positive feedback loop and jumping to faulty conclusions, which focus on impending danger, madness, harm, or death. Physically, the body undergoes many changes that ready it for extreme action. There is a marked secretion of glucocorticoids and catecholamines which increases the blood glucose levels. Also, increase production of epinephrine and norepinephrine, which has the effect of vasodilation of blood vessels in skeletal muscles. Other symptoms of the sympatho-adrenergic stimulation involve modifications of breathing, increased temperature, localized sweating, decreased motility of the stomach, bowels, and intestines, constrictions of sphincters in the stomach and intestines, as well as piloerection (20). But the question of what generates panic attacks still remains essentially unanswered at the moment. There are many theories accorded to panic, the most prominent are:

Clark's theory on catastrophic interpretations (1988) sees panic attacks as a result of maladaptive and faulty interpretation of body signals. Beck's theory proposes a similar model, but based on predisposing and precipitating factors. Elhers' theory explains panic attacks as a result of panicogenic interoception. Barlow's theory proposes that panic attacks are modified "fight or flight" mechanisms in the absence of danger (20).

The limbic system, especially the amygdala, has long been considered to be directly implicated in anxiety and fear stages. The amygdala and its central nucleus thus communicate with many brain regions, including those that control breathing, motor function, autonomic response, release of hormones, as well as processing of interoceptive and external information (20). Therefore, the claim that the limbic system, with the amygdala and its central nucleus are implicated in panic attacks makes a biologically plausible hypothesis.

Fortunately, there are methods of reducing fear and inhibiting the fear response. Through testing with laboratory animals, it has been determined that when attention is shifted away from the anxiety-provoking stimulus, less fear is observed. When a novel stimulus is presented slightly before or at the same time as a well-trained condition stimulus, the condition response will be disrupted (18). This effect has been described using many methods but the neural mechanism is not well understood at this time. Another method of inhibiting the fear circuit is through conditioning. In a typical conditioned inhibition procedure, conditions are arranged such that one stimulus, denoted A, predicts shock, while another stimulus, denoted X, predicts absence of shock. The result of this procedure is that A comes to elicit a fear reaction when presented alone, but not when it is accompanied by X, the conditioned inhibitor (17). This is a similar method of treatment that is used for people with phobias. This method is inhibiting the emotional response produced by the amygdala during a threatening situation. The patient still remembers that he used to be afflicted by his phobia, but no longer has the emotional response attached to it (3).

There is much correlation between the emotional states of fear. Anxiety, distress, and fear are closely related negative emotional states associated with physical or psychological harm. These three emotions can be differentiated by the temporal relationship between the feeling and the potential threat. Anxiety is characterized by the anticipation of being harmed in the future, where as fear is characterized as the anticipation of being harmed in the present. Distress is characterized by the awareness of being harmed at this particular moment. The three emotions can diffuse into one single diffuse state (5).

 

Works Cited

1.) LeDoux "Emotion, Memory, and the Brain"

2.) LeDoux "Using Rats to Trace Routes of Fear"

3.) LeDoux "A Neural Model of Fear May Lead to a Better Understanding of Other Emotions"

4.) Isaacson, Robert. The Limbic System. Plenum Press, New York, NY, 1982

5.) Thompson, Jack George. The Psychobiology of Emotions. Plenum Press, New York, NY, 1988

6.) "The Main Areas Involved with Emotions"

7.) "Theories of the Role of Brain Structures in the Formation of Emotions"

8.) "Phobias: When Fear is a Disease"

9.) "Aversive Motivation"

10.) "How the Brain Feels Fear"

11.) "How the Brain Feels Fear"

12.) "Emotion: Circuit Level: The LeDoux Circuit"

13.) "Amygdala Home Page"

14.) "Research Reveals Clues to Who Suffers Panic Attacks"

15.) "The Anatomy of Fear"

16.) "Stephen Maren, Ph.D."

17.) Van Goozen, Stephanie H. M. (ed.). Emotions: Essays on Emotion Theory. Lawrence Erlbaum Associates, Publishers, Hillsdale, N.J., 1994

18.) Kavanaugh, Robert. Emotion: Interdisciplinary Perspectives. Lawrence Erlbaum Associates Publishers, Hillsdale, N.J., 1996

19.) Muller, Jeff, "Functional Inactivation of the Lateral and Basal Nuclei of the Amygdala by Muscimol Infusion Prevents Fear Conditioning to an Explicit Conditioned Stimulus and to Contextual Stimuli". Behavioral Neuroscience, Vol. 111, No. 4, pp. 683-691, 1997

20.) "Brain Structures Implicated in Panic Disorder"

"Gene That Influences Fearfulness in Mice Discovered"

"The Fear Trigger"

"Medial Temporal Lobe"

 

 

Comments made prior to 2007

This is a great summary of the origins and mechanisms of fear, anxiety and distress. These 3 harmful emotions cause amazing amounts of damage, as alluded to in the paper, and in my opinion can be linked to the harm done by bullies. In the growing concern for schoolyard, workplace, political and home based bullies and the affects on targets, it seems to me that solutions lie in the amygdala, as mentioned in the book, Emotional IQ. For the targets of bullying however, perhaps the solutions listed below, to interupt the pathway and make the stimuli less toxic, could contribute to helping targets and thus, ameliorate not only some of the physical effects, such as death, heart attack and stroke, but also cut down on the costs to society of bullies. Is evil then a dysfunction of the amygdala? Is this a center of narcissism? ... Diane White, 31 March 2006