Review of Medical Physiology - William F. Ganong 2002

Functions of the Nervous System
Neural Bases of Instinctive Behavior and Emotions
Fear and Rage

The connection between the Limbic System and emotions such as fear and rage was first discovered by Kluver and Bucy, who demonstrated that bilateral temporal lobectomy in monkeys results in a characteristic cluster of behavioral abnormalities (Klüver-Bucy syndrome). Following the extirpation of the limbic structures within the temporal lobe, the animals became placid, developed visual agnosia (see Chapter 16), and, in males, exhibited hypersexuality. The animals would repeatedly pick up and handle various objects, obediently complying with commands to manipulate them, chew, lick, and bite them, and then discard them if inedible, only to pick them up again shortly afterward as if they were entirely new.

Fear and rage are somewhat interrelated emotions. The external manifestations of fear, flight, or avoidance reactions in animals include autonomic responses such as sweating and pupillary dilation, crouching, and turning the HEAD in search of an escape route. Rage, fighting, or attack reactions in cats are associated with hissing, spitting, purring, piloerection, pupillary dilation, and precisely targeted biting and scratching. These reactions, or sometimes a combination of them, can be triggered by hypothalamic stimulation. When threatened, an animal will typically attempt to flee; when cornered, it prepares to fight. Thus, fear and rage are evidently interrelated subconscious defensive responses to environmental hazards.

Fear

The fear reaction in conscious animals can be elicited by stimulation of the Hypothalamus and amygdaloid nuclei; conversely, this reaction and its autonomic and endocrine manifestations cannot be induced if the amygdalae are destroyed. A striking example of this is how monkeys react to snakes. Normally, monkeys are terrified when they see snakes. However, following bilateral temporal lobectomy, they approach reptiles without fear, pick them up, and may even eat them.

There is a strong likelihood that the amygdaloid nuclei are involved in encoding fear-related memory information. Fear conditioning is blocked if neurotransmitter release (see Chapter 4) is interrupted along the pathways to the amygdala. In humans with damage to the amygdala, fear responses to auditory and visual stimuli become impaired. In healthy individuals, the sight of a fearful facial expression activates the left amygdala. The degree of this activation is proportional to the intensity of the perceived fear depicted on the face. Happy faces do not elicit such a response.

Sensory impulses that trigger conditioned emotional responses of fear may project directly to the amygdala, bypassing the sensory areas of the neocortex.

Anxiety

Anxiety is a normal emotion occurring in appropriate situations; however, excessive anxiety, as well as anxiety in inappropriate situations, can have detrimental consequences. In humans, the feeling of anxiety is accompanied by a bilateral increase in Blood flow within a restricted area of the anterior pole of each temporal lobe. Benzodiazepines alleviate this sensation. They bind to GABA receptors and enhance Cl^- conductance through these Ion Channels. Patients with anxiety disorders exhibit reduced sensitivity to benzodiazepines. These substances bind to the subunits of GABA receptors. However, the γ₂ subunit must also be sufficiently sensitive to benzodiazepines. Mice heterozygous for a γ₂ subunit knockout show a decreased response to this drug and display heightened anxiety behaviors. These animals can be used to investigate the causes and Treatment of panic disorders in humans.

Rage and Placidity

In most animals, as well as in humans, a balance is maintained between rage and the opposite state, which can be characterized as placidity. Moderately strong stimuli significantly affect a normal individual, whereas weak stimuli are ignored. In animals with Brain lesions, this balance is disrupted. Some lesions produce a state in which minor stimuli provoke violent fits of rage, while others result in a state where even the most distressing and provocative stimuli fail to disturb an abnormally calm individual.

Rage reactions to minor stimuli are observed following the extirpation of the neocortex or the destruction of the ventromedial and septal nuclei in animals with an intact cortex. On the other hand, bilateral destruction of the amygdaloid nuclei in monkeys produces a state of abnormal placidity, which can turn into rage following subsequent ablation of the ventromedial nuclei of the hypothalamus. Rage can also be elicited by stimulating the pathway running from the lateral hypothalamus to the periaqueductal gray of the Midbrain.

Aggressive behavior is influenced by Sex Hormones. In male animals, aggressiveness decreases following castration and increases under METABOLISM/18.html">The Influence of androgens. Social factors also play a role; aggressiveness is more pronounced in men living with women and increases in the presence of a rival.

Sham Rage

It was previously believed that rage attacks in animals with lesions of the Diencephalon and Forebrain were merely physical, motor manifestations of anger, and they were therefore termed "sham rage." However, this view is incorrect. Although rage attacks in animals with diencephalic lesions are induced by minor stimuli, they are typically very accurately directed toward the source of irritation. Furthermore, hypothalamic stimulation that triggers the fear-rage response is clearly unpleasant to animals, as they are reluctant to return to the place where such experiments are conducted and attempt to avoid the Procedure. Animals readily learn to press a lever or perform another action that allows them to avoid hypothalamic stimulation. It is very difficult or even impossible to establish conditioned responses (see Chapter 16) by stimulating the motor system alone, nor can this be easily achieved unless the unconditioned stimulus evokes either a pleasant or unpleasant sensation. The fact that hypothalamic stimulation acts as an unconditioned reinforcer in establishing conditioned avoidance responses, and that avoidance responses are extremely persistent, indicates that the stimulus is aversive. Therefore, there is little doubt that rage attacks involve both psychic and physical components, rendering the term "sham rage" a misnomer.

Clinical Aspects

Although emotional reactions in humans are more complex and subtle than in animals, their neural substrates are presumably the same. Placidity is hardly to be classified as a clinical syndrome, but fits of rage triggered by minor everyday annoyances can be observed in patients with brain lesions. These attacks occur as a complication of pituitary surgery if there is inadvertent damage to the Base of the brain, and they may also accompany a variety of Nervous system disorders, notably epidemic Influenza and encephalitis, which damage the Neurons of the limbic system and hypothalamus.