CNS Physiology PDF

Mustansiriyah College of Medicine The Central Nervous System Physiology 1 Mustansiriyah College of Medicine Nervous System Functions:. Coordinate the activities of other systems (along with the endocrine system) through senses and responses to internal and external events; therefore, it maintains homeostasis of the body. This is achieved via the sensory and motor functions of the CNS.. Store experiences (memory) and establishes patterns of response based on prior experiences (learning). The functional levels of CNS: The intercommunication between the external environment and the CNS is mediated by the sensory-somatic peripheral nervous system, while the intercommunication between the internal environment and the CNS is mediated by autonomic peripheral nervous system. The CNS can be divided into three functional levels: 1- Spinal cord level: Spinal cord acts (a) as a conduit for signals from the periphery of the body to the brain or in opposite direction from the brain back to the body. In addition to this function (b) many reflex control centers are located in the spinal cord, which are in turn controlled by higher levels of CNS. 2- The lower brain level (subcortical level): Most of the subconscious activities of the body are controlled in the lower areas of the brain, i.e. medulla, pons, epencephalon, hypothalamus, thalamus, cerebellum, basal ganglia. Such of these activities are control of arterial pressure, respiration, control of equilibrium, feeding reflexes, many emotional patterns such as anger, excitement, sexual activities, reaction to pain, reaction to pleasure. 3- The higher brain level (cortical level): Cerebral cortex converts the lower CNS function into very determinative precise operations. In addition, the cerebral cortex is a very large memory storehouse and it is essential for most of our thought processes in association with the lower CNS centers. The neuronal pools: Neuronal pool (or nuclei or centers) is a collection of intercommunicated neurons. Each pool has its own special characteristics of organization which 2 Mustansiriyah College of Medicine cause it to process signals in its own special way. The examples of such pools are basal ganglia, specific nuclei in the thalamus, and cerebellum etc. The CNS is made up of thousands of separate neuronal pools. Each pool has fiber tracts coming to it (afferent fibers) and other leaving it (efferent fibers). The input signals to the neuronal pool may excite, inhibit, or facilitate the neurons within the pool. The neuronal pool may allow the incoming signals to pass sequentially (serial processing), to allow the same incoming signal to pass simultaneously (parallel processing), or amplifies the input signal (amplification) and transmit these amplified signals to one or different directions (divergence). Sometimes an incoming signal to a neuronal pool causes an output excitatory signal going in one direction and at the same time an inhibitory signal going elsewhere. The center may summate the effects of multiple incoming signals that converge on the same pool (convergence). And, sometimes a signal entering a pool causes a prolonged output discharge (called after-discharge), even after the incoming signal is over. The mechanisms by which after - discharge occurs are the following: [a] Synaptic after-discharge: When excitatory synapses discharge on the surface of postsynaptic neuron a long-acting synaptic transmitter substances. [b] Parallel circuit for after- discharge: When the input signal spreads through a series of neurons in the neuronal pool and from many of these neurons impulses keep converging on an output neuron. [c] Reverberatory circuit for after- discharge: When excitatory signal stimulate a neuron in a neuronal pool, the excited neuron in the pool feeds back to re-excite itself. Examples of reverberatory system are those which occur during respiration in which the inspiratory neuronal pool in the medulla become excited for about 2 sec during each respiratory cycle. Also one theory of wakefulness is that continual reverberation occurs somewhere within the brain stem to keep a wakefulness area excited during the waking hours. Some neuronal pools emit output signals continuously even without excitatory input signals. This occurs probably due to the rhythmical property of the neurons within the pool or due to the reverberating circuits. Stabilization of neuronal circuits by inhibitory mechanisms: Without the stabilization of the neuronal circuits of the brain, any excitatory signal entering any part of the brain would set off a continuous cycle of re-excitation of all other parts and therefore, the brain would be busy by a mass of uncontrolled signals that would be transmitting no information. Such an effect actually occurs in widespread areas of the brain during epileptic convulsions. The NS prevents this from happening all the time by inhibiting the signal transmission. Some neuronal pools exert gross inhibitory control over widespread areas of the brain such as many of the basal ganglia which exert inhibitory influences throughout the motor control system. Physiologically, the inhibitory mechanisms within the CNS are of two types: (1) Presynaptic inhibitory mechanism: In which the inhibition occur at the presynaptic neuron before the signal reaches the synapse itself. Presynaptic inhibition can be achieved by two different mechanisms: (A) Opening Cl and K ion channels at the presynaptic terminal: In which an inhibitory neuron 3 Mustansiriyah College of Medicine synapses an adjacent neuron at its axon or terminals and secretes an inhibitory transmitter substance (mostly GABA) which opens Cl and K ion channels at the axon or the terminal of the presynaptic neuron. The opening of Cl and K channels allows Cl ions to diffuse into the terminal fibril and K ions to diffuse out of the terminal fibril (causing a state of local hyperpolarization) and cancel much of the excitatory effect of the positively charged Na ions that enter the terminal fibril when an action potential arrives. Consequently, this will lead to reduce the voltage of the action potential that reaches the synaptic membrane of the terminal. And consequently decreases the amount of Ca ions that enter the terminal and therefore also the amount of transmitter released by the terminal. Therefore, the degree of excitation of the postsynaptic neuron is greatly suppressed or inhibited. (B) Blocking Ca channels: Some of the inhibitory neurons secrete an inhibitory neurotransmitter (such as enkephalin) at the membrane of the terminal buttons of the presynaptic neurons that block Ca channels in the membrane of the nerve terminal and consequently decreases the amount of Ca ions that enter the terminal and therefore also the amount of transmitter released by the terminal. (2) Postsynaptic inhibitory mechanism: This type of inhibition can be due to the generation of IPSP at the postsynaptic membrane or the occurrence of the synaptic fatigue in which the signal becomes progressively weaker with the more prolonged period of excitation. Other form of synaptic inhibition is the presence of refractory period at the postsynaptic neuron. Anatomically, the inhibition of an informational pathway within the CNS can occurred at two different locations and these are: [I] Lateral inhibition: In which the nerve fibers of a pathway give off collateral fibers that synapse with an inhibitory neuron. The inhibitory interneuron then send its nerve fiber to synapse at the axon or the terminal of the adjacent less excited neurons in the signal pathway preventing signals in an informational pathway from spreading diffusely everywhere. [II] Recurrent inhibition (inhibitory feedback circuits): In which a collateral terminal return from the pathway back to excite an inhibitory interneuron which in turn send its fiber to the initial excitatory neuron of the same pathway and lead to inhibition of it. Adjustment of the pathway sensitivity: The nervous system can adjust the sensitivity of an informational pathway by two mechanisms: 1- The fatigue mechanism for automatic short-term adjustment: In which the overused pathways usually become fatigue so that their sensitivities will reduced. On the other hand, those that are underused will become rested and their sensitivities will increase. 2- Downgrading or upgrading of synaptic receptors for automatic long-term adjustment: In which over usage of a circuit will lead to gradually decreasing sensitivity of the synapses because of decreased receptor proteins (downgrading), while under usage will cause increase in sensitivity because of increased receptor proteins (upgrading). 4 Mustansiriyah College of Medicine Somatosensory functions of the CNS Sensory receptors and their basic mechanisms of action Somatosensory system is defined as the sensory system associated with different parts of the body. Input to the NS is provided by the sensory receptors that detect sensory stimuli. Sensory receptors are specialized cells or neurons that transduce environmental signals (mechanical forces, light, sound, chemicals, and temperature) into neural signals (action potential) in neuron attached to it. According to the type of energy or stimulus that stimulates receptors, there are five different types of sensory receptors: Mechanoreceptors, which detect mechanical deformation of the receptor or of cells adjacent to the receptor which include tactile sensations (touch, pressure, vibration, tickles, itch, stereognosis), hearing, equilibrium, and the position sense (or proprioceptive). Proprioceptors monitor the position of joints, the tension in tendons and ligaments, and the state of muscular contraction. There are three major groups of proprioceptors: Muscle Spindles, Golgi Tendon Organs, & Receptors in Joint Capsules (that detect pressure, tension, and movement at the joint.). Thermoreceptors, which detect changes in temperature, some receptors detecting cold and others warmth. Pain receptors (nociceptors), which detect damage in the tissues, whether it is a physical damage or chemical damage. Electromagnetic receptors (photoreceptors), such as rods and cones which detect light on the retina of the eye. Chemoreceptors, which detect taste in the mouth (taste receptors), smell in the nose (olfactory receptors), O2 and CO2 concentrations in the blood (carotid body receptors), osmolality of body fluids (osmoreceptors), and perhaps other factors that make up the chemistry of the body. In general, clinically, senses can be classified into three types: [A] Somatic senses are the sensations arising from skin, muscles, tendons and joints. These sensations have specific receptors, which respond to a particular type of stimulus. That include; 1. Tactile sensations, that include touch, pressure, tickling, itch, the vibratory and stereognosis sensations (stereognosis is the ability to determine what an object is just by using the modality of touch). 2. Position (or proprioceptive) sensation. 3. Pain sensation. 4. Thermal sensation. [B] Special senses: Special sensations are the complex sensations for which the body has some specialized sense organs. They include vision, smell, taste, hearing, and equilibrium sensations (rotational and linear acceleration). [C] Visceral sensations: Which are those concerned with perception of the internal environment such as those receptors which detect the changes in the osmolarity of the plasma (osmoreceptors), the pH, and other body fluids chemistry and pressure (chemoreceptors, baroreceptors). 5 Mustansiriyah College of Medicine General properties of receptors: 1. The sensitivity of receptors: Each type of receptor is very highly sensitive to one type of stimulus (or particular type of energy) for which it is designed. A sensory receptor can be activated by variety of stimuli but the threshold for each of these stimuli varies considerably. The stimulus or the energy for which a sensory receptor is most sensitive (lowest threshold for detection) is called the adequate stimulus. 2. The specificity of the nerve fiber attached to the receptor: Each nerve fiber is specialized to transmit only one modality of sensation (a labeled line). Each nerve tract terminates at a specific point in the CNS, and the type and the site of sensation felt when a nerve fiber is stimulated is determined by this point in the CNS to which the fiber leads no matter how or where along the pathway the activity is initiated. An example is seen in patients with amputated limb who may complain of pain and other sorts of sensations in the absent limb a condition called phantom limb. The ends of the nerves cut at the time of amputation often form nerve tangles called neuromas. These may discharge spontaneously or when pressure is put on them. The impulses that are generated are in nerve fibers that previously came from sense organs in the amputated limb, and the sensations evoked are projected to where the receptors used to be. 3. The ability to generate a receptor potential (generator potential): The mechanism used by the receptor to produce the receptor potential varies depending on the type of receptor. The stimulus that excites the receptor: [A] May activate second messenger systems (such as Ca ions, cAMP, or cGMP) or, [B] It may increase or decrease the permeability of the receptor membrane to ions such as Na and K ions without involvement of a second messenger. All these mechanisms change the transmembrane potential. This local graded change in the membrane potential of the receptor is called receptor potential or generator potential (depolarization) except in the photoreceptors where the light causes hyperpolarization. When receptor potential rises at or above the threshold level, action potential starts to be elicited and propagated along the nerve fiber attached to the receptor. As the stimulus intensity increases, the receptor potential increases, and as the receptor potential increases, the impulse rate in the nerve fiber (the frequency of action potentials) increases. Therefore, the impulse rate is proportional to the stimulus intensity. However, the impulse rate in the nerve fiber is directly proportional to the low intensities of the applied stimuli (at low intensity field) and less steep when the intensities of the applied stimuli are high (at high intensity field). The brain can recognize the intensity of the stimulus that is transmitted to it by: [A] Variation in the frequency of the action potential generated by the activity in a given receptor (called temporal summation, or frequency coding) and [B] By variation in the number of receptor activated (called spatial summation or population coding). 6 Mustansiriyah College of Medicine 4. Adaptation or desensitization of receptors: It is a progressive decrease of receptor response to the continuous application of a constant sensory stimulus. When a continuous sensory stimulus is applied, the receptors respond at first with a very high impulse rate, and then at a progressively lower rate until finally many of them no longer respond at all. The time for adaptation is quite variable in different types of receptors ranging from few thousandths of a second to few days. According to the period for adaptation, sensory receptors can be divided into: A. Tonic receptors: They are slowly and incompletely adapting receptors. These types of receptors continue transmitting impulses to the brain as long as the stimulus is present or at least for many minutes or hours. Therefore, they keep the brain constantly appraised of the status of the body and its relation to its surroundings. Examples of such receptors are the joint capsule receptors, muscle spindles, Golgi tendon apparatuses, the receptors of the macula in the vestibular apparatus, the pain receptors, and baroreceptors of the arterial tree, the chemoreceptors of the carotid and aortic bodies, and some of the tactile receptors. B. Phasic receptors: They are rapidly and completely adapting receptors. These receptors are stimulated only when the stimulus intensity changes. Furthermore, the number of impulses transmitted is directly related to the rate at which the change takes place. For instance, in the case of pressure receptors, sudden pressure applied to the skin excites this receptor for a few milliseconds, and then its excitation is over even though the pressure continues. But then it transmits a signal again when the pressure is released. 5. Sensory unit: A single sensory axon with its branches forms the sensory unit. When a stimulus is applied, a response is produced from the region of the area that is stimulated. This is called receptive field. As the stimulus intensity is increased, more and more sensory units are activated and this is called recruitment of sensory units. It should be remembered that a sensory unit of one type of receptor could overlap with the sensory units of other types of receptors in the skin. This overlapping of sensory units from other receptors will also be stimulated when the intensity of stimulus is increased. Tactile sensations: Mechanoreceptors specialized to receive tactile Information. Four major types of encapsulated mechanoreceptors are specialized to provide information to the central nervous system about touch, pressure, itch, tickle, vibration, and stereognosis: Meissner’s corpuscles, Pacinian corpuscles, Merkel’s disks, and Ruffini’s corpuscles. These receptors are referred to collectively as low- threshold (or high-sensitivity) mechanoreceptors because even weak mechanical stimulation of the skin induces them to produce action potentials. They are frequently classified as separate sensations but they are all detected by the same type receptors which may differ histologically. Touch and pressure: Pressure is sustained touch. Touch receptors are most numerous in the skin of the fingers and lips and relatively scarce in the skin of the trunk, and they are found around hair follicles in addition to the subcutaneous tissues of hairless areas. Touch sensation is carried by type A and C nerve fibers. Itch and tickle: Relatively mild stimulation of the skin, eyes, and certain mucous membranes produces itch and tickle sensations carried by type C nerve fibers. Scratching relieves itching because it activates afferent fibers that block transmission (through lateral inhibition) of the itch carrying fibers at the dorsal horn of the spinal cord. Itching can be produced by repeated local mechanical stimulation of the skin and by variety of chemical agents such as bile salts, histamine, and kinins. Vibratory sensation: All the different tactile receptors are involved in detection of vibration between 60 up to 700 cycles/sec. Vibratory sensation is conducted by type A nerve fibers. Vibratory and proprioceptive sensations are closely related, when one is depressed, so is the other. Stereognosis: The sense of touch that is essential for perception of form, shape, and spatial nature of objects. Tactile sensors are located predominantly in the palm, especially in the fingertips, and 7 Mustansiriyah College of Medicine in the tongue and oral cavity. Stereognostic perception of an object requires that the CNS integrate signals from adjacent receptors into a spatial pattern and coordinate them with tactile motor function. Synthetic senses are the sensations synthesized at cortical level, by integration of impulses of basic sensations. Require synthesis and interpretation of primary modalities by the sensory association area in the parietal lobe. Best examples of synthetic senses are stereognosis and two-point discrimination (double simultaneous stimulation), graphaesthesia, barognosis (the ability of evaluating the weight of objects), localization of touch (topognosis). The position (or proprioceptive) sense: Proprioceptive (or position) sensations are the sensations of the physical state of the body, including position and movement sensations. It is carried by type A nerve fiber. They involve the sensory signals from the tendons, muscles, the joint capsules, ligaments, skin, deep tissues near the joints, pressure sensations from the bottom of the feet, and even the sensation of equilibrium (vestibular system). Proprioceptive sensation is either conscious and is carried by lemniscal pathway or subconscious and is carried by spinocerebellar tract (as will described later). It can be divided into two subtypes: 1. Static proprioceptive sensation, which means conscious recognition of the orientation of the different parts of the body with respect to each other and, 2. Dynamic proprioceptive sensation (Kinesthesia), which means conscious recognition of movements and the rates of movement of the different parts of the body. Pain sensation: An unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is a protective mechanism for the body and protects your body from injury (or further injury if you have already hurt yourself). Pain also helps healing...because an injury hurts, you rest. It occurs whenever any tissues are being damaged, and it causes the individual to react to remove the pain stimulus. There are two types of pain; acute pain (sharp or pricking or fast or electrical pain) as in cut finger and chronic pain (burning or aching or throbbing or nauseous or slow pain) as in sunburn. Acute pain often results from tissue damage, such as a skin burn or broken bone. Acute pain can also be associated with headaches or muscle cramps. This type of pain usually goes away as the injury heals or the cause of the pain (stimulus) is removed. Chronic pain refers to pain that persists after an injury heals, cancer pain, pain related to a persistent or degenerative disease, and long- term pain from an unidentifiable cause, for example, the stimulus cannot be identified in as many as 85% of individuals suffering lower back pain.. There are some people who are born WITHOUT the sense of pain. These people have a rare condition called "congenital insensitivity to pain". Their nervous systems are not equipped to detect painful information. You may think this is a good thing....it is NOT. Without the ability to detect painful events, you would continue to cause injury to yourself. For example, if you broke a bone in your arm, you might continue using the arm because it did not hurt. You could cause further injury to your arm. People with congenital insensitivity to pain usually have many injuries like pressure sores, damaged joints and even missing or damaged fingers! 8 Mustansiriyah College of Medicine Acute (fast) pain Chronic (slow) pain Occurs within about 0.1 sec after a pain stimulus is applied. Often results from Occurs after a sec or more and then increases slowly over a tissue damage, such as a skin burn or period of many sec and sometimes even minutes. Chronic pain broken bone. This type of pain usually goes persists after an injury heals, cancer pain, pain related to a away as the injury heals or the cause of the persistent or degenerative disease and long-term pain pain (stimulus) is removed. from an unidentifiable cause. It is felt in the skin and can be highly It is felt both in the skin and in almost any internal tissue and it is localized (superficial pain). very grossly localized (deep pain) It transmitted through type Aδ pain It transmitted through type C pain fibers which can be blocked fibers which can be blocked by moderate by low concentrations of local anesthetic. compression of the nerve fiber. Glutamate is the probable neurotran- Substance P is the probable neurotransmitter. Inhibition of the smitter release of substance P is the basis for pain relief by opioids. 1st order neurons terminate mainly in 1st order neurons terminate almost entirely in lamina II and III of lamina I at the dorsal horn and these excite dorsal horns of spinal cord, together called as substantia second order neurons gelatinosa. The 2nd order neuron is terminated in The 2nd order neuron is terminated in the thalamus but gives the thalamus. collateral to reticular formation, periaqueductal gray area, and hypothalamus. It evokes a withdrawal reflex and a sympathetic response, including an It produces nausea, profuse sweating, a lowering of blood increase in blood pressure and a pressure, and a generalized reduction in skeletal muscle tone. mobilization of body energy supplies. Because of this double system of pain innervation, a sudden onset of painful stimulus gives a double pain sensation: a fast sharp pain followed a second or so later by a slow burning pain. The sharp pain apprises the person very rapidly of a damaging influence and making the person to react immediately to remove himself from the stimulus. On the other hand, the slow pain sensation tends to become more and more painful over a period of time. Types of pain receptors: The pain receptors (nociceptors) are all free nerve endings and are of tonic type. Pain receptors can be classified into 3 types according to the type of stimulus that excite them and these are: 1. Mechanosensitive pain receptors: They are excited almost entirely by excessive mechanical stress or damage to the tissues. 2. Thermosensitive pain receptors: They are sensitive to extreme of heat or cold. 3. Chemosensitive pain receptors: They are sensitive to various chemical substances released at sites of injury and cause direct extreme stimulation of pain nerve fibers without necessarily damaging them such as Substance P, lactic acid, bradykinin, serotonin (or 5HT from platelets), histamine (from mast cells), potassium ions ( from damaged Cells), acids, prostaglandins (from arachidonic acid released from damaged cells), acetylcholine. Proteolytic enzymes are actually cause direct damage to the pain nerve endings. Aspirin and other non-steroidal anti-inflammatory drugs (like voltaren, ponstan, and brufen) prevent the formation of prostaglandins. Since prostaglandins play a role in sensitization of pain nerve fibers and without them, the nociceptors are less likely to become sensitized and therefore less pain impulses will be transmitted. 9 Mustansiriyah College of Medicine Ischemia can cause pain due to [l] accumulation of large amounts of lactic acids in the tissues and due to the production of other chemical agents from the tissues as a result of the cell damage. Muscle spasm can cause pain either [l] directly due to stimulation of mechanosensitive pain receptors and indirectly by causing ischemia (by compression the blood vessels and diminishes blood flow and by increasing the metabolic rate in the muscle tissue at the same time) and thereby stimulating chemosensitive pain receptors. Referred pain: That is the pain felt in a part of the body considerably remote from the tissues causing the pain. Usually the pain is initiated in one of the visceral organs and referred to an area on the body surface or deep area of the body not exactly coincident with the location of the viscus producing the pain. The best known example is referral of cardiac pain to the inner aspect of the left arm. Other examples include pain in the tip of the shoulder owing to irritation of the central portion of the diaphragm and pain in the testicle due to distortion of the ureter. The mechanism of the referred pain is as follow: The visceral pain fibers enter the spinal cord and synapse with second order neuron that also receives pain fiber from the skin. When the visceral pain fibers are stimulated, pain signals from the viscera are then conducted through the same spinal neurons that conduct pain signals from the skin, and person has the feeling that the sensations actually originate in the skin itself. The rules that determine the areas to which the pain is referred are: 1. Dermatomal rule: In which the pain is usually referred to a structure that developed from the same embryonic segment or dermatome in which the pain originates. For example, during embryonic development, the diaphragm migrates from the neck region to its adult location in the abdomen and takes its nerve supply, the phrenic nerve, with it. The afferent fibers of the phrenic nerve enter the spinal cord at the level of the second to fourth cervical segments, the same location at which afferents from the tip of shoulder enter. 2. Brain interpretation rule: Pain signals from visceral structure may converge on the same spinothalamic tract that receives sensory somatic signals from the peripheral structures. Since somatic pain is much more common than visceral pain, the brain has learned that activity arriving in a given pathway is caused by a pain stimulus In a particular somatic area. 3. Facilitation effects rule: In which the incoming impulse from visceral structures lower the threshold of spinothalamic neurons receiving afferent from somatic areas, so that minor activity in the pain pathways from the somatic areas passes on to the brain. Visceral pain: It is the pain from different viscera of the abdomen and chest. The true visceral pain is transmitted through type C nerve fibers that run in the sympathetic or parasympathetic nerves. The 10 Mustansiriyah College of Medicine viscera have somatic receptors for pain sensation only. Because there are relatively few pain receptors in the viscera, visceral pain is poorly localized. Visceral pain is different from surface pain and that is a highly localized types of damage to the viscera rarely cause pain. On the other hand, any stimulus that causes diffuse stimulation of pain nerve endings throughout a viscus causes pain that can be extremely severe. Such stimuli include ischemia of visceral tissue, chemical damage to the surface of the viscera, spasm of the smooth muscle in a hollow viscus, distention of a hollow viscus, or stretching of the ligaments. The brain, the parenchyma of the liver and the alveoli of the lungs are almost entirely insensitive to pain of any type. Yet, the liver capsule, the bile ducts, the bronchi, the parietal pleura, parietal peritoneum, and pericardium are very sensitive to pain. This is because these structures are supplied with extensive innervation from the spinal nerves. There is evidence that some of the 1st order neuron of the visceral pain fiber terminate the intermediate gray region of the spinal cord near the central canal. These neurons, in turn, synapse with the 2nd order neuron that send their axons not through the anterolateral white matter of the spinal cord (as might be expected for a pain pathway) but through the dorsal columns ipsilaterally in a position very near the midline. These second order axons then synapse in the gracilis nucleus of the medulla, where the third-order neurons give rise to fibers that form the contralateral medial lemniscus and eventually synapse at diffuse nuclei of thalamus. From the thalamus, a fourth-order neuron projects to cerebral cortex. Central inhibition of pain: Pain perception is affected by a variety of psychological factors such as mood and emotional motivational state. For example, under “fight and flight” condition, the threshold for pain increases such that stimuli that usually produce pain are not perceived as painful. Opposite phenomenon also occurs. For example, when a subject is anxious, a non-painful stimulus may perceive as painful. The degree to which each person reacts to pain varies tremendously. There is individual variation in response to pain, which is influenced by genetic makeup, cultural background, age and gender. The variation of patient`s reaction to pain is due to partly from the capability of the brain itself to control the degree of input of pain signals to the NS by activation of a pain control system, called analgesia system and partly by stimulation of large sensory fibers from the peripheral tactile receptors. 1- Analgesia system: It consists of three major components and these are: [A] The neurons of periaqueductal gray area. 11 Mustansiriyah College of Medicine [B] Neurons of raphe magnus nucleus. [C] Pain inhibitory complex located in the dorsal horns of the spinal cord, the areas called marginal nucleus (MN, or layer I) for fast pain (acute) and substantia gelatinosa (SG, or layers II, III, IV) for slow pain (chronic). [D] plus other accessory components (such as periventricular nuclei around the third ventricle and medial forebrain bundle in the hypothalamus). In the reticular formation, noradrenergic neurons projected from the locus ceruleus and dopaminergic neurons projected from the ventral tegmental area also appear to be involved to suppress incoming pain signals at the spinal level. The neurons of periaqueductal gray area (which secrete enkephalin as neurotransmitter) can be stimulated or inhibited via thalamus by the limbic system and prefrontal cortex of the brain. The neurons of periaqueductal gray area send their signals to neurons of raphe magnus nucleus. Those fibers originating in this nucleus descend in both lateral and ventral columns and terminate in the interneurons of the pain inhibitory complex of the spinal cord secrete serotonin at their endings which stimulate these interneurons to secrete enkephalin. The enkephalin, in some way is believed to cause presynaptic and postsynaptic inhibition of the incoming pain fibers in the dorsal horns. At this point the pain signals can be blocked before they are relayed on to the brain. Presynaptic Inhibition probably achieved by blocking Ca channels in the membranes of the nerve terminal. It was found that these areas of the analgesia system have opiate receptors which interact with morphine (an opiate substance) and with some morphine-like neurotransmitters that is naturally secreted in the brain such as beta- endorphin which is found in hypothalamus and pituitary gland, met- and leu- enkephalin which are found in analgesia system, and dynorphin which is present in only minute quantities in nervous tissue, but having 200 times as much pain- killing effect as morphine when injected directly into the analgesia system. In addition, multiple areas of the brain have been shown to have opiate receptors. 2- Stimulation of peripheral sensory fiber (gate control theory): Cells in substantia gelatinosa (SG) act as the “gate”. Stimulation from large fibres (A fibers) causes the gate to close due to stimulation of inhibitory 12 Mustansiriyah College of Medicine interneuron that inhibits the pain incoming nerve fiber (cells in SG are stimulated, decrease pain signal). Stimulation from small fibers (C fibers) opens gate due to inhibition of inhibitory interneuron (cells in SG are inhibited, increase pain signal). Stimulation of large sensory fibers from the peripheral tactile receptors (such as massage or acupuncture) depresses the transmission of pain signals either from the same area of the body or even from areas sometimes located many segments away. As these sensory tactile fibers enter the dorsal column of the spinal cord give collateral fibers to the dorsal horn of the cord. Impulses in these collateral or interneurons on which they end inhibit transmission from the dorsal root pain fibers to the spinothalamic neurons. Thermal Sensations: Thermal sensations are detected by two different types of subcutaneous sensory receptors. Therefore, the subcutaneous temperature actually determines the responses. There are two types of thermal receptors and these are: The cold receptors which respond maximally to temperature slightly below body temperature. This will be seen until the temperature reaches 10o C. Temperature beyond this will not stimulate the thermoreceptors, but stimulates the nociceptors which give pain sensation. The warmth receptors which respond maximally to temperature slightly above body temperature. The rise in the body temperature above 45o C stimulates the nociceptors and gives pain sensation. Both the types of (cold and warm) receptors are stimulated when the body temperature is between 31 to 38o C. This range of temperature is called neutral zone, where adaptation is present. The cold sensation is carried by the Aδ and C, whereas, the warm is carried by only C fibers. In most areas of the body there are three to ten times as many cold receptors as warmth receptors. The person determines the different gradations of thermal sensations by the relative degrees of stimulation of the different types of receptors. Because the number of cold or warmth receptors in any one surface area of the body is very slight, it is difficult to judge gradations of temperature when small areas are stimulated. The judgment of gradation is increased as the stimulated surface area increases. The thermal receptors respond markedly to changes in temperature in addition to being able to respond to steady states of temperature (i.e. they are tonic and at the same time phasic type of receptors). This means that when the temperature of skin is actively falling, a person feels much colder than when the temperature remains at the same level. Conversely, if the temperature is actively rising the person feels much warmer than he would at the same temperature if it was constant. Almost all the afferent sensory somatic information of the body enters the spinal cord through the dorsal roots of the spinal nerves or the brain stem via the cranial nerves. On entering the spinal cord the sensory signals are carried to the brain by three sensory pathways: 1. The dorsal column pathway (medial lemniscal system): In which: [A] First order neurons (dorsal root sensory fibers) enter the dorsal column of the spinal cord and then pass up on the same side of its entrance in the spinal cord to the medulla, where they synapse in the cuneate and gracile nuclei. 13 Mustansiriyah College of Medicine [B] From the cuneate and gracile nuclei the second order neurons are originated and decussate immediately to the opposite side and then pass upward to the thalamus through medial leminisci pathways which is joined by additional decussated fibers from the sensory nucleus of the trigeminal nerve. [C] From thalamus, third order neurons project mainly to the somatic sensory area located at postcentral gyrus and occupy the cerebral cortex of the anterior portion of the parietal lobe. The dorsal column carries the following sensations: fine touch and pressure (including weight, shape, Size, texture), vibration, stereognosis, and conscious proprioception (sense of position and movements of different parts of body). 2. The anterolateral pathways (spinothalamic pathway): In which: [A] First order neurons (dorsal root sensory fibers) enter the dorsal horns of the spinal cord and synapse with the second order neurons. The afferent fiber in the peripheral nerve, which enters the spinal cord via the dorsal root, ascends and descends approximately two spinal segments in the tract of Lissauer (also called posterolateral tract) prior to synapse in the dorsal horn gray matter. Tract of Lissauer is a small strand capping the posterior horn close to the entrance of the posterior nerve roots. It is present throughout the spinal cord, and is most developed in the upper cervical regions. During a complete occlusion of the anterior artery of the spinal cord, it is the only tract spared along with the dorsal columns. The tract of Lissauer is involved with neurological deficits seen in pernicious anemia. [B] The second order neurons cross to the opposite anterolateral white column where they turn upward toward the thalamus through anterior and lateral spinothalamic tracts. Some of the second order neurons of the anterolateral system, which carry signals from slow C pain fibers, give collateral fibers to reticular formation, periaqueductal gray area, and hypothalamus. Because of the ascending and descending tracts of Lissauer, the site of decussation for the anterolateral tract is within 1– 2 spinal cord segments above and below the level where the peripheral afferent neuron enters the spinal cord. Thus, any unilateral damage to the ALS tract will result in a contralateral loss of sensation beginning 1–2 spinal cord segments below the level of the lesion. [C] From thalamus, third order neurons project mainly to the somatic sensory area of the cortex along with the neurons of the dorsal column. The course of the somatic sensations through the spinal cord. A= The dorsal column pathway. B = The anterolateral pathways. 14 Mustansiriyah College of Medicine The anterolateral system carries the following sensations: crude touch and pressure, pain, thermal, tickle, itch, and sexual sensations. In general, the sensations that transmitted rapidly, and with fine gradations of intensity and highly localized to exact points in the body are transmitted in the dorsal system. While those sensations which do not transmit rapidly, and lack of fine gradations, and poorly localized to exact points in the body are transmitted in the anterolateral system. Signs of lesions of the central sensory pathways: A lesion confined to the posterior column of the spinal cord will cause:  Loss of position and vibration sense on the same side, but the sensation of pain, touch, temperature will be preserved.  The loss of the sense of the position causes sensory ataxia (muscle incoordination) and the patient has difficulty on standing in upright balanced position with the feet close together without swaying (Romberg’s test) due to loss of proprioceptive sensations. This type of ataxia is more marked when the eyes are closed. The same symptoms will be found if the first order neurons of the proprioceptive nerve fiber are damaged peripherally but they will then be associated with other signs of peripheral nerve disease. Lesions of the spinothalamic tracts cause impairment of the ability to appreciate pain and temperature on the contralateral side of the body below the level of the lesion. Touch is usually modified (it feels different) but not abolished because of its alternative pathway in the posterior columns. In the brain stem, the spinothalamic tract and medial lemniscus run close together. Therefore, lesion of the upper brain stem usually affects all forms of sensation on the contralateral side of the body. Lesions of the main sensory nuclei of the thalamus may cause:  Loss of various modalities of sensation on the opposite side of the body.  And spontaneous pain of most unpleasant quality in the opposite side of the body which often causes considerable emotional reaction. 15 Mustansiriyah College of Medicine 3. The spinocerebellar pathways: They carry proprioceptive information from Golgi tendon organs and muscle spindles. All of these first order neurons have their cell bodies in the dorsal root ganglion. They pass through the dorsal horn to form synapses with second order neurons. Second order neurons pass through the spinal cord as:  Dorsal spinocerebellar tract: Axons of second order neurons reach lateral column of same side (ipsilateral). Then, these fibers ascend through other spinal segments and reach medulla oblongata. From here, the fibers reach cerebellum through inferior cerebellar peduncle. Lesion of this tract causes unilateral loss of the subconscious kinesthetic sensation occurs in lesion of this tract on the same side, as this tract has uncrossed fibers.  Ventral spinocerebellar tract: Ventral spinocerebellar tract contains both crossed and uncrossed fibers. Majority of the fibers of second order neurons cross the midline and ascend in lateral white column of opposite side. Some fibers ascend in the lateral white column of the same side also. Finally, the fibers reach the cerebellum through the superior cerebellar peduncle. Lesion of this tract leads to loss of subconscious kinesthetic sensation in the opposite side. In general, the same principles apply to transmission in the anterolateral pathway as in the dorsal column-medial lemniscal system, except for the following differences: (1) the velocities of transmission are only one-third to one-half those in the dorsal column-medial lemniscal system, ranging between 8 and 40 m/sec; (2) the degree of spatial localization of signals is poor; (3) the gradations of intensities are also far less accurate, most of the sensations being recognized in 10 to 20 gradations of strength, rather than as many as 100 gradations for the dorsal column system; and (4) the ability to transmit rapidly changing or rapidly repetitive signals is poor. NOTE: PROPRIOCEPTIVE SENSATION IS EITHER CONSCIOUS AND IS CARRIED BY LEMNISCAL PATHWAY OR SUBCONSCIOUS AND IS CARRIED BY SPINOCEREBRAL TRACT. Layers of the cerebral cortex: The cerebral cortex contains six separate layers of neurons, beginning with layer I next to the surface and extending progressively deeper to layer VI. Each layer performs functions different from those in other layer. For examples: The cerebral cortex contains six layers of neurons, beginning with layer I next to the brain surface and extending progressively deeper to layer VI. As would be expected, the neurons in each layer perform functions different from those in other layers. Some of these functions are: 1. The incoming sensory signal excites neuronal layer IV first; then the signal spreads toward the surface of the cortex and also toward deeper layers. 2. Layers I and II receive diffuse, nonspecific input signals from lower brain centers that facilitate specific regions of the cortex (ARAS). This input mainly controls the overall level of excitability of the respective regions stimulated. 3. The neurons in layers II and III send axons to related portions of the cerebral cortex on the opposite side of the brain through the corpus callosum. 4. The neurons in layers V and VI send axons to the deeper parts of the nervous system. Those in layer V are generally larger and project to more distant areas, such as to the basal ganglia, brain stem, and spinal cord, where they control signal transmission. From layer VI, especially large numbers of axons extend to the thalamus, providing signals from the cerebral cortex that interact with and help to control the excitatory levels of incoming sensory signals entering the thalamus. Functionally, the neurons of the somatic sensory cortex are arranged in vertical columns extending all the way through the six layers of the cortex. Each of these columns serves a single specific sensory modality, some responding to stretch receptors around Joints, some responding to tactile 16 Mustansiriyah College of Medicine stimulation, etc. Furthermore, the columns for the different modalities are interspersed among each other to allow the beginning of analysis of the meanings of the sensory signals. The corpus callosum plays an essential role in integrating the activity of the two cerebral hemispheres: Sensory information from the right half of the body is represented in the somatosensory cortex of the left hemisphere and vice versa. Equally, the left motor cortex controls the motor activity of the right side of the body. Despite this apparent segregation, the brain acts as a whole, integrating all aspects of neural function. This is possible because, although the primary motor and sensory pathways are crossed, there are many cross-connections between the two halves of the brain, known as commissures. As a result, each side of the brain is constantly informed of the activities of the other. The largest of the commissures is the vast number of fibers that connect the two cerebral hemispheres, known as the corpus callosum. Experimental work has shown that most of the nerve fibers that traverse the corpus callosum project to comparable functional areas on the contralateral side. It was subsequently found that epileptic discharges can spread from one hemisphere to the other via the corpus callosum and that major epileptic attacks can involve both sides of the brain. In a search for a cure for the severe bilateral epilepsy experienced by some patients, their corpus callosum was cut by the human split-brain operation. This had the desired end result in a reduction in the frequency and severity of the epileptic attacks. It also offered the opportunity of careful and detailed study of the functions of the two hemispheres of the human brain. 17 Mustansiriyah College of Medicine Higher interpretation of sensory signals: This is achieved by the cerebral cortex in the following areas: Primary sensory areas. Sensory association areas. Wernicke's area. Primary sensory areas: They include:  Primary somatic sensory area.  Primary visual sensory area.  Primary auditory sensory area. They are the areas of the cerebral cortex to which the respective sensory signals are projected. They have spatial localization of signals from peripheral receptors. These areas analyze only the simple aspects of sensations and that is to inform the brain that a sensory signal is actually arrived to the cerebral cortex but they are not able of complete analysis of complicated sensory patterns. Despite the inability of the primary sensory areas to analyze the incoming sensations fully, when these primary areas are destroyed the ability of the person to utilize the respective sensations usually suffers drastically. In the primary somatic sensory area the spatial orientation of the different parts of the opposite side of body were represented. The size of the area of representation is directly proportional to the number of specialized sensory receptors in each respective peripheral area of the body. For instances, the lips are by far the greatest of all, followed by the face and thumb, whereas the entire trunk and lower part of the body are represented by relatively small areas. Yet, cortical lesions do not abolish somatic sensation. Thus, perception may occur at subcortical level and it is possible in the absence of the cortex. Therefore, wide spread excision of primary somatic sensory area may lead to the following signs:  The person is unable to localize discretely the different sensations in the different parts of the body.  He is unable to judge exactly the 18 Mustansiriyah College of Medicine degrees of pressure against his body.  He is unable to judge exactly the weights of objects.  He is unable to judge shapes or forms of objects.  He is unable to judge texture of materials. Sensory association areas: That include:  Somatic sensory association area.  Visual sensory association area.  Auditory sensory association area. Around the borders of the primary sensory areas are regions called sensory association areas. The general function of the sensory association areas is to provide a higher level of interpretation of the sensory signals. In these areas, interpretation of the sensory signals is achieved by giving the brain the simplest meaning and characteristic of the sensory signal. Destruction of the sensory association area greatly reduces the capability of the brain to analyze and interpretate different characteristics of sensory experiences. Damage to the sensory association area is associated with specific deficits known as agnosias. Sensory somatic association area is located in the parietal cortex behind primary somatic sensory area. It plays important roles in deciphering the sensory information that enters the primary somatic sensory area by combining information from multiple points in the primary somatic sensory area to decipher its meaning. Damage can affect the ability to recognize objects even though the objects can be felt (tactile agnosia). Loses the ability to recognize complex objects and complex forms by the process of feeling them is called astereognosis, even though there is no specific sensory deficit. Stereognosis is the ability to determine what an object is just by using the modality of touch. Wernicke's area: It is the area where the sensory association areas all meet one another in the posterior part of the temporal lobe where temporal, parietal, and occipital lobes all come together. This area is called Wernicke’s area which converge the different sensory interpretative areas. It is highly developed in the dominant side of the brain (left side) and plays the greatest role in interpretation of the complicated meanings of different sensory experiences. 19 Mustansiriyah College of Medicine Somatomotor functions of the CNS 20 Mustansiriyah College of Medicine Descending pathways involved in motor control The brain communicates with the spinal motor circuitry through two major groups of descending pathways, named according to their location in the spinal white matter. 1. The lateral pathways are concerned with voluntary movement of the distal muscles (e.g., muscles of the arm and hand). There are two major pathways in this group, the corticospinal tract and the rubrospinal tract. [A] The lateral corticospinal tract, [B] The rubrospinal tract, [C] The lateral medullary reticulospinal tracts, [D] The lateral vestibulospinal tract, 2. The ventromedial pathways originate in the brainstem and innervate the proximal and axial muscles to help maintain head position and posture, muscle tone and gross movements of the neck, trunk, and proximal limb muscles. Sensory information about the body position and balance is derived from the visual and vestibular systems and is conveyed via three major tracts: [A] The anterior corticospinal tract, [B] The tectospinal tract, [C] The medial pontine reticulospinal tracts, [D] The medial longitudinal fasciculus NOTE: The medial longitudinal fasciculus links the three main nerves which control eye movements, i.e. the oculomotor, trochlear and the abducent nerves, as well as the vestibulocochlear nerve. The purpose of the medial longitudinal fasciculus is to integrate movement of the eyes and head movements. The motor functions of the CNS can be divided into:  Movement, There are three classes of movements: [a] Reflexes which are involuntary, rapid, stereotyped movement such as eye-blink, coughing, knee jerk and graded control by eliciting stimulus. [b] Voluntary movement which is complex actions such as reading, writing, playing piano. They are purposeful, goal-oriented and learned type of activity which can be improved with practice. [c] Mixed pattern which combine voluntary & reflexive acts such as chewing, walking, running. It is initiated and terminated voluntarily, but once initiated it become repeatitive and reflexive.  Posture and balance,  Communication. Reflexes: The basic unit of reflexes is the reflex arc. The arc consists of a sense organ (receptor), an 21 Mustansiriyah College of Medicine afferent neuron, one or more synapses in a central integrating station or sympathetic ganglion, an efferent neuron, and an effector. The connection between the afferent and efferent neurons is generally in the brain or spinal cord. The afferent neurons enter via the dorsal roots or cranial nerves and have their cell bodies in the dorsal root ganglia or in the homologous ganglia on the cranial nerves. The efferent fibers leave via the ventral roots or corresponding motor cranial nerve. The connection between the afferent and the efferent neurons is usually in the central nervous system and activity in the reflex arc is modified by multiple inputs converging on them from higher motor control centers. The spinal cord reflexes: Sensory signals enter the cord through the sensory roots. After entering the cord, every sensory signal travels to two separate destinations: 1. The sensory nerve or its collateral terminate in the gray matter of the cord and elicit local segmental motor responses. 2. The signals travel to higher and lower segmental levels of the cord itself or to the brain stem or even to the cerebral cortex. Each segment of the spinal cord has several millions neurons in its gray matter and these are: A. The posterior sensory neurons that we discussed previously. B. The anterior motor neurons: These gives rise to the nerve fibers that leave the cord via the anterior roots and innervate the effector such as skeletal muscle fibers. The cells of the anterior horn of spinal cord or motor cranial nuclei and their efferent fibers that run to motor units are also called the lower motor neurons to distinguish them from the upper motor neurons of the higher motor control centers. Thus the lower motor neuron is the final common path for all efferent impulses directed at the muscle. The anterior motor neurons are of three types: 1. The alpha motor neurons or alpha efferent neurons: Which give off large nerve fibers (type A alpha nerve fiber) that innervate the large skeletal muscle fibers (extrafusal muscle fibers) forming the motor units. 2. The gamma motor neurons or gamma efferent neurons: Which give off nerves fibers (type A gamma nerve fiber) that innervate very small special skeletal muscle fibers called intrafusal fibers which are part of the muscle spindle. 3. The interneurons: These are small neurons that have many interconnections one with the other. Most of the incoming sensory signals from the spinal nerves are transmitted first through interneurons where they are appropriately processed and then terminate on the anterior motor neurons. Some of the anterior motor neurons immediately after the motor axons leave the soma give collateral branches to innervate adjacent interneurons called Renshaw cells which are located in the ventral horn of the spinal cord. These cells in turn are inhibitory cells that 22 Mustansiriyah College of Medicine transmit inhibitory signals to the same motoneuron (recurrent inhibition) or to the nearby motor neurons (lateral inhibition).  The recurrent inhibition is important to allow only the initial impulses arriving at a motoneuron to pass through easily while the late impulses will find the anterior horn cells partially inhibited and will therefore produce a smaller motor discharge than the initial excitatory impulses. This makes what is called a "negative feedback" circuit, and presumably protects the body from accidental over activity of the motor neuron concerned, and therefore damage to the muscle it is connected to.  The lateral inhibition is to focus or sharpen the signals, i.e. to allow transmission of the primary signal while suppressing the tendency for signals to spread to adjacent neurons. The muscle receptors and their roles in muscle control: Proper control of muscle requires not only excitation of the muscle by the anterior motor neurons but also continuous feedback of information from each muscle to the nervous system which is achieved by two special types of sensory receptors and these are: 1. Muscle spindles: They are distributed throughout the belly of muscle and send information to the NS about the muscle length and the rate of change of its length. 2. Golgi tendon organs: They are located among the fascicles of a tendon between it and the muscle itself and which send information about tension or rate of change of tension. Muscle spindle: Each muscle spindle consists of 3—10 specialized muscle fibers enclosed in a connective tissue capsule. These fibers are called intrafusal muscle fibers to distinguish them from the extrafusal muscle fibers which are the regular contractile units of the muscle. The intrafusal fibers are in parallel with the rest of the muscle fibers but not for the entire length of the muscle. The central region of each of the intrafusal fibers does not contract while the ends do. The central non contractile portion of the fiber functions as a sensory receptor. There are two types of intrafusal fibers and these are nuclear chain fibers (which detect the changes in muscle length, i.e. static changes) and nuclear bag fiber (which detect the rate of change in muscle length, i.e. dynamic changes). The receptor portion of the muscle spindle is stimulated by stretch of the midportion of the spindle. This can occur as a result of: 1. Lengthening the whole muscle which will in turn stretch the mid-portions of the spindle and therefore excite the receptor. 2. Contraction of the end-portions of the intrafusal fibers by increase stimulation of gamma motor neurons that will stretch the mid-portions of the spindle and therefore excite the receptor and increases the rate of firing while shortening the mid-portion of the muscle spindle by inhibition of gamma motor fibers decreases this rate of firing. The number of impulses transmitted from the muscle spindles increases directly in proportion to the degree of stretch and the rate of change of its length and continues for as long as the receptor itself remains stretched. Normally, there is a slight amount of continuous gamma motor 23 Mustansiriyah College of Medicine excitation, consequently, the mid-portion of the muscle spindles emit sensory nerve impulses continuously. The neurons involved in various reflex arcs (both alpha and gamma motor neurons) normally receive a basal level of excitatory stimulation from the brain through the following descending tracts:  Corticospinal tract, the activation of α motor neuron during voluntary action co-activates γ efferents also, in order to maintain muscle length when extrafusal fibers contract.  Lateral vestibulospinal tracts to stimulate extensor (antigravity) muscles, and inhibit flexors.  Pontine reticulospinal tract.  Rubrospinal tract (excites flexors alpha and gamma motor neurons to the distal muscles). These excitatory pathways are held in check directly or indirectly by inhibitory descending pathways on gamma motor neurons by:  Medullary reticulospinal tract (inhibitory to both alpha and gamma motor neurons).  Rubrospinal tract (inhibits extensor alpha and gamma motor neurons to the distal muscles). Therefore, the sensitivity of muscle spindles (and consequently all the spinal cord reflexes) can be modified through the increase (excitation) or decrease (inhibition) of gamma motor neurons which leads to increase or decrease the response of the muscle spindles to stretch. Other areas of the brain are also involved in the regulation of gamma motor neurons indirectly through their effect on the descending tracts such as basal ganglia (inhibitory) and cerebellum (excitatory or inhibitory).  The activity of the gamma motor neurons are also affected by anxiety which causes an increase in gamma neurons discharge.  In addition, stimulation of the skin, especially by noxious agents, increases gamma efferent discharge to ipsilateral flexor muscle spindles while decreasing that to extensors and produces the opposite pattern in the opposite limb.  It is well known that trying to pull the hands apart when the flexed fingers are hooked together facilitates the knee jerk reflex (Jendrassik’s maneuver or reinforcement) and this may be due to increased gamma efferent discharge initiated by afferent impulses from the hands.  When Corticospinal and corticoreticular projections are damaged with an intact of the vestibular nuclei and vestibulospinal tract are intact, gamma neurons discharge is increased. This is due to:  Unopposed activity of vestibulospinal tracts (excitatory) and,  Continuous activity of pontine reticular formation (excitatory) on the gamma motor neurons by strong stimulation of cerebellum, vestibular nuclei, and signals from peripheral somatosensory receptors.. 24 Mustansiriyah College of Medicine  When only corticospinal fibers are damaged with an intact of corticoreticular and reticulospinal projections, no change in gamma neurons discharge was observed. This is due to the existence of both pontine (a tonic excitatory structure) and medullary (inhibitor) reticulospinal tract.  Spinal cord transection and spinal shock: When the spinal cord is suddenly transected, essentially all cord functions immediately become depressed, a reaction called spinal shock. The results are paraplegia (loss of voluntary movements below the level of the lesion due to interruption of the descending pathway from the motor centers in the brain stem and higher centers), loss of conscious sensation below the level of the lesion, and initial loss of reflexes. The reason for this initial loss of reflexes is that normal activity of the cord neurons depends to a great extent on continual excitatory tonic discharges from higher centers, particularly discharges transmitted through the corticospinal tracts, pontine reticulospinal tracts and vestibulospinal tracts. After a few hours or a few days or weeks of spinal shock, the spinal neurons gradually regain their excitability and may become relatively hyperactive. The recovery of reflex excitability may possibly be due to the development of denervation hypersensitivity to the mediators released by the remaining spinal excitatory endings. Another possibility for which there is some evidence is the sprouting of collaterals from existing neurons, with the formation of additional excitatory endings on interneurons and motor neurons. If the lesion is at C7, there will be loss of sympathetic tone to the heart. As a result, heart rate and arterial pressure will decrease. If the lesion is at C3, breathing will stop because the respiratory muscles have been disconnected from control centers in the brain stem. If the lesion is at C1 (e.g., as a result of hanging), death occurs. The stretch reflex (also called tendon reflex or deep reflex): It is a reflex mediated by the muscle spindles. When a skeletal muscle with an intact nerve supply is stretched, it contract. This is called a stretch reflex. It is the only monosynaptic reflex in the body in which a single synapse is present in the reflex arc located between the afferent and the efferent neurons. The nerve fiber originating in a muscle spindle enters the dorsal root of the spinal cord and then it passes directly to the anterior horn of the cord gray matter and synapses directly with anterior alpha motor neurons that send nerve fibers back to the same muscle from where the muscle spindle fiber originated. Via changes in the sensitivity of the 25 Mustansiriyah College of Medicine muscle spindles the threshold of the stretch reflex in various parts of the body can be adjusted and shifted to meet the needs of postural control. The time between the application of the stimulus (the stretch) and the response (muscle contraction) is called the reaction time. The spinal cord conduction time through this reflex arc is called the central delay. When a stretch reflex occurs, the muscles that antagonize the action of the muscle involved (antagonists) relax. This phenomenon is called reciprocal inhibition (or innervation). The pathway mediating this effect appears to be bi-synaptic in which a collateral branch from the afferent neuron passes in the spinal cord to an inhibitory interneuron that synapses directly on one of the motor neurons supplying the antagonist muscles. In addition, when stretch reflex occurs, the other muscles that perform, or help in perform the same set of joint motion as the agonists (synergist muscles) are also stimulated. The clinical applications of the stretch reflex are the knee-jerk and other muscle jerks. In knee- jerk, tapping the patellar tendon elicits the jerk, a stretch reflex of the quadriceps femoris muscle, because the tap on the tendon stretches the muscle. The main functions of the stretch (tendon) reflex are: [A] The establishment of muscle tone. As there is a slight amount of continuous tonic gamma motor excitation, consequently the mid-portion of the muscle spindles are continuously slightly stretched and emit sensory nerve impulses continuously, and completing the stretch reflex arc. Through this reflex arc, muscle tone is established which can be defined as a residual amount of muscle contraction even the muscle is at rest or inactivity. This residual amount of muscle contraction (muscle tone) tends to maintain the same length of the muscle by resisting stretch (the change in its length). The primary purpose of muscle tone is to keep your muscles primed and ready for action. The always activated state of partial contraction maintains balance and posture, and it also functions as a safety mechanism that allows for a quick, unconscious muscle reflex reaction to any sudden muscle fiber stretch. A. If the motor nerve to a muscle is cut, the muscle offers very little resistance to stretch and is said to be flaccid because of the cutting of the reflex arc. B. A hypotonic muscle is one in which the resistance to stretch is low due to low gamma efferent discharge. C. A hypertonic or spastic muscle is one in which the resistance to stretch is high due to high gamma efferent discharge. [B] Stabilization of body position during tense motor action: Any time a person must perform a muscle function that requires a high degree of delicate and exact positioning, excitation of the appropriate muscle spindles (through the excitation of gamma motor neuron) by signals from the facilitatory pontine reticular formation stabilizes the positions of the major joints. To do this the facilitatory pontine reticular formation transmits excitatory signals through the gamma nerve fibers to the intrafusal muscle fibers of the muscle spindles on both sides of the joint. This shortens the ends of the spindles and stretches the central receptor regions, thus increasing their signal output. As the spindles on both sides of each joint are activated at the same time, reflex excitation of the skeletal muscles on both sides of the joint also increases, producing tight, tense muscles opposing each other at the same joint. The net effect is that the position of the joint becomes strongly stabilized, and any force that tends to move the joint from its current position is opposed by the highly sensitized stretch reflex. [C] Damping or smoothing function of the stretch reflex against unsmoothed motor signals: Signals 26 Mustansiriyah College of Medicine from the spinal cord are often transmitted to a muscle in an unsmooth form, increasing in intensity for a few milliseconds, and then decreasing in intensity, then changing to another intensity level, and so forth. When the muscle spindle apparatus is not functioning satisfactorily, the muscle contraction is jerky during the course of such a signal. The stretch reflex prevents oscillation and jerkiness of the body movements induced by the unsmoothed signals from other parts of the NS. When the muscle spindle is not functioning, the muscle contraction becomes very jerky during the course of such signals. [D] Enhancement of extrafusal muscle fiber contraction (gamma loop servo system): Stretch reflex increases the degree of excitation of the extrafusal fibers. When a muscle should contract against a great load, both the alpha and gamma motor neurons are stimulated simultaneously. However, the extrafusal muscle fibers might contract less than the intrafusal fibers. This mismatch in contraction would stretch the receptor portions of the spindles and, therefore, elicit a stretch reflex that would provide extra excitation of the extrafusal fibers. The Golgi tendon organ: They are encapsulated sensory receptors and are stimulated by the tension produced by the muscle fibers. These receptors have both a dynamic and static response as those found in muscle spindles. Signals from the tendon organ are transmitted through nerve fibers to local areas of the cord, to cerebellum and to cerebral cortex. The Golgi tendon reflex (inverse stretch reflex): It is a reflex mediated by Golgi tendon organs. When the Golgi tendon organs of a muscle are stimulated by increased muscle tension due to active muscle contraction (or to much less extent passively by stretching the muscle), signals are transmitted into the spinal cord and excite inhibitory interneurons that in turn inhibit the anterior alpha motor neurons innervated the same muscle from which signals were originated. This brings about relaxation of a muscle in response to strong stretch is called the inverse stretch reflex. On the other hand, if the tension becomes too little, impulses from the tendon organ cease, and the resulting loss of inhibition allows the alpha motor neurons to become active again, thus increasing muscle tension back toward a higher level. Thus, this reflex provides a negative feedback mechanism that:  Prevents the development of too much tension on the muscle and sometimes leads to sudden relaxation of the entire muscle preventing tearing of the muscle or avulsion of tendon from its attachments to the bone.  Another function of the Golgi tendon reflex is to equalize the contractile forces of the separate muscle fibers. That is, those fibers that exert excess tension become inhibited by the reflex, whereas those that exert too little tension become more excited because of the absence of reflex inhibition. This would spread the muscle load over all the fibers and especially would prevent damage in isolated areas of a muscle where small numbers of fibers might be overloaded. Control of Golgi tendon reflex: The sensitivity of this inhibitory reflex is regulated by higher centers in the brain which adjust the set-point for muscle tension. The brain sends signals to the target muscle through alpha motor neurons to cause muscle contraction at a required tension and at the same time sends signals to the inhibitory interneurons of the cord to apprise them of the tension required in each 27 Mustansiriyah College of Medicine given muscle. Then, as the degree of contraction approaches the tension required (as detected by the feedback from the Golgi tendon organs), the inhibitory interneurons automatically inhibit the muscle contraction to prevent additional tension. In this way, the tension becomes adjusted to the set-point dictated by the brain. The withdrawal (flexor) reflex: It is an example of polysynaptic reflex in which one or more interneurons are interposed between the afferent end efferent neurons. Almost any type of cutaneous sensory stimulus (especially painful stimulus) on a limb is likely to cause the flexor muscles of the limb to contract (or contraction of other muscles), thereby withdrawing the limb from the stimulus. This is called the flexor or withdrawal reflex. The reflex arc is as follow: the painful stimulus pass into a pool of interneurons and then to the anterior motor neurons. In the interneuron pool, the signals will stimulate the following circuits: 1. Diverging circuits to spread the reflex to the necessary muscles for withdrawal. 2. Circuits to excite the ipsilateral flexor (agonist) muscles for withdrawing the limb. 3. Circuits to inhibit the ipsilateral extensor (antagonist) muscles called reciprocal inhibition circuits. 4. Circuits to cause a prolonged repetitive after-discharge even after the stimulus is over which occurs especially in very strong pain stimulus. 5. Circuits to cause crossing of the signals to the other side of the cord with reciprocal innervation (inhibition of the contralateral flexor muscles and excitation of the contralateral extensor muscles) to cause exactly opposite reactions to those that cause the flexor reflex. This type of reflex is called the crossed extensor reflex in which the opposite limb begins to extend and pushing the entire body away from the object causing the painful stimulus. The clinical applications of such a reflex are abdominal reflex, cremasteric reflexes, all of them are forms of withdrawal reflex. The higher motor control systems: The higher motor control systems involve the structures that control all motor activities executed at the brainstem level and spinal cord and these are: 1. The pyramidal system  Direct corticospinal tract: Terminates on anterior horn cells (alpha motor neurons or interneurons) in spinal cord -- pyramidal tract projects DIRECTLY to spinal cord.  Direct corticobulbar tract: Terminate on the motor nuclei of cranial nerves III, IV, V, VI, VII, IX, XI, and XII, in many cases bilaterally.  Indirect Corticospinal tract (which is part of extrapyramidal system): Terminate on the nuclei in the brainstem (specifically: vestibular, reticular, red nuclei, and tectal (superior colliculus), then project to the anterior horn cell of spinal cord as vestibulospinal, reticulospinal, rubrospinal and tectospinal tracts. The main function of these tracts is to maintain posture, balance, and the necessary BACKGROUND MUSCLE ACTIVITY (TONE); allows direct corticospinal pathway to exert its influence 2. The extrapyramidal system: It includes indirect corticospinal tracts, basal ganglia, and cerebellum. 28 Mustansiriyah College of Medicine Note: The pyramidal and extrapyramidal systems are often called upper motor neurons. Through descending spinal tracts of the upper motor neurons (mainly the pyramidal tracts, vestibulospinal tract, and reticulospinal tracts) and the activities of the basal ganglia and cerebellum, all influence directly or indirectly:. The cells of the anterior horn of spinal cord or motor cranial nuclei from which the lower motor neuron runs to motor unit. Therefore, the lower motor neuron is the final common path for all efferent impulses directed at the muscle. The inputs converging on the motor neurons bring about voluntary activity, adjust body posture to provide a stable background for movement, and coordinate the action of various muscle to make movements smooth and precise.. the transmission of neuronal impulses through spinal reflex arcs. There are two mechanisms by which descending projections may control transmission through segmental reflex arcs: [A] By their excitatory or inhibitory action on the neurons involved in the spinal reflex arc. [B] By their inhibitory action on the terminal part of afferent sensory fibers before their synapse with the next neuron (presynaptic inhibition). The pyramidal system: Which consists of the motor cortex and pyramidal (corticospinal and corticobulbar) tracts. A: The motor cortex is the area of the cerebral cortex concerned with control of body movement and it is located directly in front of the central sulcus and occupying approximately the posterior one half of the frontal lobes. The motor cortex has extensive connections with other areas of cerebral cortex and with subcortical structures (caudate nucleus, thalamus, red nucleus, pontine nuclei, olive, and lateral reticular nucleus) through its efferent fibers and also with cerebellum. The motor cortex divided into three separate divisions: The primary motor cortex The supplementary motor cortex The premotor cortex 29 Mustansiriyah College of Medicine The primary motor cortex (Brodmann area 4): This is located directly in front of the central sulcus in the precentral gyrus. From the primary motor area pyramidal motor neurons originated and send their fibers directly or indirectly to the anterior motor neurons of the spinal cord through the corticospinal tract and to the brain stem through corticobulbar tract. The pattern in the head and neck, as in the rest of the body, is that the motor cortex innervates contralateral motor nuclei. However, muscles which move the eyes, and the eyelids and forehead in association with eye movements, receive bilateral cortical innervation. The nuclei concerned are the oculomotor (III), trochlear (IV) and abducens (VI), and that portion of facial (VII) motor nucleus which innervates orbicularis oculi and frontalis. The extremities of the opposite side of the body are represented in this, with the feet at the top of the gyrus and the face at the bottom. The surface area of representation of each muscle is proportional to the skill with which the part is used in fine voluntary movement. The areas involved in speech and hand movements are especially large in the cortex. The area of motor cortex is divided into columns, each represents a movement –not a muscle- and it is crossed. Functions of the primary motor cortex: It is responsible for the execution of movement.  More than one half of the entire primary motor cortex is concerned with controlling of conscious voluntary fine, precise, discrete (separate) skilled movements of the hands and the muscles of speech which are highly developed in human being.  This area increases muscle tone by facilitation of stretch reflex. The primary motor cortex normally exerts a continual tonic stimulatory effect on the motor neurons of the spinal cord; when this stimulatory effect is removed, hypotonia results. Most lesions of the motor cortex, especially those caused by a stroke, involve not only the primary motor cortex but also adjacent parts of the brain such as the basal ganglia. In these instances, muscle spasm almost invariably occurs in the afflicted muscle areas on the opposite side of the body (because the motor pathways cross to the opposite side). This spasm results mainly from damage to accessory pathways from the non-pyramidal portions of the motor cortex. These pathways normally inhibit the vestibular and reticular brain stem motor nuclei. When these nuclei cease their state of inhibition (i.e., are "disinhibited"), they become spontaneously active and cause excessive spastic tone in the involved muscles, as we discuss more fully later in the chapter. This is the spasticity that normally accompanies a "stroke" in a human being. Damage to this area causes lack of patient's fingers coordination and patient cannot precisely contract just one digit or a particular group of digits. 30 Mustansiriyah College of Medicine Clinical application: The middle cerebral artery supplies the majority of the lateral surface of the cortex, including the section of primary motor cortex (and primary sensory cortex) responsible for movement (and sensation) of the face and upper extremities. An occlusion of the middle cerebral artery will cause contralateral spastic paresis (and impaired sensation) of the face and upper extremities. The area responsible for the lower extremities is supplied by the anterior cerebral artery; an occlusion of the anterior cerebral artery will have similar effects of the lower extremities. The supplementary motor cortex: This is located on medial surface of the frontal lobe slightly anterior to the primary motor cortex. It is responsible for generating mental planning of complex sequence of events of a motor act that need bimanual coordination (for example tying shoe laces) and sends these instructions to the premotor Area. Example: When you try to tie your shoe laces, you may sit down on a chair, then you may bend your back forward, then use your both hands to hold the ends of lace, then stretch the lace firmly, then make a node. Such mental planning of the sequence of events of a motor act is achieved by the supplementary motor cortex. It is important in movements that require both hands e.g. tying one’s shoe laces. Damage to this area leads to the following: Patient cannot tie shoe laces because of impaired selection of a particular movement sequence. The premotor cortex: This is located anterior to primary motor area and below the supplementary motor area on the lateral side of the hemisphere. It assembles the details of the mental planning of a motor act received from the supplementary motor area. In another words, this area instructs the primary motor area of how to do the motor act by constructing the details of the muscles involved in each event of a motor act and arrange the muscle contractions in order. This area is active during “mental rehearsal” for a movement. With repetition, the proper pattern of stimulation becomes stored in your premotor cortex as a ready-made program (also called engram). Damage to premotor cortex area leads to the following:  Patient cannot initiate the movement the patient wishes to make.  Patient exhibits motor apraxia (defect in motor performance without paralysis) because the selection of a particular movement is impaired.  Reappearance of grasping reflex. E.g. when you have a patient in coma and you try to put a thing in his hand, he grasps it. Grasp reflex: happens when you put something the baby's hand, he will just grasp it, and this is before the age of 2 years, normally after 2 years, the area 6 is well developed and this reflex will be inhibited.  Loss of bimanual coordination. Within the premotor cortex the following areas are present: 1. Broca’s area (Brodmann’s area 44 and 45) for speech: This is the ward formation area. In most people (97%), both Broca's area and Wernicke's area are found in only the left hemisphere of the brain. Damage to it (Broca's aphasia or non-fluent aphasia) does not prevent a person from vocalizing, but it does make it impossible for the person to speak whole words rather than uncoordinate utterances or an occasional simple words such as “no” or “yes”. 2. The voluntary eye movement area (Brodmann area 8 & 9) for controlling eye and eyelid movements such as blinking. It is part of the frontal cortex in the human brain. Situated just anterior to the premotor cortex (BA6), it includes the frontal eye fields (so-named because they are believed to play an important role in the control of eye movements). Damage to this area prevents a person from voluntarily moving the eyes toward different objects. Instead, the eyes tend to lock on specific objects, an effect controlled by signals from the occipital region. Damage to this area, by stroke, trauma or infection, causes tonic deviation of the eyes towards the side 31 Mustansiriyah College of Medicine of the injury. This finding occurs during the first few hours of an acute event such as cerebrovascular infarct (stroke) or hemorrhage (bleeding).This area also controls eyelid movements such as blinking. 3. Head rotation area: Stimulation this area will elicit head rotation. This area is closely associated with the eye movement field and presumably related to directing the head toward different objects. 4. Area for hand skills: Damage to this area causes the hand movements become incoordinate and nonpurposeful, a condition called motor apraxia. B: Pyramidal tract (corticospinal and corticobulbar tracts): This tract originates from Giant pyramidal cells or Betz cells in primary motor cortex (area 4). Some fibers originated from premotor cortex and supplementary motor areas and from the somatic sensory areas at the parietal lobe.  30% of pyramidal fibers arise from primary motor area (area 4) and supplementary motor areas  30% from premotor area (area 6)  40% of fibers arise from somatosensory areas. The pyramidal tracts include both the corticospinal and corticobulbar tracts (go to the motor nuclei of cranial nerves III, IV, V, VI, VII, IX, XI, and XII, in many cases bilaterally). These upper motor neuron nerve fibers travel from the cerebral cortex and terminate either in the brainstem (corticobulbar) or spinal cord (corticospinal) and are involved in control of motor functions of the body. Through their travel, they send collateral fibers to many subcortical structures. The afferent nerve fibers that travel from the somatic sensory cortex are terminated at sensory cell groups in the dorsal horn of the spinal cord and in the dorsal column nuclei to keep them at a certain degree of excitation or inhibition thus helping to control the faithfulness of sensory signal transmission from incoming somatosensory pathways. This is achieved by controlling the amount of information being passed on to the brain and probably they instruct the sensory nuclei at the spinal cord that a movement is about to take place. Regardless of the location of their cell bodies, pyramidal tract fibers (corticospinal tract) begin their descent from the cortex as a corona radiata (radiating crown) before forming the internal capsule. At the level of medulla, the majority of the pyramidal fibers (80%, originated mainly from primary motor area) then crosses to the opposite side and descends in the lateral corticospinal tracts of the cord. Finally, these fibers terminate either directly or indirectly through interneuron (excitatory for the agonist muscles or inhibitory for antagonist muscles) that in turn synapse with anterior motor neurons. These fibers are concerned with contralateral distal limb muscles and hence with skilled movements especially of the hands and fingers. The pyramidal tract is a major controller of muscle activity for finger movements for performance of voluntary, purposeful activity such as writing, typing, tying knots, fastening buttons and playing musical instruments. However, some of the fibers terminate directly on the anterior motor neurons. A few of the fibers (20%, originated mainly from premotor area) do not cross to the opposite side in medulla but pass ipsilaterally down the cord through the reticular formation as ventral (anterior) corticospinal tracts, but before termination, majority of the fibers of this anterior corticospinal tract cross to the opposite side at different levels of spinal cord either directly or through interneurons to synapse with anterior motor neurons. These fibers are concerned with axial and proximal limb (girdle) muscle contraction. The neurotransmitter of the pyramidal system is glutamate and/or aspartate. 32 Mustansiriyah College of Medicine The cerebral cortex itself and subcortical structures (basal ganglia, brainstem reticular formation, Olive, Red nucleus, and cerebellum) all receive simultaneously strong signals from the pyramidal tract every time a signal is transmitted down the spinal cord to cause a motor activity. A highly selective damage to lateral corticospinal tract is associated with deficit with fine skilled movements of hand and fingers. On the other hand, lesion of ventral corticospinal tract causes difficulty with balance, walking, and climbing. Clinical application: Poliomyelitis and amyotrophic lateral sclerosis (ALS) are two diseases that involve destruction of motor neurons. In both diseases, the skeletal muscles atrophy from lack of innervation. Poliomyelitis is caused by the poliovirus, which destroys motor neurons in the brainstem and ventral horn of the spinal cord. ALS is also known as Lou Gehrig disease after the baseball player who contracted it. It is marked not only by the degeneration of motor neurons and atrophy of the muscles, but also sclerosis of the lateral regions of the spinal cord—hence its name. In most cases of ALS, neurons are destroyed by an inability of astrocytes to reabsorb glutamate from the tissue fluid, allowing this neurotransmitter to accumulate to a toxic level. The early signs of ALS include muscular weakness and difficulty in speaking, swallowing, and using the hands. Sensory and intellectual functions remain unaffected, as evidenced by the accomplishments of astrophysicist and best-selling author Stephen Hawking, who was stricken with ALS while he was in college. Despite near-total paralysis, he remains highly productive and communicates with the aid of a speech synthesizer and computer. Tragically, many people are quick to assume that those who have lost most of their ability to communicate their ideas and feelings have no ideas and feelings to communicate. To a victim, this may be more unbearable than the loss of motor function itself. The extrapyramidal system: Which includes all those portions of the brain and brain stem and their fibers that contribute to motor control but that are not part of the pyramidal system. This system is concerned mainly with:  Postural control and stability,  Inhibits unwanted muscular activity,  Maintains muscle tone,  It is responsible for facial expression such as sadness, irony and happiness and swallowing. Extrapyramidal system includes: 1. Basal ganglia, 2. Reticular formation, 3. Vestibular nuclei, 4. Red nuclei, 5. Tectum (superior colliculi), 6. Olivary nucleus, 7. Cerebellum. The descending spinal extrapyramidal tracts 33 Mustansiriyah College of Medicine are crossed lateral pathway except vestibular nucleus which has in addition crossed and uncrossed ventromedial pathways to the cervical segments of the spinal cord. The main spinal extrapyramidal tracts (indirect corticospinal tract) include:  Tectospinal tract (from the superior colliculus of the tectum and is involved in the control contralateral neck muscles),  Vestibulospinal tract (from vestibular nuclei),  Reticulospinal tracts (from pontine and medullary reticular formation),  Rubrospinal tract (from the red nucleus). The extrapyramidal system serves an essential function in maintaining posture and regulating involuntary motor functions, in particular, the EPS provides:  Postural tone adjustment  Preparation of predisposing tonic attitudes for involuntary movements  Performing movements that make voluntary movements more natural and correct  Control of automatic modifications of tone and movements  Control of the reflexes that accompany the responses to affective and attentive situations (reactions)  Control of the movements originally voluntary then become automatic through exercise and learning (e.g., in writing)  Inhibition of involuntary movements (hyperkinesias), which are particularly evident in extrapyramidal diseases. The red nucleus: A distinctive oval nucleus (pink in fresh specimens because of an iron-containing, hemoglobin and ferritin pigment in many of the cells). It centrally placed in the upper mesencephalic reticular formation of the brain stem in the tegmentum of the midbrain next to the substantia nigra. It comprises caudal magnocellular and rostral parvocellular components. It receives fibers from the cerebellum, cerebral cortex, and from basal ganglia and the most important efferent projection of the red nucleus is to the contralateral spinal cord. It operates in close association with the pyramidal tract. This nucleus gives rise the rubrospinal tract that crosses to the opposite side in the lower brain stem and follows a course parallel to the lateral corticospinal tract and terminate indirectly (through interneuron) on the anterior motor neurons. The red nucleus has a somatotopical representation of all the muscle of the body similar to the motor cortex but far less developed fineness of representation. The corticorubral pathway serves as an acces

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