Department of Physiology: CNS Physiology-Offline information

NSAIDs: The analgesic effect of nonsteroidal anti-infl ammatory drugs (NSAIDs) (e.g., ibuprofen) is related to inhibiting the production of infl ammatory pain sensitizers (e.g., prostaglandins and leukotrienes). By inhibiting the production of prostaglandins and leukotrienes, NSAIDs can limit the sustained hyperalgesic state induced by these pain sensitizers.

Syringomyelia is characterized by progressive cavitation of the central spinal canal, most commonly occurring in the cervical spinal cord. Anatomically, the decussating second order neurons associated with the anterolateral spinothalamic tract are in close proximity to the spinal canal, rendering them susceptible to damage early in this disease as the central canal expands. As a result, patients present with bilateral loss of pain and temperature in a “cape-like” distribution of the shoulders and upper extremities (see figure). As the cavitation progresses, motor neurons that reside in the ventral horn of the spinal cord become compressed, resulting in bilateral flaccid paralysis of the upper extremities.

Synesthesia: Individuals with a condition called synesthesia (which literally means “joined perception”) may “hear” colors, “see” sounds, or “taste” shapes. Synesthetes with “colored-hearing” may see green when they hear the word “dog,” and see red when they hear the word “cat.” They may see letters in the alphabet as always being a certain color—such as L appearing blue and N appearing orange—regardless of which color most other people perceive the letters to be. They may even taste steak when they see a triangle!. Interestingly, synesthesia seems to be an involuntary automatic phenomenon that usually works in only one direction. For example, when a synesthete sees yellow when looking at the number 5, that person will always see the number 5 as yellow, but he will not necessarily see the number 5 when exposed to the color yellow. Synesthesia also seems to run in families, and synesthetes within a family tend to have the same form of synesthesia. Outside families, the synesthesia is highly variable—for some synesthetes the number 5 is yellow, whereas for others the number 7 is yellow. Most forms of synesthesia are considered developmental anomalies in the wiring of the central nervous system. Magnetic resonance imaging (MRI) studies of colored-hearing synesthesia, for example, show that when synesthetes hear particular words, their visual association areas become active—an event that does not occur in normal individuals. This phenomenon suggests that auditory pathways in synesthetes developed connections to visual processing centers in these individuals’ brains. It is thought that normal individuals also develop such sensory pathways but that the pathways undergo apoptosis (programmed cell death). In people with synesthesia, however, the pathways persist. That synesthesia is more common in young children than adults provides evidence that these “extra pathways” degenerate during development. Synesthesia can also be induced in adults in response to brain injury or epilepsy. Because synesthesia is rare and occurs in many variants, studies on its developmental patterns are difficult to conduct and tend to yield results that are far from definitive.

Disconnection Syndrome: The functional differences between the hemispheres become apparent if the corpus callosum is cut, a procedure sometimes performed to treat epileptic seizures that cannot be controlled by other methods. This surgery produces symptoms of disconnection syndrome. In this condition, the two hemispheres function independently, each “unaware” of stimuli or motor commands that involve its counterpart. Individuals with this syndrome exhibit some rather interesting changes in their mental abilities. For example, objects touched by the left hand can be recognized but not verbally identified, because the sensory information arrives at the right hemisphere but the speech center is on the left. The object can be verbally identified if felt with the right hand, but the person cannot say whether it is the same object previously touched with the left hand. Sensory information from the left side of the body arrives at the right hemisphere and cannot reach the general interpretive area. Thus, conscious decisions are made without regard to sensations from the left side. Two years after a surgical sectioning of the corpus callosum, the most striking behavioral abnormalities have disappeared and the person may test normally. In addition, individuals born without a functional corpus callosum do not have sensory, motor, or intellectual problems. In some way, the CNS adapts to these situations, probably by increasing the amount of information transferred across the anterior commissure.

Breaching the Blood–Brain Barrier: Because it is so effective, the blood–brain barrier prevents the passage of helpful substances as well as those that are potentially harmful. Researchers are exploring ways to move drugs that could be therapeutic for brain cancer or other CNS disorders past the BBB. In one method, the drug is injected in a concentrated sugar solution. The high osmotic pressure of the sugar solution causes the endothelial cells of the capillaries to shrink, which opens gaps between their tight junctions, making the BBB more leaky and allowing the drug to enter the brain tissue. •

Injury to the Medulla Given the vital activities controlled by the medulla, it is not surprising that injury to the medulla from a hard blow to the back of the head or upper neck such as falling back on ice can be fatal. Damage to the medullary respiratory center is particularly serious and can rapidly lead to death. Symptoms of nonfatal injury to the medulla may include cranial nerve malfunctions on the same side of the body as the injury, paralysis and loss of sensation on the opposite side of the body, and irregularities in breathing or heart rhythm. Alcohol overdose also suppresses the medullary rhythmicity center and may result in death.

Herpes Zoster (Shingles)
Occasionally herpesvirus infects a dorsal root ganglion. This causes severe pain in the dermatomal segment subserved by the ganglion, thus eliciting a segmental type of pain that circles halfway around the body. The disease is called herpes zoster, or "shingles," because of a skin eruption that often ensues. The cause of the pain is presumably infection of the pain neuronal cells in the dorsal root ganglion by the virus. In addition to causing pain, the virus is carried by neuronal cytoplasmic flow outward through the neuronal peripheral axons to their cutaneous origins. Here the virus causes a rash that vesiculates within a few days and then crusts over within another few days, all of this occurring within the dermatomal area served by the infected dorsal root.

Tic Douloureux
Lancinating pain occasionally occurs in some people over one side of the face in the sensory distribution area (or part of the area) of the fifth or ninth nerves; this phenomenon is called tic douloureux (or trigeminal neuralgia or glossopharyngeal neuralgia). The pain feels like sudden electrical shocks, and it may appear for only a few seconds at a time or may be almost continuous. Often it is set off by exceedingly sensitive trigger areas on the surface of the face, in the mouth, or inside the throat-almost always by a mechanoreceptive stimulus rather than a pain stimulus. For instance, when the patient swallows a bolus of food, as the food touches a tonsil, it might set off a severe lancinating pain in the mandibular portion of the fifth nerve.
The pain of tic douloureux can usually be blocked by surgically cutting the peripheral nerve from the hypersensitive area. The sensory portion of the fifth nerve is often sectioned immediately inside the cranium, where the motor and sensory roots of the fifth nerve separate from each other, so that the motor portions, which are necessary for many jaw movements, can be spared while the sensory elements are destroyed. This operation leaves the side of the face anesthetic, which in itself may be annoying. Furthermore, sometimes the operation is unsuccessful, indicating that the lesion that causes the pain might be in the sensory nucleus in the brain stem and not in the peripheral nerves.

Brown-Séquard Syndrome
If the spinal cord is transected entirely, all sensations and motor functions distal to the segment of transection are blocked, but if the spinal cord is transected on only one side, the Brown-Séquard syndrome occurs. All motor functions are blocked on the side of the transection in all segments below the level of the transection. Yet only some of the modalities of sensation are lost on the transected side, and others are lost on the opposite side. The sensations of pain, heat, and cold-sensations served by the spinothalamic pathway-are lost on the opposite side of the body in all dermatomes two to six segments below the level of the transection. By contrast, the sensations that are transmitted only in the dorsal and dorsolateral columns-kinesthetic and position sensations, vibration sensation, discrete localization, and two-point discrimination-are lost on the side of the transection in all dermatomes below the level of the transection. Discrete "light touch" is impaired on the side of the transection because the principal pathway for the transmission of light touch, the dorsal column, is transected. That is, the fibers in this column do not cross to the opposite side until they reach the medulla of the brain. "Crude touch," which is poorly localized, still persists because of partial transmission in the opposite spinothalamic tract.

Spinal Cord Reflexes That Cause Muscle Spasm

In human beings, local muscle spasm is often observed. In many, if not most, instances, localized pain is the cause of the local spasm.

Muscle Spasm Resulting from a Broken Bone
One type of clinically important spasm occurs in muscles that surround a broken bone. The spasm results from pain impulses initiated from the broken edges of the bone, which cause the muscles that surround the area to contract tonically. Pain relief obtained by injecting a local anesthetic at the broken edges of the bone relieves the spasm; a deep general anesthetic of the entire body, such as ether anesthesia, also relieves the spasm. One of these two anesthetic procedures is often necessary before the spasm can be overcome sufficiently for the two ends of the bone to be set back into their appropriate positions.

Abdominal Muscle Spasm in Peritonitis
Another type of local spasm caused by cord reflexes is abdominal spasm resulting from irritation of the parietal peritoneum by peritonitis. Here again, relief of the pain caused by the peritonitis allows the spastic muscle to relax. The same type of spasm often occurs during surgical operations; for instance, during abdominal operations, pain impulses from the parietal peritoneum often cause the abdominal muscles to contract extensively, sometimes extruding the intestines through the surgical wound. For this reason, deep anesthesia is usually required for intra-abdominal operations.

Muscle Cramps
Still another type of local spasm is the typical muscle cramp. Electromyographic studies indicate that the cause of at least some muscle cramps is as follows: Any local irritating factor or metabolic abnormality of a muscle, such as severe cold, lack of blood flow, or overexercise, can elicit pain or other sensory signals transmitted from the muscle to the spinal cord, which in turn cause reflex feedback muscle contraction. The contraction is believed to stimulate the same sensory receptors even more, which causes the spinal cord to increase the intensity of contraction. Thus, positive feedback develops, so a small amount of initial irritation causes more and more contraction until a full-blown muscle cramp ensues.

Functions of Brain Stem Nuclei in Controlling Subconscious, Stereotyped Movements
Rarely, a baby is born without brain structures above the mesencephalic region, a condition called anencephaly. Some of these babies have been kept alive for many months. They are able to perform some stereotyped movements for feeding, such as suckling, extrusion of unpleasant food from the mouth, and moving the hands to the mouth to suck the fingers. In addition, they can yawn and stretch. They can cry and can follow objects with movements of the eyes and head. Also, placing pressure on the upper anterior parts of their legs causes them to pull to the sitting position. It is clear that many of the stereotyped motor functions of the human being are integrated in the brain stem.

Engrams: The stored of mental sequence of motor act called engram or you can call it ready-made programs. Examples of such engrams are tying shoe laces, writing a letters of alphabet, cutting paper with scissors, hammering nails, shooting basketball through a hoop, passing a football, throwing a baseball, the movements of shoveling dirt, movements of the fingers during typing or playing piano. There are two types of such ready-made programs:

[A] Sensory engram: In which the sequential pattern of movement of learned slow and complex motor activities are stored in the somatic sensory areas. Then the person can use this sensory engram as a guide for the motor system of the brain to follow in reproducing the same pattern of movement. Examples of sensory engrams are tying shoe laces, writing a letters of alphabet, cutting paper with scissors, hammering nails, shooting basketball through a hoop, passing a football, throwing a baseball, the movements of shoveling dirt. Somatic sensory areas send these engram to premotor cortex and then to primary motor cortex to be executed as motor act. The motor activity dictated by the sensory engram is checked by feedback signals from peripheral sensory receptors to sensory cortex to correct any error if the peripheral sensory signals do not match with the sensory engram. The somatic sensory area and related portions are providing fibers that run in the corticospinal and corticobulbar tracts, and to the premotor area. Therefore, lesions of the somatic sensory area cause defect in motor performance that are characterized by inability to execute learned sequences of movements such as eating with a knife and fork.

[B] Motor engram: In which the sequential pattern of movement of learned rapid and complex motor activities is stored in the premotor cortex as well as in the sensory cortex. Examples of such engrams are the movements of the fingers during typing or playing piano. Many motor activities are performed so rapidly that there is insufficient time for sensory feedback signals to control these activities. For instance, the movements of the fingers during typing occur much too rapidly for somatic sensory signals to be transmitted to the somatic sensory cortex or even to directly to motor cortex and for these then to control each discrete movement. The motor activities dictated by the motor engram can occur entirely without sensory feedback control. However, the sensory system still determines whether or not the act has been performed correctly. This is achieved after the act has been performed and helps in correction the act in the next time it is performed. It is believed that the control of these rapid coordinate muscular movements involves primary motor and premotor cortex, basal ganglia, and cerebellum.

You may have many ready-made programs for the same goals of a motor acts, such as tying shoe laces while you are in standing position with no chair available, or tying your shoe lace by raising your foot, etc. You can then perform the movement smoothly and easily by triggering the pattern rather than by controlling the individual neurons. This principle applies to any learned movement, from something as simple as picking up a glass to something as complex as playing the piano. There is a reason to believe that hundreds of learned different patterns of movements (ready-made programs, or motor engram) are stored in the premotor cortex, which in combination can produce thousands to millions movements which could allow almost any type of motor activity.

When a movement, as dictated from specific engram, due to occur, then the premotor cortex, under instructions from the supplementary motor area transmits instructions to the specific primary motor areas which in turn activate specific motor units for the intended movement. To achieve a motor act, the premotor area sends its signals into the primary motor cortex to excite multiple groups of muscle either directly or indirectly (through basal ganglia è thalamus è primary and premotor motor cortex). Basal ganglia in association with cerebellum play important role in planning, programming and timing of the learned complex pattern of motor activity (engram) and in deciding which specific engram should be executed.

Thalamic Syndrome

Thrombosis of the posterolateral branch of the posterior cerebral artery may sometimes produce ischaemic damage of posteroventral thalamus. The lesion manifests as impairment of discrimination in sensory perception, hypotonia, muscular
weakness and incoordination, and volatile emotions, pleasant or unpleasant. After a few weeks to months, partial recovery may occur. But the sensations, regardless of the nature of the stimulus, may be very painful. The symptoms are thought to arise partly because the medial nuclei of the thalamus are spared by the lesion. The medial nuclei are the nonspecific nuclei which receive major projections from pain fibres. Hence
the dominance of pain among the sensations. The symptom complex is called thalamic syndrome.

Dead, or Not Yet?

It has been said that nothing is certain except death and taxes. Doctors have traditionally declared a person dead when his heart beat and respiration have stopped. But recent advances in technology have made it uncertain whether the traditional criteria are essential for certifying death. A person’s respiration and circulation may be maintained artificially for long periods of time even after the person is dead for all practical purposes. Is the time, effort and expense involved in keeping such a person ‘alive’ justified? Can such a person’s organs be removed for transplantation? An answer to these difficult ethical and legal questions has been provided by EEG. EEG silence, or brain death, is now an accepted criterion of death. However, in order to prevent misuse of this criterion, strict guidelines have been suggested for diagnosing cerebral death. Broadly, these guidelines require that all necessary diagnostic and therapeutic procedures should have been performed on the patient. Further, the patient should have been in coma and apnoea for at least 6 h, following which EEG silence should have been present continuously for at least 30 min. EEG silence is defined as absence of electrical potentials over 2 microvolts from symmetrically placed electrode pairs over 10 cm apart and with an interelectrode resistance between 100 and 10000 ohms.

NOTES: Cerebral lateralization, or dominance, seems to be stronger in men than in women. In fact, when the left hemisphere
is damaged, men are three times as likely to suffer aphasia. Although the reason for this isn’t completely clear, scientists speculate that women have more communication between their right and left hemispheres.

Control of equilibrium (or postural reflexes)

Reflex Arc of Postural Reflex:

Afferent Pathway- comes from the muscle spindles and Golgi tendon organ, eyes, the vestibular apparatus, the pressure receptors and proprioceptors.
Integrating Centers- are formed by neuronal network in the brain stem and spinal cord.
Efferent Pathway- α-motor neurons supplying the various skeletal muscles i.e. the effector organ.

Functions of postural reflexs:
1. To support head and body against gravity through antigravity (static) reflexes. These reflexes maintain the body in an upright balanced position against the gravity. This is achieved by controlling the muscles tone (Stretch reflex) of antigravity muscles.

2. To align the body with center of gravity (static) to maintain center of body’s mass over center of support. These reflexes are:

Crossed extensor reflex.
Long loop stretch reflexes (functional stretch reflexes): In which the central integration is the cortex. These reflexes are continuously active in erect posture. They bring about continuous correction of the sways that occur from moment to moment during standing. These are polysynaptic reflexes; the stimulus for it is stretch of muscles due to sways which occur during standing. The receptors are muscle spindles and the centers of the reflex arcs are in the cerebral cortex.
Body pressure receptors: Differential stimulation of the pressure receptors in the body wall: This will reflexly right the head. Pressure signals from the footpads to apprise the CNS whether weight is distributed equally between the two feet or whether weight is more forward or backward on the feet. The same thing can apply for the pressure receptors over various parts of the body. An example of it is the movement against winds in which the air pressure against the front of the body signals that a force is opposing the body in a direction different from that caused by gravitational pull, as a result, the person leans forward to oppose this.
Postural labyrinthine tonic reflex (tonic postural vestibular reflexes): This reflex is produced in response to alteration of the position of the head relative to the horizontal plane, e.g. while standing on an inclined plane. The stimulus for the tonic labyrinthine reflexes is gravity, the receptors are the otolith organs, and the afferents for the tonic labyrinthine reflexes travel along vestibular nerve, the centers of these reflexes are vestibular and reticular nuclei. The efferents travel in the vestibulospinal and reticulospinal tracts to the motor neurons in the spinal cord. Reflex response is there is extension of the limbs in the direction of downward tilt and retraction of the others.

3. To provide a stable background for movement (dynamic or phasic) and to stabilize supporting parts of body while other parts move. These reflexes maintain the body in balance during the movement of the body. The mechanism, which maintains balance during voluntary action, forms the phasic postural reflex.

Tonic neck reflex: These reflexes are produced in response to alternation in the position of head relative to the body. The stimulus of this reflex is stretch of neck muscles (due to stimulation of proprioceptors receptors in the ligaments of the cervical joint and muscle spindle of neck muscles). The integration of such reflex is in the medulla oblongata. The efferents are the corticospinal tracts. Signals from the joint proprioceptors especially of the neck to the vestibular nuclei and the reticular formation, apprises the NS about the orientation of the head with respect to the body for the maintenance of equilibrium. For instance, when the head is leaned in one direction by bending the neck, impulses from the neck proprioceptors keep the vestibular apparatuses from giving the person a sense of malequilibrium. They do this by transmitting signals that exactly oppose the signals transmitted from the vestibular apparatuses. However, when the entire body leans in one direction, the impulses from the vestibular apparatuses are not opposed by the neck proprioceptors therefore, the person in this instance does perceive a change in equilibrium status. The vestibular receptors inform about the position and movements of the head in space, whereas neck proprioceptors can inform about the position and movements of the body in relation to the head. On the basis of information from both kinds of receptors, the brain can decide whether the head is moving in isolation or whether it moves together with the rest of the body. Generally speaking, the labyrinthine reflexes when operating alone produce muscle contractions in the trunk and extremities that serve to keep the position of the head constant. The neck reflexes, as mentioned, serve to keep the position of the body constant in relation to the head. The latter is a prerequisite for the labyrinthine reflexes to function properly; the vestibular apparatus can provide information only about the position of the head in space and not about its position in relation to the body. Thus, the labyrinthine reflexes work on the assumption that the head has a constant position relative to the body, and the neck reflexes ensure that this position is constant.
Postural labyrinthine righting reflex (Head righting reflex): It is a reflex that corrects the orientation of the head when it is taken out of its normal upright position (as detected by otolith organs). It is initiated by the vestibular system, which detects that the head is not erect and causes the head to move back into position as the rest of the body follows. The perception of head movement involves the body sensing linear acceleration or the force of gravity through the otoliths, and angular acceleration through the semicircular canals. The reflex uses a combination of visual system inputs, vestibular inputs, and somatosensory inputs to make postural adjustments when the body becomes displaced from its normal vertical position. These inputs are used to create what is called an efference copy by the cerebellum. This means that the brain makes comparisons in the cerebellum between expected posture and perceived posture, and corrects for the difference. If the head is forcibly tilted in different directions, so that the head righting reflexes cannot operate, one can also observe compensatory static vestibulo-ocular reflexes that similarly help to maintain the normal attitude of the eyes with respect to the outside world. Many persons with complete destruction of the vestibular apparatus have almost normal equilibrium as long as their eyes are open and as long as they perform all motions slowly. But, when moving rapidly or when the eyes are closed, equilibrium is immediately lost.
Optical righting reflexes: Optical impulses also cause righting of the head in animals with intact visual cortex.

The functions of amygdala:

Amygdala has extensive connections with various parts of the brain.
It plays its important role on the:

Mediation and control of major affective activities like friendship, love and affection, on the expression of mood and, mainly, on fear, rage, placidity and aggression.

The amygdala, being the center for identification of danger, is fundamental for self-preservation. When a situation is perceived as threatening, the sensation of anxiety and fear together with activation of the stress response is experienced in which the sympathetic nervous system and the hypothalamic-pituitary-adrenal hormone axis are stimulated. Lesions in this area can prevent fear. Higher cortical areas integrate sensory information with learned experience and produce descending input to the amygdala, which results in the sensation of fear. Output from the amygdala to the hypothalamus results in activation of the “fight or flight” response by the sympathetic nervous system.
The amygdala is believed to help in choosing the pattern of the person’s behavioral response so that it is appropriate for each occasion.
The amygdala also seems to be involved in a broad range of functions including food intake, sexual activity.
The amygdala helps to store memories of events and emotions so that an individual may be able to recognize similar events in the future. For example, if you have ever suffered a dog bite, then the amygdalae may help in processing that event and, therefore, increase your fear or alertness around dogs.
The amygdala in humans also plays a role in sexual activity and libido, or sex drive. It can change in size and shape based on the age, hormonal activity, and gender of the individual. For example, males who have low testosterone, or who may have been castrated, (had their testicles removed), tend to have smaller amygdalae, and, in turn, may also have a lower sex drive.

The hippocampus has a calming effect on activation of the stress response, and provides a negative feedback pathway to limit the stress response. This is occurred probably through the following mechanisms:

Increased plasma concentration of cortisol is part of the stress response.
Cortisol stimulates areas of the hippocampus.
The hippocampus inhibits activation of the stress response by the hypothalamus. When a person experiences chronic stress, the negative feedback mechanism appears to be less effective due to persistently high levels of cortisol and resulting damage or down regulation of the hippocampus.

Bilateral lesions in the amygdala cause hyperphagia with indiscriminate ingestion of all kinds of food (omniphagia), loss of fear, decrease aggressiveness, tameness, and excessive sex drive, psychic blindness, has extreme curiosity about everything, forgets very rapidly, has a tendency to place everything in its mouth. Aggression is an emotion related to fear, and is also mediated
by the amygdala and hypothalamus. The size of the amygdala is positively correlated with increased aggression and physical behavior. Surgical or laboratory induced lesions in the amygdala can result in both a flattening of emotions and loss of fear and also produce a placid state. Aggression is normally suppressed by higher parts of the limbic system in the frontal cortex, which, if severed, may result in
uncontrolled rage.

The functions of hippocampus:

1. Hippocampus works as a filter. Perhaps only 1 per thousand of all received signals contain useful information and are stored in the memory. The easiest facts to remember are those that make sense.
2. Hippocampus is the "brain librarian", i.e. helps the cortex to store new signals into the long lasting long-term memory. Bilateral removal of the hippocampi permanently disrupts the ability to learn anything new (anterograde amnesia). Other lesions of the hippocampi reduce previously learned memory material (retrograde amnesia). All facts, concepts and acquired skills are stored in a ready-to-use fashion. Stimulation of different areas in the hippocampus can cause almost any one of different behavioral patterns, such as rage, passivity, excess sex drive, etc. Such emotions play a large role in memory, and strong impressions that are charged with emotion engrave themselves into our memory. The hippocampus has extensive connections with most portions of the cerebral cortex as well as with the basic structures of the limbic system. The hippocampus is particularly vulnerable to several disease processes, including ischemia, which is any obstruction of blood flow or oxygen deprivation, Alzheimer's disease, and epilepsy.
3. The hippocampus has also been found to have a huge impact in learning.

Functions of specific chemical transmitter system for behavior control:

1. The epinephrine-serotonin system: Large numbers of norepinephrine- secreting neurons are located in the reticular formation especially in the locus ceruleus which sends fibers upward to most parts of the limbic system, thalamus, and cerebral cortex. Also, many serotonins-producing neurons are located in the midline raphe nuclei of the lower pons and medulla and also project fibers to many areas of the limbic system and to some areas of the brain.

Mental depression psychosis might be caused by diminished formation of either norepinephrine or serotonin or both. This suggestion is supported by finding that the drugs that block the secretion of norepinephrine or serotonin cause depression and the drugs that increase norepinephrine and serotonin at the nerve endings can treat about 70% of patients with depression. In addition, some patients with mental depression alternate between depression and mania (manic-depressive psychosis) can be treated with drugs that block the formation or action of norepinephrine and serotonin during the manic condition.

2. The dopamine system: The dopaminergic neurons are located in the substantia nigra and ventral tegmentum. The dopaminergic neurons located in substantia nigra project inhibitory effects on the basal ganglia. The dopaminergic neurons of tegmentum project fibers to the limbic system via mesolimbic dopaminergic system. Schizophrenia might be caused by excess secretion of dopamine in the brain. This suggestion is supported by finding that drugs that cause excess release of dopamine in the brain may cause schizophrenic symptoms and the drugs that decrease the secretion of dopamine by the dopaminergic nerve endings or decrease the effect of dopamine on subsequent neurons can treat patients with schizophrenia.

Speech defects:

Speech defects are divided into two main categories"
(I) Aphasia
Speech defects: Speech defects are divided into two main categories"
(I) Aphasia
1. Sensory (receptive) aphasia.
2. Motor aphasia.
3. Wernicke's aphasia.
4. Global aphasia.
(II) Dysarthria: It is a speech defect in a patient who can see, hear and move the muscles of speech.

1. Sensory (receptive) aphasia: Sensory aphasia is found in two forms:
(a) Sensory auditory aphasia (word deafness): This is due to a lesion in the auditory interpretative area. The patient can hear the spoken words, but is unable to understand the message.
(b) Sensory visual aphasia (word blindness or dyslexia): This is due to a
lesion in the visual interpretative area. The patient can see the written words but is unable to understand the message.

2. Motor (expressive) aphasia: Motor aphasia is found in two forms:
(a) Vocal aphasia: This is due to a lesion in Broca's area. The Patient is perfectly capable of deciding what he wishes to say and is capable of vocalization, but he simply cannot make his vocal system emit words, but only noises (nonfluent aphasia). Patients with lesion of Broca's area (in the dominant hemisphere) frequently suffer from paralysis of the opposite side (right) of the body. An exmple of Broca`s aphasia: “Ah ... Monday ... ah Dad and Paul [patient’s name] ... and Dad ... hospital. Two ... ah doctors ..., and ah ... thirty minutes ... and yes ... ah ... hospital. And, er Wednesday ... nine o’clock. And er Thursday, ten o’clock ... doctors. Two doctors ... and ah ... teeth. Yeah, ..., fine.
(b) Writing aphasia (agraphia): This is one to a lesion in the hand skill area. The patient knows what he wants to writs or draw and he is capable of moving the hand voluntarily, but he cannot make his hands write words or draw graphs to express his thoughts.''

3. Wernicke's aphasia: This aphasia is caused by lesions in Wernicke's area of the categorical hemisphere. The patient comprehends ideas expressed by spoken or written words. He formulates thoughts and ideas but doesn't know how to express them. The process of verbalization is normal, so the patient can talk and sometimes he talks too much (fluent aphasia). However, his speech is full of jargon (speech full of too much unnecessary words) and neologism (new words invented by the patient) that make little sense. Very rarely, when the lesion is in the arcuate fasciculus, the Wernicke's, area is disconnected from Broca's area. The patient knows what he wants to say, but cannot produce the required speech. This condition is called "conduction aphasia".

4. Global aphasia: This aphasia is caused by extensive lesions in the categorical hemisphere involving both frontal and temporal lobes. The aphasia is general; it involves the receptive and expressive functions.

[II] Dysarthria: Dysarthria means difficulty in producing clear, normal speech due to a defect in the motor system of verbalization. There is either weakness, incoordination, hyper or hypotonia, or paralysis of the muscles of speech.

disorders of sleep

Disorders of sleep are divided into two major categories and these are:
[1] Narcolepsy: This is inappropriate attack of irresistible desire to sleep. Individuals with this disorder suddenly fall asleep without regard for the time of day, location, or the activity in which they are engaged. Lesions in the hypothalamus may produce narcolepsy. Sleep lasts for short periods could be only few minutes of which the patient wakes up fully recovered. Narcolepsy can have any of the following four characteristics:

Sleep attacks which are brief, and can occur at any time without any warning.
Cataplexy is a complete loss of muscle tone that frequently occurs following emotional excitement while the subject is awake.
Sleep paralysis occurs when a person in bed and is ready to fall asleep and during it the subject can be aroused by external stimuli such as touch or sound.
Auditory and visual hallucination which occur during sleep paralysis as the subject is falling asleep (hypnagogic hallucination) and it may occurs while the subject is waking up (hypnopompic hallucination).

[2] Insomnia: Inability to obtain the amount and quality of sleep required to maintain normal function. Insomnia can results from irritative lesions in the hypothalamus. There are four major causes of insomnia [a] disturbances in the circadian rhythm [b] emotional disturbances [c] anticipation of not being able to sleep, and [d] restless leg syndrome (which is a condition in which patients have the urge to keep their leg in motion before falling asleep.
Drugs like barbiturates were used frequently for the treatment of insomnia by increasing the sleeping time but they reduce the duration of stage 3 and 4 of slow-wave sleep and REM sleeping time. Therefore, treatment with barbiturates reduces the quality of sleep. The drugs like benzodiazepines (e.g., valium) and increasing age decrease the duration of REM sleep and stage 4 of slow-wave sleep. REM sleep decrease with age, and wake periods occur in increasing number. This is why elderly people believe that they do not sleep sufficiently.

Evoked Potentials:

When a sensory pathway is stimulated the electrical changes which take place in part of the pathway can be picked up in recordings made from the surface of the scalp. These electrical changes are called evoked potentials. Evoked potentials are broadly of two types. The first type of evoked potentials have a short latency (less than 100 ms). Some of these originate in the brainstem, some in the thalamus, and the rest in the cerebral cortex. Their presence indicates that the sensory pathway is intact. The second type of evoked potentials have a long latency (100-1000 ms) and are called event related potentials (ERP). ERP provide information about cortical processing. ERP appear in electroencephalographic recordings as a series of negative (N1, N2 …) and positive (P1 , P2 …) waves. By convention, the upward deflections are termed negative, the downward deflections positive. The most frequently used experimental situation in the study of ERP is the oddball paradigm. In this paradigm frequent stimuli (80%) are randomly mixed with rare stimuli (20%), and the subject is required to count the rare stimuli. The rare stimulus results in a large positive parietal wave with a latency of about 300 ms, and therefore called P 300. Evoked potentials may be used for assessing the prognosis of a patient in coma (i.e. a patient who is unconscious, and cannot be aroused even by painful stimuli). In such a patient, if evoked potentials with a latency of less than 50 ms are absent, the patient usually does not survive. This is understandable because short latency responses correspond to processing in the brainstem and thalamus. If even these structures are not functioning, chances of recovery are bleak. On the other hand, if ERP are present, the outcome is usually good. That is also understandable because ERP correspond to cortical processing. If even the cortical processing is going on, it means that the damage is minimal and reversible. About 30-50% of comatose patients have P 300 present. This raises the possibility that if they show a cortical electrophysiological response to the oddball paradigm or some such feature of the stimulus, they may be more aware than they seem. Possibly the sensorium is not as disturbed as the capacity for motor response to the sensory stimulus. This is in keeping with the anecdotes of patients recounting what was going on while they were in coma after they recover consciousness. Therefore one should be careful not to say anything unkind near the patient even if the patient is in coma.

Alzheimer disease (AD) is a disorder characterized by a gradual loss of reason that begins with memory lapses and ends with the inability to perform any type of daily activity. Personality changes signal the onset of AD. A normal 50- to 60-year-old might forget the name of a friend not seen for years. People with AD, however, forget the name of a neighbor who visits daily. People afflicted with AD become confused and tend to repeat the same question. Signs of mental disturbance eventually appear, and patients gradually become bedridden and die of a complication, such as pneumonia. Researchers have discovered that in some families whose members have a 50% chance of AD, a genetic defect exists on chromosome 21. This is of extreme interest because Down syndrome, as you know, results from the inheritance of three copies of chromosome 21, and people with Down syndrome tend to develop AD. AD is characterized by the presence of abnormally structured neurons and a reduced amount of ACh. The AD neuron has two features: (1) Bundles of fibrous protein, called neurofibrillary tangles, surround the nucleus in the cells, and (2) Protein-rich accumulations, called amyloid plaques, envelop the axon branches. These abnormal neurons are especially seen in the portions of the brain involved in reason and memory. Drugs that enhance acetylcholine production are currently being tested in AD patients. Experimental drugs that prevent neuron degeneration are also being tested. For example, it is possible that nerve growth factor, a substance that is made by the body and that promotes the growth of neurons, will one day be tested in AD patients.

Drug abuse

is the chronic self-administration of a drug in doses high enough to cause addiction—a physical or psychological dependence in which the user is preoccupied with locating and taking the drug. Stopping drug use causes intense, unpleasant withdrawal symptoms. Prolonged and repeated abuse of a drug may also result in drug tolerance, in which the physiological response to a particular dose of the drug becomes less intense over time. Drug tolerance results as the drug increases synthesis of certain liver enzymes, which metabolize the drug more rapidly, so that the addict needs the next dose sooner. Drug tolerance also arises from physiological changes that lessen the drug’s eﬀect on its target cells. The most commonly abused drugs are CNS depressants (“downers”), CNS stimulants (“uppers”), hallucinogens, and anabolic steroids.

CNS depressants include barbiturates, benzodiazepines, opiates, and cannabinoids. Barbiturates act uniformly throughout the brain, but the reticular formation is particularly sensitive to their eﬀects. CNS depression occurs due to inhibited secretion of certain excitatory and inhibitory neurotransmitters. Eﬀects range from mild calming of the nervous system (sedation) to sleep, loss of sensory sensations (anesthesia), respiratory distress, cardiovascular collapse, and death. The benzodiazepines, such as diazepam, depress activity in the limbic system and the reticular formation. Low doses relieve anxiety, and higher doses cause sedation, sleep, or anesthesia. These drugs increase either the activity or release of the inhibitory neurotransmitter GABA. When benzodiazepines are metabolized, they may form other biochemicals that have depressing eﬀects. The opiates include heroin (which has no legal use in the United States), codeine, morphine, meperidine, and methadone. These drugs stimulate certain receptors (opioid receptors) in the CNS, and when taken in prescribed dosages, they sedate and relieve pain (analgesia). Opiates cause both physical and psychological dependence. Eﬀects of overdose include a feeling of well-being (euphoria), respiratory distress, convulsions, coma, and possible death. On the other hand, these drugs are very important in treating chronic, severe pain. For example, cancer patients find pain relief with oxycodone, which is taken twice daily in a timed-release pill. The cannabinoids include marijuana and hashish, both derived from the hemp plant. Hashish is several times more potent than marijuana. These drugs depress higher brain centers and release lower brain centers from the normal inhibitory influence of the higher centers. This induces an anxiety-free state, characterized by euphoria and a distorted perception of time and space. Hallucinations (sensory perceptions that have no external stimuli), respiratory distress, and vasomotor depression may occur with higher doses.

CNS stimulants include amphetamines and cocaine (including “crack”). These drugs have great abuse potential and may quickly produce psychological dependence. Cocaine, especially when smoked or inhaled, produces euphoria but may also change personality, cause seizures, and constrict certain blood vessels, leading to sudden death from stroke or cardiac arrhythmia. Cocaine’s very rapid eﬀect, and perhaps its addictiveness, reﬂect its rapid entry and metabolism in the brain. Cocaine arrives at the basal nuclei in four to six minutes and is mostly cleared within thirty minutes. The drug inhibits transporter molecules that remove dopamine from synapses after it is released. “Ecstasy” is a type of amphetamine.

Hallucinogens alter perceptions. They cause illusions, which are distortions of vision, hearing, taste, touch, and smell; synesthesia, such as “hearing” colors or “feeling” sounds; and hallucinations. The most commonly abused and most potent hallucinogen is lysergic acid diethylamide (LSD). LSD may act as an excitatory neurotransmitter. Persons under the influence of LSD may greatly overestimate their physical capabilities, such as believing they can ﬂy oﬀ the top of a high building. Phencyclidine (PCP) is another abused hallucinogen. Its use can lead to prolonged psychosis that may provoke assault, murder, and suicide.