Motor systems. Motor systems

Transcription

1 515 The control of voluntary movements is extremely complex. Many different systems across numerous brain areas need to work together to ensure proper motor control. We will start a journey through these areas, beginning at the spinal cord and progressing up the brain stem and eventually reaching the cerebral cortex. Then to complete the picture we ll add two side loops, the basal ganglia and the cerebellum. This is relatively DIFFICULT MATERIAL because our understanding of the nervous system decreases as we move up to higher CNS structures. It is EXTREMELY IMPORTANT TO COMPLETE ALL OF THE PRACTICE QUESTIONS. Please KEEP UP and you will really enjoy this section. Get behind and you will NOT! Remember, this material is extremely important for you as future physicians, because many of your patients will exhibit signs and symptoms associated with motor diseases and an understanding of the underlying mechanisms presented here is essential. SPINAL LOWER MOTOR NEURONS Lower motor neurons (LMNs; also called alpha motor neurons), are directly responsible for generation of force by the muscles they innervate. A motor unit is a single LMN and all of the muscle fibers it innervates. The collection of LMNs that innervate a single muscle (triceps) is called a motor neuron pool. LMNs respond to, and are therefore controlled by, inputs from three sources, dorsal root ganglia, interneurons (cells that do not project out of the area), and projections from higher centers such as the brain stem and cerebral cortex. You should remember from the spinal cord and brain stem module that LMNs that control proximal and distal muscles are found mainly in the cervical and lumbosacral segments of the spinal cord. At these levels, the LMNs are distributed such that neurons controlling axial muscles lie medial to those LMNs controlling distal muscles and motor neurons controlling flexors lie dorsal to those controlling extensors. In the thoracic cord below T1, the LMNs are associated only with axial musculature.

2 516 Dorsal Root Inputs to LMNs Stretch reflexes work to resist lengthening of a muscle. They are functionally efficient because they allow weight-bearing muscles to adjust to a changing load at the level of the spinal cord, without the information having to go all the way up to cortex for a decision. You should recall the Ia and II fibers in the dorsal roots. Ia fibers are associated mainly with the nuclear bag intrafusal fibers and carry information regarding the length and change in length of the muscle. The II fibers are primarily concerned with the constant length of the muscle and thus bring information into the spinal cord from the nuclear chain fibers. These fibers are important in stretch reflexes. Stretch of the intrafusal muscle fibers results in contraction of the extrafusal muscle fibers in the same (homonymous) muscle. This is a monosynaptic reflex, in that there is only one synapse between the incoming information and the outgoing signal to contract the muscle. (It has been shown that this monosynaptic reflex takes about 1 ms; the synaptic delay between the sensory input and the LMN is between 0.5 and 0.9 msec). In the cat, a single 1a fiber makes excitatory connections with all homonymous motor neurons. This Ia divergent signal produces a very strong excitatory drive to the muscle within which it originates. This is called autogenic excitation. The Ia fiber also makes monosynaptic connections with LMNs that innervate muscles that are synergistic to the homonynous muscle. The incoming Ia fiber also synapses on a Ia inhibitory interneuron that in turn inhibits LMNs that innervate the antagonist muscles (stretch biceps contract biceps inhibit triceps; notice this is NOT a monosynaptic reflex). This is called reciprocal innervation. Ia inhibitory interneurons are also important for coordinating voluntary movements, as corticospinal axons make direct excitatory connections with LMNs and also send a collateral to the Ia inhibitory neuron. Thus, the cortex does not have to send separate messages to the opposing muscles. The intrafusal muscle fibers can be controlled by the small gamma efferent neurons that lie in the ventral horn. These gamma efferent cells, which are controlled by descending inputs, bias the intrafusal muscle fibers in order to ensure that the intrafusal muscle fibers are always signaling information to the brain. For instance, contraction/shortening of the extrafusal muscle will put slack on the intrafusal fibers, and they will stop telling the brain about the length of the muscles. This is

3 517 bad! To get around this, the cortical input tells the gamma efferents to fire and tighten up the intrafusal muscle fibers (to keep them firing) when the extrafusal fibers contract. The gamma efferents that innervate the bags are called gamma dynamics while those targeting the chains are gamma statics. Inverse Stretch (myotatic) Reflex The Ib fibers are carrying information from Golgi tendon organs (GTOs; Dr. Royce used to drive a 68). Each GTO is comprised of collagen fibers intertwined with a Ib fiber. Thus, stretching of the tendon squeezes the Ib fiber and it begins to fire. While muscle spindles are sensitive to changes in length of a muscle, GTOs are most sensitive to changes in muscle tension and thus signal the force in a muscle. GTOs provide the nervous system with precise information about the state of contraction of the muscle. The inverse stretch reflex is also known as the inverse myotatic reflex or Golgi tendon reflex. This reflex involves Ib afferents, Ib inhibitory interneurons, and LMNs. Thus, increased firing of the Ib results in the inhibition of the homonymous muscle (autogenic inhibition).

4 518 The inverse stretch reflex is polysynaptic, meaning that it involves more than one synapse. This reflex is therefore slower than the stretch reflex. However, the inverse stretch reflex can override the stretch reflex, and serves two important functions. The first function is protective. If there is a very large stimulus, such as a strong blow to the patella tendon with a hammer, the quadriceps muscles will contract due to the stretch reflex. To prevent damage to the tendon due to the muscle pulling too hard on it, the inverse stretch reflex is initiated by increasing tension in the tendon, and the contraction of the muscle is inhibited. The inverse stretch reflex is therefore damping down the effect of the stretch reflex. Flexion/withdrawal reflex Pain and temperature fibers in the dorsal roots (Cs and deltas) play a role in the flexion reflex, also known as the withdrawal reflex (you already know the pathway over which this pain and temperature information reaches cortex via the ALS etc). At the spinal level, this reflex responds to noxious stimuli, such as a hot object on the skin. The result is a rapid flexion that confers a protective mechanism against damage by the stimulus. Another example of this reflex is stepping on a pin. The pin will be sensed by delta and C fibers, which synapse with a series of excitatory and inhibitory interneurons to produce a flexion response. The excitatory interneurons excite LMNs to the hamstring, while the inhibitory interneurons inhibit LMNs to the quadriceps (reciprocal inhibition).

5 519 The flexion reflex is often accompanied by a crossed extension reflex acting on the contralateral limb. Using the example of stepping on a hot match, the crossed extension reflex would brace the other leg, helping to maintain balance. In this case, excitatory interneurons excite LMNs innervating the quadriceps, while inhibitory interneurons inhibit LMNs that project to the hamstrings. You can see from the flexion/crossed extensor reflex that flexion withdrawal is a complete, albeit simple, motor act. While this reflex is reasonably stereotyped, the spatial extent and force of muscle contraction is dependent upon stimulus intensity. For instance, a moderately painful stimulus will result in the production of a moderately fast withdrawal of your finger and wrist, while a real painful stimulus results in the forceful withdrawal of the entire limb. Thus reflexes are not simply repetitions of a stereotyped movement pattern, but instead are modulated by the properties of the stimulus. It is important to understand that reflexes are adaptable and control movements in a purposeful manner. For example, a perturbation (a disturbance of motion, course, arrangement, or state of equilibrium) of the left arm can cause contraction of the opposite elbow extensor in one situation (opposite arm used to prevent the body from being pulled forward) but not the other, where the opposite arm holds a cup and the perturbation causes an inhibition of opposite elbow extensor. Also, don t forget that spinal reflexes are functionally efficient because they enable adjustments of movements to be made at the level of the spinal cord, without having to involve (and wait for) decisions from higher levels of the motor systems.

6 520 SPINAL CORD NEURONAL NETWORKS (CENTRAL PATTERN GENERATORS) Hopefully you now understand some basic reflexes involving the LMNs. Let s move up slightly in the motor hierarchy, and in particular, to neuronal networks in the spinal cord that generate rhythmic alternating activity. A central pattern generator (CPG) is a neuronal network capable of generating a rhythmic pattern of motor activity. Normally, these CPGs are controlled by higher centers in the brain stem and cortex. A simple spinal cord circuit is shown below and to the right. This circuitry underlies alternating flexion and extension because when some cells are active the others are inhibited. These cells lie in the ventral horn on the same side of the spinal cord and include flexor and extensor motor neurons, together with their associated interneurons. Descending inputs from higher levels provide continuous input to the excitatory interneurons. However, because of random fluctuations in excitability or other inputs, one half-center initially dominates and inhibits the other. Let s say for example that excitatory interneuron #1 turns on first. It will not only excite the flexor LMN and cause flexion, but it will also turn on inhibitory interneuron #2, which inhibits excitatory interneuron #2 so that the extensor LMN is inhibited. Inhibitory interneuron #2 also inhibits itself, so the flexion will switch to extension when the inhibitory interneuron #2 stops firing. Remember, the tonic inputs are exciting excitatory neuron #2. This will mean that now the excitatory interneuron #2 will fire and excite inhibitory interneuron #1. You do not have to understand any of the details of such circuits. What you need to know is that there are groups of cells in the spinal cord, both LMNs and interneurons, which generate basic patterns of locomotion. Sometimes these CPGs can be activated below the level of a spinal cord transection. For instance, if a quadriplegic s hips are extended, spontaneous uncontrollable rhythmic movements (flexion and extension) of the legs occur. Moreover, if babies are held erect and moved over a horizontal surface, rhythmic stepping movements take place. Granted, these stepping rhythmic activities in babies involve sensory input, but the circuitry for the rhythmicity of the movements is in the spinal cord. These two examples indicate that basic neuronal circuitry for locomotion is established genetically.

7 521 Practice Questions 1. Which of the following statements is TRUE? A. LMNs innervating axial muscles lie laterally in the spinal cord ventral horn B. LMNs innervating distal flexors are present at all levels of the spinal cord ventral horn C. LMNs innervating extensors lie dorsal to those innervating flexors in the spinal cord ventral horn D. LMNs innervating distal muscles lie lateral to those innervating axial muscles in the spinal cord ventral horn E. a motor neuron pool is a LMN and all of the muscle fibers it innervates 2. Which of the following is monosynaptic? A. crossed extensor reflex B. flexor reflex C. inverse myotatic reflex D. stretch reflex involving agonist muscle E. stretch reflex involving inhibition of antagonist muscle 3. Which of the following statements about gamma efferents is TRUE? A. they innervate extrafusal muscle fibers B. stimulation of dynamics causes shortening of the chain fibers C. are controlled by descending inputs D gamma dynamic stimulation leads to a pause of Ia firing during contraction/shortening E. control GTOs 4. Which of the following statements is TRUE? A. basic patterns of locomotion can only be accomplished via cortical involvement B. a quadraplegic is incapable of any rhythmic movement C the basic neuronal circuitry for locomotion is established genetically D. Ib fibers that are involved in the inverse myotatic reflex directly inhibit LMNs innervating the muscle that is attached to the tendon/gto innervated by the Ib fiber E. when you step on a tack, you activate ipsilateral extensors and contralateral flexors

8 Which of the following statements is TRUE? A. reciprocal innervation is excitation of groups of LMNs that innervate muscles with opposing actions B. Ib fibers synapse upon Ia excitatory interneurons C. autogenic excitation is associated with Ia fibers D. autogenic inhibition is associated with Ia fibers E. Ia fibers synapse upon Ia excitatory interneurons 6. Which of the following associations is TRUE? A. B = excitatory; B. A = inhibitory; C. C = increase in firing; D. D = decrease in firing; E. E = alpha-beta Answers 1. D. 2. D 3. C 4. C 5. C 6. D

9 523 INFLUENCE OF HIGHER CENTERS UPON LMNS At this point in our examination of the motor systems we know that there is reflex and central pattern program circuitry within the spinal cord and that certain reflexes and movements can occur using this intrinsic circuitry of the spinal cord. The next level of organization in the motor systems hierarchy includes descending inputs to the spinal cord circuitry from a number of different nuclei in the brain stem and primary motor cortex. Descending pathways to the spinal cord can be divided into ventromedial and dorsolateral systems based upon which spinal cord funiculus the pathway travels in and the termination pattern of its axons in the spinal cord grey. Ventromedial system control of axial and proximal musculature You already know that the tecto- and vestibulospinal tracts (MVST and LVST) travel in the ventral funiculus and terminate on LMNs that control axial and proximal musculature. Thus, they keep the head balanced on the shoulders as the body navigates through space, and the head turns in response to new sensory stimuli. The pontine and medullary reticulospinal tracts (PRST and MRST) also travel in the ventral funiculus. (These pathways were not presented in the spinal cord and brain stem lectures, so you have not forgotten them). The PRST, which lies medial to the MRST in the ventral funiculus, arises from cells in the pons that lie around and near the PPRF (paramedian pontine reticular formation at the level of the abducens nucleus and motor VII; level 5). In contrast, the MRST has its origin from cells dorsal to the inferior olive (level 3). The reticular formation consists of those cells in the brain stem that do not comprise the sensory and motor nuclei that you so carefully learned earlier in the course.

10 524 The PRST enhances the anti-gravity reflexes of the spinal cord. Thus, this pathway excites upper limb flexors and lower limb extensors. This is an important component of motor control, since most of the time the activity of ventral horn cells maintains, rather than changes, muscle length and tension. PRST cells are spontaneously active but they also receive excitatory input from the cerebellum (soon to be discussed) and the cortex The MRST has the opposite effect of the PRST, in that it inhibits anti-gravity reflexes of spinal cord (inhibits upper limb flexors and lower limb extensors). MRST cells, like those in the PRST also receive excitatory input from the cerebellum (soon to be discussed) and the cortex. All of these ventromedial pathways (MVST, LVST, TST, MRST, PRST) innervate LMNs and interneurons that innervate axial and proximal limb muscles. Moreover, the axons in the ventromedial pathway distribute collaterals to many segments along their distribution in the spinal cord (for the coordination of intersegmental movements). You can see that such a distribution is not well suited for the discrete control of a few muscles but rather for control of groups of muscles involved in posture and balance. Lesions of the ventromedial pathways in animals result in difficulty in righting to a sitting or standing position and immobility of the body axis and proximal parts of the extremities. However, the hands and distal parts of the extremities are still active. Thus, descending pathways controlling LMNs that innervate these more distal muscles must not travel in the ventromedial part of the spinal cord.

11 525 Dorsolateral system control of distal musculature You already know about the lateral corticospinal tract (LCST), and this is one of the two dorsolateral pathways. This pathway is especially important for the control of distal musculature and for steering extremities and manipulating the environment. The other pathway in the dorsolateral system is the rubrospinal tract (RST), which arises from our old friend the ruber-duber. Both of these pathways course within the lateral funiculus and are important for the control of distal limb musculature. It should not come as a surprise that axons of the dorsolateral system terminate at only one or two segments (in contrast to the more extensive distribution of ventromedial axons) and reach the LMNs that lie more laterally in the ventral horn. Thus these pathways are involved in the finer motor control of the distal musculature (finger movements for example). Lesions involving both dorsolateral pathways result in the inability to make fractionated (independent) movements of the wrist or fingers. Moreover, voluntary movements are slower and less accurate, however, the patient still has the ability to sit upright, and stand with relatively normal posture (via functioning pathways in the ventromedial system). A lesion of only the LCST initially resembles the combined lesion involving the LCST and the RST, but after a while the main deficit is that there is weakness of the distal flexors and the inability to move the fingers independently (fractionated movements). Evidently, the functioning RST accounts for the recovered function of the wrist. Practice Questions 1. Which of the following statements is TRUE? A. pathways in the ventromedial system are functionally related to the control of the distal muscles B. pathways in the dorsomedial system are functionally related to the control of axial and proximal muscles C. the rubrospinal tract is part of the dorsolateral pathway D. the PRST is part of the dorsolateral system system E. following a lesion of the ventromedial pathway, there would be atrophy of the axial and proximal musculature 2. Which of the following statements regarding the dorsolateral pathway is TRUE? A. lesions result in the inability to control the distal musculature B. it would be easy to button a shirt/blouse C. contains the pontine and medullary reticulospinal tracts D. contains the lateral vestibulospinal tract E. terminates in the more medial parts of the spinal cord grey

12 Which of the following statements regarding the pontine reticulospinal tract (PRST) is TRUE? A. inhibits the quadriceps B. excites flexors in the arms C. courses within the lateral funiculus D. is functionally associated with the ruber-duber E. lesion would result in atrophy of interosseous muscles 4. Which of the following statements regarding the medullary reticulospinal tract (MRST) is TRUE? A lies in the rostral brain stem B. excites antigravity muscles (flexors in the arms and extensors in the legs) C. courses within the lateral funiculus D. is functionally associated with the corticospinal tract E. inhibits antigravity muscles (flexors in the arms and extensors in the legs) 5. Which of the following is polysynaptic? A. crossed extensor reflex B. flexor reflex C. inverse myotatic reflex D. stretch reflex involving inhibition of antagonist muscle (reciprocal innervation) E. all of the above are TRUE Answers 1. C 2. A 3. B 4. E 5. E

13 527 PRIMARY MOTOR CORTEX: EXECUTION OF MOVEMENTS Now we are up there in the motor cortex. Pretty far from those lowly grunts the LMNs, and those slightly more intelligent CPGs and those pathways in the ventromedial system. The primary motor cortex is also called area 4 of Brodmann and motor I (MI). Corticospinal cells in area 4 project directly to the lower motor neurons (LMNs) in the spinal cord and brain stem and tell these LMNs, and in turn the muscles they innervate, what to do. They are the classic upper motor neurons (UMNs). MI is located in the precentral gyrus, which lies in front (rostral) of the central sulcus. MI occupies most of this gyrus along both its lateral and medial surfaces and is bound caudally by the central sulcus. Left: Human motor map in a coronal or frontal section through area 4 or MI. The entire lateral surface of the right hemisphere is seen while only the dorsal and medial aspect of the left hemisphere is visible. Right: The map of the body (homunculus) as represented on the precentral gyrus. Medial is to the left, lateral to the right. Somatotopic organization of MI In the late 1950s Wilder Penfield studied the somatotopic organization of MI in patients by stimulating MI with relatively large electrodes (the patients gave their permission to do this as part of their surgery). He found a topographically organized representation of the entire head and body, which is schematically shown above and to the right as the classic homunculus (little man or person). The head and forelimbs are represented laterally, and the hind limb and feet medially. The cortical areas allotted to different bodily regions are of unequal size, with the degree of representation proportional to the amount of skilled movement that is required of the respective part of the body. Thus, in humans the face (particularly the tongue and lips used in speaking), thumb, and hand receive a disproportionate representation, giving these structures a correspondingly exaggerated appearance. Movements of limbs evoked by stimulation of MI are strictly contralateral, but movements of the face (remember corticobulbars) may be bilateral.

14 528 The main outputs of MI are the now familiar corticospinal and corticobulbar pathways, which arise from cells that are pyramidal in shape and lie in layer 5 of MI (most of the cerebral cortex has 6 layers, 1 being most superficial and 6 the deepest). The largest corticospinal cells are called Betz cells. Several corticospinal axons are shown in the drawing above as they course through the posterior limb of the internal capsule, the cerebral peduncle, pyramids of the medulla and pyramidal decussation. Once in the spinal cord, these corticospinal axons comprise the LCST. You will learn more about the internal capsule in a future lecture. For now, all you need to know is that it is 1) a large fiber bundle that contains axons going to and coming from the cerebral cortex, 2) that it has an anterior and posterior limb separated by a genu (bend or knee) and 3) that the corticospinal tract axons course through the posterior limb, while the corticobulbars are found in the genu.

15 529 The experimental setup for recording from MI neurons in a monkey trained to move a lever to the right or left. Weight can be added to resist or assist flexion or extension by attaching a weight to the lever and placing the line over the left or right pulley. Physiology of corticospinal meurons Much of what we know about the physiology of cells that project into the corticospinal tract comes from single neuron recordings in awake monkeys trained to perform specific tasks. Since corticospinal neurons course within the pyramids when they are in the medulla, they are also called pyramidal tract neurons (PTNs). If a monkey is trained to move a handle by flexing and extending the wrist, then the PTNs can be studied. In the experiment shown above, a light comes on to signal to the monkey that he/she should either flex or extend their wrist. It takes a while for the brain to get the visual information (the light signal) to MI before the PTN will begin to fire. There are PTNs related to either flexion or extension of the wrist and the ones that fire depend on the light signal. If the light signal is a cue to flex, the PTNs involved in flexion will fire and send information down the corticospinal tract to the level of the medulla where the pathway decussates. The lateral corticospinal tract then continues to the LMNs in the ventral horn that innervate either the extensors or flexors of the wrist.

16 530 Trace A below shows the activity of PTNs recorded with a microelectrode placed into MI. Each vertical line, or spike, represents an action potential, with spikes of similar sizes coming from a single neuron. (Note that there were 2 neurons recorded in this series, one with large spikes, and another with smaller potentials). Trace B shows the electromyographic (EMG) activity of the wrist flexor muscle related to the task, and trace C indicates the time during which the lever is moved. Note the timing relationship between the discharge of PTNs, the EMG activity of the muscle, and the actual movement of the limb. As mentioned earlier, the PTN response always precedes the EMG activity, as expected since it is producing the motor command for that movement. Moreover, the same neuronal activity is seen even when the movement is done repeatedly many hundreds of times each day (i.e., there is no adaptation or habituation of the activity). The response of a wrist flexor PTN during flexion of the wrist with no load. Note how the cell fires before the muscles start to contract. Also notice that the muscles start to contract before the lever actually moves. Functions of MI Recent studies have shown that corticospinal cells are telling LMNs in the spinal cord what to do. In fact, corticospinal cells are involved in conveying a lot of details about amplitude, force and direction to the LMN. In other words, MI neurons are NOT leaving these decisions up to the LMNs, as they are too dumb. Thus, MI cells tell the LMNs (and in turn the muscles) what direction to move, how far to move (amplitude) and how much force to use. The corticospinals in MI are specifying some pretty basic stuff instead of just sitting back and saying grab that glass of water, arm and hand and leaving the rest of the work to the poor LMNs. Remember, MI s contributions to motor control include controlling the number of muscles and movement forces and trajectories. MI cells are mainly concerned with the actual execution of the movements.

17 531 Effects of lesions of MI In general, with lesions of MI there will be the usual constellation of signs associated with UMN lesions. There will be hemiplegia that is especially noticeable for voluntary movements of the distal extremities. Also a Babinski sign would be present if the lesion involves UMNs of the lower limb. Remember that skilled, independent movements of the distal extremities (fingers) are most affected. The rubrospinal tract (which along with the corticospinal tract is a component of the dorsolateral system) can help carry out some of its more distal (wrist) limb movement tasks but isn t much help when it comes to the more refined movements of the fingers). Also, recall that the ventromedial system is functioning and thus the axial and more proximal muscles are able to function. Blood Supply of MI Area 4 or MI receives its blood supply from the Middle Cerebral Artery and Anterior Cerebral Artery. Note that the anterior cerebral artery feeds the part of MI that controls the lower limbs, while the middle cerebral artery feeds the upper limb and head portions of MI. AFFECTED ARTERY AREA AFFECTED SIDE Ant. Cerebral Lower limb Contra Mid. Cerebral Upper limb and Head Contra Table 1. Relationship of Injured Artery and Resulting UMN Deficit

18 532 Practice Questions 1. Which of the following statements is TRUE regarding primary motor cortex (MI)? A. lies in the precentral gyrus B. contains corticospinal or pyramidal tract neurons C. is found in Brodmann s area 4 D. is supplied in part by the anterior cerebral artery E. all of the above are TRUE 2. Which of the following statements is TRUE regarding primary motor cortex (MI)? A. head representation is lateral to that of the upper limb B. complete occlusion or rupture of the left anterior cerebral artery near the Circle of Willis will result in an upper motor neuron (UMN) syndrome in the left leg C. contains cells that fire following contralateral movements D. supplied only by the middle cerebral artery E. is the same as area 6 3. Which of the following statements is TRUE? A. a lesion of MI results in hemiplegia of the ipsilateral distal extremity muscles B. the largest corticospinal neurons in area 4 are called Betz cells C. there is considerable muscle atrophy associated with lesions of the corticospinal/lcst D. the inverse myotatic reflex involves Ia excitatory interneurons E. autogenic excitation is functionally associated with GTOs 4. Which of the following statements is TRUE? A. circuits for basic patterns of locomotion are found only in the motor cortex B. the lateral corticospinal tract (LCST) is part of the ventromedial system C. LMNs innervating axial muscles lie medially in the spinal cord ventral horn D. when you step on a tack, you activate ipsilateral extensors and contralateral flexors E. gamma efferents innervate extrafusal muscle fibers

19 Which of the following statements is TRUE? A. there is a greater representation of the big toe in MI than the lip B. the lip representation lies near the lateral fissure in MI C. gamma efferents control GTOs D. pontine reticulospinal tract (PRST) fibers inhibit antigravity muscles (flexors in the arms and extensors in the legs) E. the MRST travels in the lateral funiculus 6. Which of the following statements is TRUE? A. the key word that reflects the function of MI is execution B. a motor neuron pool is all of the muscle fibers innervated by a single LMN C. Betz cells are the smallest corticospinal neurons D. a motor unit is all of the LMNs that project to a muscle E. the ruber-duber is associated with the ventromedial system Answers 1. E 2. A 3. B 4. C 5. B 6. A

20 534 MOTOR ASSOCIATION/PREMOTOR CORTICAL AREAS The primary motor cortex (MI; area 4) was the first motor cortical area discovered. It takes relatively little stimulating current of this cortical area to evoke a movement. This is because the corticospinal neurons that lie in MI are directly connected to the LMNs in the brain stem and spinal cord. Movements also result from stimulation of other areas of cortex that lie immediately rostral to MI, and we call these motor association areas (supplementary motor area and lateral premotor area on the drawing below). Since these motor association areas influence LMNs primarily via their inputs to MI corticospinal cells, more current is needed to evoke movements. Premotor areas tell MI what movements to execute. That is, they are involved with the planning of a movement. The total size of these premotor areas is considerably larger than area 4, and thus these areas prove to be particularly important in the control of human voluntary movement and are often compromised in diseases. The two premotor areas we will talk about are the supplementary motor area and the lateral premotor area. Remember, both are part of area 6. Lateral premotor area The lateral premotor area (PMl) lies on the lateral convexity of the hemisphere. (This same area has also been called the dorsal and ventral premotor cortex but let s use PMl). Many motor actions are often responses to visual or auditory cues, and cells in PMl are active during such externally cued movements. For instance, you see an apple (external cue) and the apple cues a movement to reach out and grasp it. The pathways involved in this sensorimotor transformation (seeing it is sensory and reaching for and grasping it is motor ) are seen in the adjacent drawing. The visual information (apple) falls first on the retina, and the retinal signal eventually reaches the primary visual cortex in the back of the brain (area 17). From area 17, the retinal information is conveyed rostrally and bilaterally to what is termed the posterior parietal cortex (areas 5 and 7 or just call it PPC). The PPC helps to transform visual information about the location of the apple in extrapersonal space into the direction of a reaching movement (moving a body part relative to another body part is an example of a movement in intrapersonal space, while movements in extrapersonal space are movements executed in a three dimensional coordinate system fixed by points in the environment whew!). Information from PPC is conveyed to PMl. PMl projects bilaterally to another premotor area called the supplemantary motor area (SMA). The SMA contralateral to the apple then turns on MI to execute the reaching movement.

21 535 Lesions of the PMl result in apraxia, which is an inability to perform a purposeful movement (especially skilled) in the absence of any significant paralysis, sensory loss, or deficit in comprehension. For example, monkeys can be trained to turn or pull a handle (MI is OK) depending upon whether the handle is red or blue. If there is a lesion of PMl, the monkey can still turn and pull the handle, but they can not learn to associate the correct movement with the correct external visual cue (colors). That is, the monkey s deficit lies in finding that particular movement when they are presented with a particular cue. Supplementary motor cortex The SMA is located immediately rostral to area 4, and includes the caudal one-third of the medial, dorsal, and lateral surfaces of the superior frontal gyrus. The SMA is involved in the programming of all movement sequences. Thus, it will be active when reaching for the apple. The reaching movement needs to be seqeunced by the SMAs (both sides are active) after the PPC gives the SMA the proper coordinates in extrapersonal space. The SMAs are involved in internally generated movements so, if you suddenly have the internal need to reach out and grab something in front of you (this is NOT precipitated by an external cue), the memory/motor patterns necessary for this movement are encoded in cells within the SMA. Cells in the SMA will start to fire and, in turn, send the instructions for the movement to the workhorse, MI, so that the right muscles are moved with the correct amount of force and speed (execution of the movement). Interestingly, the two SMAs are interconnected by cortico-cortical fibers, and, unlike cells in MI, the activity in the SMA is usually bilateral. So, during the movement of the right arm/hand, cells in both SMAs start firing, but only cells in the left MI fire. Cells in SMA fire before those in MI but both areas will be firing during the movement. Interestingly, if you just imagine reaching out and grabbing something in front of you, cells in SMA will increase firing (bilaterally).

22 536 Monkeys with lesions of SMA have impaired ability to carry out a motor act that they had learned earlier, i.e., apraxia. There is NO paralysis, only problems in planning. For instance, monkeys who had learned how to open a latch box by opening three different latches in a particular sequence are greatly impaired following either uni- or bilateral lesions of SMA. Remember, the two SMAs are interconnected across the midline. A lesion of one affects the proper functioning of the other. For instance, a lesion of the right SMA means the right MI is not getting proper planning information. This affects the left arm/hand. In addition, the left SMA has lost its input from the right SMA so the left SMA input to the left MI is not normal. In the end, bimanual coordination is affected. So, SMA=bimanual coordination. The role of the SMA in sequencing of movements is further exemplified by data from experiments in which monkeys were trained to do three movements; push, pull or turn a manipulandum (a joystick like you use with video games) in four different orders (e.g. push, turn, pull, would be one choice). Cells were found that increased their firing to a particular sequence (turn, push, pull but NOT turn, push, turn). So, SMA is big on sequencing and especially internally or memory-guided movements. Remember, in the above task with the manipulandum, the appearance (an external cue) of the apparatus gave no clue as to which movement to make first, or even the order of the movements. You can see that planning premotor areas are more specialized than the execution cells in MI and are important for selecting and controlling movements made in particular behavioral contexts, such as when the direction of a movement that needs to be made must be remembered (internally generated) or selected on the basis of an available external cue (externally guided). The movement is the same but the areas that activate and tell MI which muscles to turn on (execution) differ. STUDIES OF REGIONAL CEREBRAL BLOOD FLOW Additional information about the activation of cortical areas during different types of movements can be gathered by looking at the regional cerebral blood flow (rcbf) during particular tasks. In these studies an increase in rcbf means the cortical area is active. For example, it has been shown that fast flexions of the index finger against a spring loaded movable cylinder increases rcbf in the finger area of the contralateral

23 537 MI and SI (primary somatosensory area). The increase in rcbf in the somatosensory cortex reflects the activation of peripheral receptors caused by the rapid finger flexions. Most important, no higher cortical motor area exhibited an increase in rcbf in this task. Thus, MI (and its associated LMNs), is the only motor cortical area involved in the control of simple repetitive movements. When a person is asked to carry out from memory more sophisticated and complex movements, then other motor cortical area(s) besides MI exhibit an increase in rcbl. Such a complex movement is where the thumb, in quick succession, must touch the index finger twice, the middle finger once, the ring finger three times, and the little finger two times. Then, with the thumb opposed to the little finger, the whole sequence is reversed!!! This is a complex series of movements guided by memory and carried out in intrapersonal space (moving a body part relative to another body part). Again, there is increased rcbf in the contralateral MI and SI (a bigger area since more fingers are involved), but in addition there is increased rcbf within SMA bilaterally. Thus, a complex task involving a sequence of remembered movements requires the activity of both SMAs and the MI contralateral to the active fingers. Of course, MI is needed for the execution. Interestingly, if you just imagine the finger sequence movement, SMA lights up bilaterally, but not MI. Now, what happens when you are asked to do a complex movement in space such as a memorized spiral movement of the arm and hand? (Someone instructs you as to the specific movements/directions of the spiral and then asks you to close your eyes when you do it). Since this movement is made in extrapersonal space, the posterior parietal cortex (PPC) is needed. In addition to PPC, SMA is active bilaterally because the movement needs sequencing. Of course, contralateral MI is active, as it is doing the labor (execution) and SI is active because it is receiving the sensory information generated by the movement.

24 538 Practice Questions 1. Which of the following statements is TRUE regarding premotor association areas? A. include the lateral premotor (PMl) area and supplementary motor area (SMA), both of which are in Brodmann s area 4 B. lesions result in contralateral paralysis C. thought to be involved in the execution rather than the planning of a movement D. the SMA is partly on the medial wall of the hemisphere E. SMA is supplied entirely by the middle cerebral artery 2. Which of the following statements is TRUE regarding the shaded area shown below? A. a lesion would result in weakness B. a lesion would result in atrophy C. SMA is damaged D. the lesion involves areas 3, 1, 2 E. there is apraxia 3. Which of the following statements is TRUE regarding the shaded area shown below? A. blood supply is predominantly from the anterior cerebral artery B. a lesion here will result in spasticity and paresis only in the contralateral lower limb C. area contains Betz cells D. axons of these cells course through the contralateral pyramid E. lesion would result in apraxia

25 Which of the following statements is TRUE regarding the shaded area shownbelow? A. includes SMA and area 4 B. lateral part is involved in movements based upon externally generated cues C. lateral part of this area will show increased rcbf when imaging a complex sequence of movements D. this area is involved in motor execution and is at a relatively low level in the hierarchy of motor control E. lesions result in an increase in CK in blood 5. Which of the following statements is TRUE regarding the shaded area shown below? A. this is the supplementary motor area and corresponds to Brodmann s area 6 B. is supplied by anterior cerebral artery C. receives input from posterior parietal cortex (PPC) D. cells fire when repeated flexing finger against a spring E. is involved in internally generated movements 6. Which of the following statements is TRUE? A. LMNs innervating extensors lie dorsal to those innervating flexors in the spinal cord ventral horn B. the part of the stretch reflex involving inhibition of antagonist muscles is monosynaptic? C. gamma dynamic stimulation leads to a pause of Ia firing during contraction/shortening D. a part of SMA receives its blood supply from the anterior cerebral artery E. Ib fibers directly inhibit LMNs innervating the muscle that is attached to the tendon/gto innervated by the Ib fiber

26 Which of the following statements is TRUE? A. fibers of cells in MI travel in the ventromedial pathway B. the medullary reticulospinal tract (MRST) excites antigravity muscles C. the pontine reticulospinal tract (PRST) terminates in the lateral parts of the spinal cord grey D. buttoning a shirt button would be possible following a lesion of the dorsolateral system E. MI cells are like the cab dispatcher, while LMNs are like the cab driver (think!!) 8. Which of the following is TRUE? A. apraxia can result from blockage of the anterior cerebral artery B. area 4 is larger than area 6 C. autogenic excitation is associated with the inverse myotatic reflex D. MI is higher in the motor hierarchy than SMA E. autogenic inhibition is associated with the stretch reflex 9. Which of the following associations is TRUE? (the big integrator!) A. LMNs spinal cord, brain stem, input from contralateral MI, input from Ia inhibitory interneurons, input from Ib inhibitory neurons, input from interneurons in contralateral spinal cord, workers instead of planners, ventral=extensors, lateral=distal muscles, some fire during fast flexions of the index finger against a spring loaded movable cylinder, lesion=apraxia B. ventromedial system vestibular nuclei, PRST, MRST, medial spinal cord grey, ventral funiculus, balance and posture, axons innervate many spinal levels, digital dexterity C. dorsolateral system ruber-duber, CST, lateral ventral horn, lateral funiculus, digital dexterity, axons innervate single or limited spinal levels, MVST D. MI force, fires before LMNs, lip area larger than shoulder area, input from SMA, blood supply from anterior and middle cerebrals, area 4, lesion=atrophy E. premotor association areas area 6, PML, SMA, anterior and middle cerebral arteries, project to MI, planning, lesion=apraxia Answers 1. D 2. A 3. C 4. B 5. C 6. D 7. E 8. A 9. E.

27 541 Basal ganglia You have just read about the different motor-related cortical areas. Premotor areas are involved in planning, while MI is involved in execution; corticospinal fibers from MI target LMNs. What you don t know is that the cortical areas involved in movement control need some help from the basal ganglia in order to smoothly orchestrate motor behavior. Without the information from the basal ganglia the cortex is unable to properly direct motor control, and the deficits seen in Parkinson s disease and other movement disorders become apparent. You know that the supplementary motor area (SMA) is involved in the generation of movement sequences. For instance, SMA cells know the overall sequence to be performed, which movement is next according to the sequence, and which movement is currently being performed. One of the most interesting findings in the last few years has been the fact that SMA cells encoding current versus next movements of a sequence use different pathways through the basal ganglia. Before discussing these two different pathways however, we need to look at the various players in the basal ganglia. The adjacent drawings show level 16 of our series of brain sections. Some of the important nuclei and fiber tracts of the basal ganglia can be seen. Two of them are the caudate nucleus (seen only in the top drawing) and the putamen nucleus, which together comprise the striatum. Next to the putamen is the globus pallidus, and it can be seen to have two parts, an external segment (Gpe; also called outer or lateral segment of GP) and an internal segment (GPi; also called inner or medial segment of GP). The putamen and both parts of the globus pallidus, which lie adjacent to each other, together are called the lenticular nucleus (note the lens shape). Finally, the striatum (caudate and putamen) and the globus pallidus are called the corpus striatum.

28 542 You can also see a nice thick fiber bundle associated with the globus pallidus called the ansa lenticularis. This fasciculus passes under (ventral) the posterior limb of the internal capsule. The ansa lenticularis (the jug handle ) then heads rostrally and dorsally to reach the motor thalamic nuclei (VA/VL). The ansa arises from cells of the GPi and terminates in the ipsilateral VA/VL. You should begin to see that the basal ganglia are sending information to the cortex via the thalamus. In addition to the ansa lenticularis, information from the GPi can also reach the thalamus (VA/VL) via the lenticular fasciculus. This is not as simple as the ansa. GPi fibers that make up the lenticular fasiculus pass through (rather than under or ventral) the posterior limb of the internal capsule. We can see the lenticular fasciculus (levels 14 and15) caudal to where we see the ansa (level 16). The fibers in the lenticular fasciculus then pass a little caudally where they lie right on top of a very important motor-related structure called the subthalamic nucleus (level 14). The fibers in the lenticular fasciculus then suddenly loop dorsally and pass rostrally towards the VA/VL (see, this is not as simple as the jug handle ). As the fibers comprising the lenticular fasciculus pass rostrally toward the VA/VL, they join the cerebellothalamic (interpositus and dentate) fibers that are also headed for the VA/VL. These two fiber bundles (lenticular fasciculus and cerebellothalamic fibers) are joined further rostrally by the good ole jug handle (ansa lenticularis) and the three combined form what is referred to as the thalamic fasciculus. Now that we know the various nuclei and tracts of the basal ganglia, we can go back to the SMA and movement sequencing. Remember, SMA neurons contain information about movement sequences and keep track of which movement is currently being performed and which movement is next according to the sequence. Let s consider a sequence with two movements.

29 543 Control of current movement: Direct Pathway through the basal ganglia A SMA cell that contains information about the details of the first movement of a sequence is called SMAmvt1. This cell projects directly to a movement cell in MI called MImvt1. This MImvt1 cell is a corticospinal neuron that tells specific LMNs in the spinal cord and brain stem what to do in order to properly carry out movement 1 of the sequence. In the diagram below, this first movement involves muscles 1, 2, 3. In addition to projecting directly to MImvt1, the same SMAmvt1 cell also sends details regarding the first or current movement into the basal ganglia. The reason this information is going through the basal ganglia is to help the MImvt1 neurons reach their peak firing rate necessary to carry out the movement (move muscles 1, 2,3). That is, the cortico-cortical input from the SMAmvt1 directly to MImvt1 will NOT do it! Help is needed from the basal ganglia in order for MImvt1 to generate enough action potentials to get the job done! So, the loop through the basal ganglia is going to ADD EXCITATION to the MImvt1 cell so that the first or current movement can take place.

30 544 How is this additional excitation of MImvt1 generated by the basal ganglia? Well, let s go through the loop cell by cell, using the schematic drawing below. The SMAmvt1 cortical cell will excite, via its corticostriate projection, a striatal neuron (caudate or putamen) via release of glutamate. This excitatory input turns on what is called a spiny striatal neuron (has lots of dendritic spines). The striatal cell, which uses the inhibitory transmitter GABA, sends its axon to, and inhibits, a cell in the GPi. The cell in the GPi, which also use GABA, projects via either the ansa lenticularis or lenticular fasciculus to a cell in the VA/VL (thalamus) that projects to, and excites, the MImvt1 cell. So, the SMAmvt1 signal excites a striatal neuron, which results in more inhibition flowing out of the striatum to the GPi. This inhibition of the GPi means LESS inhibition reaching VA/VL. This in turn will INCREASE THE FIRING OF VA/VL AND IN TURN THE FIRING OF MImvt1. You of course remember that MImvt1 is also being excited by direct (cortico-cortical) input from SMAmvt1. Remember, only the MImvt1 cells that are involved in the current movement have increased their firing rate. Moreover, it takes the direct cortico-cortical input from SMAmvt1 AND the SMAmvt1 loop through the basal ganglia to enable the MImvt1 cells to reach a high enough firing rate to generate the first or current movement in a sequence. Once you get those MImvt1 corticospinals firing enough action potentials, the LMNs do the labor for movement 1 (move muscles 1, 2, 3). The pathway through the basal ganglia just described is called the Direct Pathway through the basal ganglia (don t confuse it with the direct cortico-cortical projection from SMAmvt1 to MImvt1). It is called the Direct Pathway through the basal ganglia because it has fewer synaptic stations than the Indirect Pathway through the basal ganglia, which we will discuss next. Try these few practice questions to see how you are doing! If you find you re having any problems with these, go back and read the section again! We understand that this is difficult material!