"Is emotion a magic product, or is it a physiological process which depends on an anatomic mechanism?" (Papez, 1937)

Limbic system
During the evolution of the amphibians and reptiles, a number of three-layer cortical structures developed, sheathing the periphery of the brainstem. With the subsequent growth of the neocortex, they became sandwiched between the new and the old brain. These structures are known as the Limbic system, and are a set of subcortical structures that form a border (or limbus) around the brain stem. The Limbic System includes: cingulate gyrus, thalamus, fornix, hypothalamus, mamillary body, hippocampus, amygdala and olfactory bulb.

Early Research
Originally, neuroanatomists recognized the connections between the olfactory system (smell) and the limbic system. Based on this, it was suggested that the limbic structures dealt primarily with olfactory information, and were known as the rhinencephalon, or smell-brain. Further experimentation found that the limbic system had little olfactory function, and the limbic system lay in "scientific limbo" for a time (Kolb & Whishaw, 1990).

Philip Bard (1929, 1934) found that when he removed the entire cerebral cortex of cats, they displayed exaggerated aggressive behaviors and postures in response to various stimuli. Evidently, subcortical areas could generate emotional behaviors; the function of the cerebral cortex was to direct those behaviors toward appropriate targets and, when appropriate, the suppress them.

There have been many attempts to link emotional processes to neuroanatomical structures, beginning with Papez (1937) (rhymes with grapes) who identified the limbic system structures as controlling emotion. He suggested that the emotional brain consisted of a circuit in which information flowed from the mamillary bodies in the hypothalamus to the anterior thalamic nucleus, to the cingulate cortex, to the hippocampus and back to the mamillary bodies. Input could also enter this circuit from other structures to be elaborated as emotion. Although this is now thought to be an oversimplification of the function of the limbic system, the belief remains that it plays a role in emotions (Kolb & Whishaw, 1990).

Paul MacLean (1949, 1958, 1970) revised Papez's theory, and calling the circuit of Papez the limbic system. Because the size of the limbic system is relatively constant in size across mammalian species, in contrast to the cortex which varies greatly in size, he concluded that the limbic system control primitive functions that all mammals share in common. Much of his research was conducted on those with head injuries and temporal lobe epilepsy, since emotional disturbances are often seen in each.

MacLean (1970) distinguished three limbic circuits. One circuit, including the amygdala and hippocampus, affects behaviors related to self-preservation. Damage to various parts of the amygdala can make an animal excessively tame, unaggressive, and emotionally unresponsive. Monkeys and cats with amygdala damage sometimes attempt to eat feces, burning matches and other objects that they would ordinarily reject. The second circuit includes the cingulate gyrus, the septum, and several other structures. This circuit seems to relate to pleasure, especially sexual enjoyment. Electrical or chemical stimulation of this region in rats often causes penile erection, self-grooming and related behaviors. The third circuit includes parts of the hypothalamus and anterior thalamus, and is believed to be important for cooperative social behavior and certain aspects of sexuality.

The major areas of the Limbic system and their functions will be described in detail below.
(Figure caption: A more functional approach to the limbic structures.)

  Hypothalamus

The hypothalamus has widespread connections with the rest of the forebrain and the midbrain, and contains a number of distinct nuclei. Damage to one of the hypothalamic nuclei leads to abnormalities in one or more motivated behaviors, such as feeding, drinking, temperature regulation, sexual behavior, fighting or activity level. The hypothalamus also plays a role in emotions. Specifically, the lateral portion is involved in pleasure and rage, the medial portion is involved with aversion, or unpleasure, uncontrolled laughter and rage (Beekmans & Michiels, 1996).

The hypothalamus also regulates the secretion of hormones through its effects on the pituitary gland, which is attached to the base of the hypothalamus by a stalk that contains neurons, blood vessels and connective tissue. The pituitary gland responds to messages from the hypothalamus, and synthesizes and releases hormones into the bloodstream. Its secretions control the timing and amount of hormone secretion by the other endocrine organs, such as the thyroid, adrenal glands, and ovaries or testes (Kalat).

Amygdala
The amygdala, (which means "almond-shaped"), is buried within the anterior-inferior temporal lobe, and is "preeminent in the control and mediation of all higher order social-emotional activities such as friendliness, love and affection." It is also involved with fear, rage and aggression.

Bilateral lesion of the amygdala disturbs the ability to determine and identify the motivational and emotional significance of externally occurring events, to discern social-emotional nuances conveyed by others or to select what behavior is appropriate for a specific social context (Klüver & Bucy, 1939). (Beekmans & Michiels, 1996). Electrical stimulation of the amygdala in cats can lead to vigorous affective (emotional) attacks. [insert quicktime move "RAGE" about here].

Rabies (Latin term for rage), a disease caused by a virus that attacks much of the brain but especially the temporal lobe (including the amygdala) leads to furious, violent behavior. Damage to the amygdala can change how an animal interprets information. Male cats with amygdala lesions may sexually mount other males, members of other species, or even inanimate objects. Their total sexual activity does not increase, but they become indiscriminate in the selection of partners. Similarly, certain monkeys with amygdala lesions have trouble interpreting social stimuli from other monkeys; because of their misinterpretations, they may attack inappropriately or fail to defend themselves when attacked.

Hippocampus. The hippocampus (from a Latin word meaning sea horse) is located within the inferior medial wall of the temporal lobes, between the thalamus and the cortex, toward the posterior of the forebrain. It consists of two major axon tracts, the fornix, and the fimbria, which link the hippocampus with the hypothalamus and several other structures.

(The fornix was named after an ancient Roman arch that was a famous gathering place for prostitutes. That arch also gave us the word fornication) (Kalat). The hippocampus plays major role in memory and learning, but not in emotions. However, Loenthal and Trabasso (1990) observed anxiety and aggression when the hippocampus is directly electrically stimulated.

A more detailed discussion of the hippocampus' role in memory will be discussed in the following lecture.

Limbic System Disorder

Temporal Lobe Epilepsy
An epileptic attack occurs when a large group of neurons suddenly produce synchronous action potentials. When this occurs in the temporal lobe, symptoms can include hallucinations, lip smacking or other repetitive acts, and emotional behaviors. Although most people with epilepsy have no particular emotional experiences with their seizures (ictally), a substantial minority experience aggressive impulses, fear, a dissociation of experience similar to multiple personality, uncontrollable laughter, sexual arousal, or a feeling of extreme bliss including a sense of oneness with the universe (Kalat).

Emotional disturbances can also occur between seizures (interictally) in those temporal lobe epilepsy. At one time, there was thought to be an "interictal behavior syndrome" which was unique to epilepsy, and caused changes in personality and emotional functioning. Although researchers now understant that there is no epileptic personality, there are many characteristics which have been attributed to temporal lobe epileptics. (insert Chart 1 - TLE).

Case Example (Mark & Ervin, 1970):
Thomas was a 34-year-old engineer, who, at the age of 20, had suffered a ruptured peptic ulcer. He was in a coma for 3 days, which caused some brain damage. Although his intelligence and creativity were unimpaired, there were some serious changes in his behavior, including outbursts of violent rage, sometimes against strangers and sometimes against people he knew. Sometimes his episodes began when he was talking to his wife. He would then interpret something she said as an insult, throw her. He would then interpret something she said as an insult, throw her against the wall and attack her brutally for 5 or 6 minutes. After one of these attacks he would go to sleep for a half hour and wake up feeling refreshed.

Eventually he was taken to a hospital, where epileptic activity was found in the temporal lobes. For he next seven months, he was given a combination of tranquilizers, and antiepileptic medications. None of these treatments reduced his violent behavior. He had previously been treated by psychiatrists for 7 years without apparent effect. Eventually he agreed to a surgical operation to destroy a small part of the amygdala on both sides of the brain. Afterwards he had no more episodes of rage.

Klüver-Bucy Syndrome:
A syndrome which was originally noted by Brown and Schaefer in 1888 was rediscovered be Klüver and Bucy in 1939. It results from the bilateral removal of the amygdala and inferior temporal cortex and includes:
(1) tameness and a loss of fear;
(2) indiscriminate dietary behavior;
(3) greatly increased autoerotic, homosexual, and heterosexual activity, with inappropriate object choice;
(4) hypermetamorphosis, or a tendency to attend to and react to every visual stimulus;
(5) a tendency to examine all objects by mouth;
(6) visual agnosia, or the inability to recognize objects visually. The syndrome has also been found to be due to meningoencephalitis (inflammation of the brain and the meninges).

Korsakoff's Syndrome: Korsakoff's syndrome is a severe anterograde amnesia. This means that those with the syndrome cannot form new memories, although they can still remember old ones. They can converse normally and can remember events that happened long before their brain damage occurred, but they cannot remember events that happened afterward. Korsakoff's syndrome results from a thiamine (vitamin B1) deficiency, usually caused by alcoholism. Because alcoholics receive a substantial number of calories from the alcohol they ingest, they usually eat a poor diet, so they have a decreased absorption of thiamine. Postmortem examination of the brains of patients with Korsakoff's syndrome almost always reveal severe degeneration of the mamillary bodies. (Figure caption: Degeneration of the mammillary bodies in a patient with Korsakoff's syndrome. A. D'Agostino, Good Samaritan Hospital, Portland, Oregon.)

Autism (Edelson, S. Center for the Study of Autism, Salem, Oregon)
Over the past 10 years, high-tech research methods have begun to reveal neurological damage in some autistic individuals. One of the most important findings indicates specific damage in the limbic system, particularly in the amygdala and hippocampus. Much of this research has been conducted by Dr. Margaret Bauman, (Dept. of Neurology, Harvard Medical School), and Dr. Thomas Kemper, (Depts. of Neurology, Anatomy, and Pathology, Boston University School of Medicine). They report densely packed neurons in the amygdala and hippocampus of persons with autism. Additionally, they note that these neurons are smaller than in normal persons. At this time, we do not know what causes neurological damage in these areas; however, the damage appears to occur during the prenatal stage of development. Can damage in the amygdala and hippocampus explain some of the behaviors exhibited by autistic children and adults? We can only speculate at present, but it is interesting to theorize about the possible connections between damage in the limbic system and the characteristic traits of many autistic people. Much of what we know of the behaviors associated with the amygdala and hippocampus are based on animal research. In these studies, researchers either surgically damage or remove a specific area in the brain and then observe any changes in the animal's behavior.

The amygdala controls our aggression and emotions. Many autistic individuals are aggressive towards themselves or others, or conversely, extremely passive. Furthermore, autistic children and adults often appear emotionless or 'flat' (even though they obviously do have emotions). Experimenters have also shown that when the amygdala is removed or damaged, animals exhibit behaviors similar to autistic individuals, such as social withdrawal compulsive behaviors, failure to learn about dangerous situations, difficulty retrieving information from memory, and difficulty adjusting to novel events or situations. In addition, the amygdala is responsive to a variety of sensory stimuli, such as sounds, sights, and smells; as well as emotionally or fear-related stimuli. We know that autistic individuals often have problems with each of these senses. Interestingly, Georgie, whose childhood was described in her mother's book, The Sound of a Miracle, often mentioned being afraid of many sounds prior to receiving auditory integration training from Dr. Guy Berard.

The hippocampus appears to be primarily responsible for learning and memory. Damage or removal of the hippocampus will lead to an inability to store new information into memory. This sounds similar to Dr. Bernard Rimland's cognitive theory of autism. In his 1964 award-winning book Infantile Autism, Dr. Rimland theorized that autistic children had difficulty relating new information to previously stored information. In addition, when the hippocampus is damaged or removed, animals will display stereotypic, self-stimulatory behaviors and hyperactivity.

Although one can easily speculate about a relationship between the limbic system and autistic behaviors, we should be conservative, because much of what we know comes from animal models in which the parts of the limbic system are damaged artificially. We need to be cautious in extrapolating these findings to autistic individuals. However, the correspondence between behaviors seen in autism and what we know of the limbic system is compelling.

Hunger and Satiety
In the 1940's and 50's, investigators found that damage to the lateral hypothalamus decreased eating and that damage to the ventromedial hypothalamus increased eating. Their initial interpretation was that the lateral hypothalamus controlled hunger and that the ventromedial hypothalamus controlled satiety. It became clear, later, that brain damage can affect feeding in many ways other than simply bo controlling hunger and satiety. For example, it can alter activity levels or it can alter the activity of the autonomic nervous system and thus change the activity of the digestive organs.

Damage to the lateral hypothalamus leads an animal to refuse food and water, and the animal may starve to death unless it is force-fed. Electrical stimulation of the lateral hypothalamus causes an animal to eat. In addition to not eating, damage to the lateral hypothalamus also causes animals to be underaroused, underresponsive to sensory stimuli, and inactive.

The lateral hypothalamus stimulates the release of insulin and digestive juices in the stomach. The hormone insulin facilitates the entry of glucose into the cells, which may either use the glucose for current energy needs or store it as fat or glycogen. Generally, when insulin levels are higher, hunger is low. After damage to this brain area, an animal has low levels of insulin and digestive juices, so it has difficulty digesting its food, and little motivation to do so because its fat reserves are being converted into blood glucose, in response to the drop in insulin levels.

The ventromedial hypothalamus is located adjacent to the lateral hypothalamus. Damage to it, including axons passing through and around it, produce effects that are nearly the opposite of those produced by damage to the lateral hypothalamus. The animal eats and drinks excessive amounts and gains weight. The size of each meal may be normal, however it is the frequency of eating which increases substantially. This is due to the fact that their stomachs empty faster than those of other rats, particularly during daylight hours. Also, a lasting increase in insulin production results from the damage. Rats will have higher than normal insulin levels at all times and respond to meals with even larger insulin increases. Because of the increased insulin, a larger than normal percentage of each meal is stored a s fat. In fact, if such animals are prevented from overeating, they will still gain weight. Thus, the animal does not gain weight because it overeats, rather it has to overeat because it stores excessive fat. It has no more usable fuel in its bloodstream than a starving animal has. What it eats is largely converted to fat; to have enough fuel for its current use, it must continue to eat.

Other changes which occur with damage to the ventromedial hypothalamus include:
1. They drink excessive amounts of water.
2. They are less responsive than normal rats are to the satiating effects of glucose.
3. They are finicky eaters, in that they overeat more on a particularly tasty diet.
4. Although they overeat when food is readily available, they will not work as hard as normal rats to get food.

Neurotransmitters also play a role in eating. The lateral hypothalamus and probably other hypothalamic areas release tiny quantities of dopamine and serotonin. The dopamine may be important for the reward value of eating; its release is closely correlated with how hard the animal will work for food. The serotonin apparently contributes to ending the meal.

Temperature Regulation
The preoptic area of the hypothalamus, a nucleus adjacent to the anterior hypothalamus, is critical for temperature control. The preoptic area monitors body temperature partly by monitoring its own temperature. When the area is heated experimentally, the animal pants or sweats, even in a cool environment. The animal will even learn to press a lever or to do other work for cold air reinforcements. The opposite is true if the preoptic area is cooled.

The preoptic area also receives input from temperature-sensitive receptors in the skin and spinal cord. Damage to the area impairs a mammal's temperature regulation. It can no longer shiver, so its body temperature plummets in a cold environment. Even in a steady environment, the animal's body temperature can fluctuate over a range of 10 degrees or more. Other areas of the hypothalamus, brain and spinal cord are also implicated in temperature control.

Drinking
The lateral preoptic area of the hypothalamus plays a large role in thirst and drinking. If a drop of concentrated salt solution is applied directly to the area, the animal will soon begin to drink. However, if distilled water is applied, the animal stops drinking. Thus, cells in this area sense their own state of hydration, just as the cells that control temperature monitor their own temperature. A lesion in the lateral preoptic area decreases a rat's drinking response to an injection of sodium chloride into the blood. The rat is still able to restore its balance, but does so using a different strategy.

Sexual Function
The hypothalamus controls the pituitary gland, which consists of the anterior and posterior pituitary, which release different sets of hormones. The posterior pituitary, composed of neural tissue, can be considered an extension of the hypothalamus. Cells in the hypothalamus synthesize two hormones, oxytocin and vasopressin (also known as antidiuretic hormone) and then transport then to the posterior hypothalamus. The posterior pituitary stores these hormones until stimulated to release them.

The anterior pituitary, composed of glandular tissue, synthesizes six hormones itself, however the hypothalamus controls their release. The hypothalamus secretes releasing hormones, which flow through the blood to the anterior pituitary. There they stimulate or inhibit the release of six known hormones, five of which control the secretions of other endocrine organs. These six hormones are:

Adrenocorticotropic hormone (ACTH)	Controls secretions of the adrenal cortex
Thyroid-stimulating hormone (TSH)	Controls secretions of the thyroid gland
Follicle-stimulating hormone (FSH) Luteinizing hormone (LH)	Controls secretions of the gonads
Prolactin	Controls secretions of the mammary glands
Somatotropin (growth hormone (GH))	Promotes growth throughout the body

The hypothalamus maintains fairly constant circulating levels of certain hormones. For example, when the level of thyroid hormone is low, the hypothalamus releases one of its hormones, known as TSH-releasing hormone, which stimulates the anterior pituitary to release TSH, which in turn causes the thyroid gland to secrete more thyroid hormones. After the level of thyroid hormones has risen, the hypothalamus decreases its release of TSH-releasing hormone.

Menstrual Cycle
In women, the hypothalamus and pituitary interact with the ovaries to produce the menstrual cycle. At the beginning of the menstrual period, follicle-stimulating hormone (FSH) promotes the growth of follicles in the ovary. Toward the middle of the cycle, the follicles produce increasing amounts of one type of estrogen, estradiol, which inhibits the release of luteinizing hormone (LH). However, near the middle of the cycle, the increase in estrogen levels causes a sudden surge of LH and FSH release, which causes one of the follicles in the ovary to release an ovum (egg), and they prepare the uterus for implantation of a fertilized ovum. If the ovum is not fertilized, the lining of the uterus is cast off, and the cycle can begin again.

Limbic Links

http://www.tech.plym.ac.uk/soc/research/neural/research/rats.htm
http://www.amenclinic.com/brain.htm#limbic (Neuropsychiatry of Limbic System)
http://www.songweaver.com/brain/ (The Components of the Human Brain)
http://www.indiana.edu/~pietsch/home.html (How does the brain house the mind?)
http://www.autism.org/limbic.html (Autism and the limbic system)
http://www.coastside.net/USERS/runner/articles/nerves.html (anectodtal stuff about the limbic system)