Although Mr. J., a 48-year-old photographer, had just had a severe stroke that damaged much of his left parietal lobe, he was still a pleasant, cheerful, and likable man. His neurologist, Dr. R., introduced Mr. J. to us, and he sat down in a chair in front of the room.

“Mr. J., will you please show us how to wave hello?” asked Dr. R. The patient made a clumsy movement with his right hand and smiled apologetically. “Hold up your index finger, like this,” said Dr. R., pointing toward the ceiling. Mr. J. held up his hand, pursed his lips together, and, with a determined look on his face, clenched and unclenched his fist. Clearly, he was trying as hard as he could to point with his index finger, but he just could not move it without also moving his other fingers. “Can you hold your hand like this?” asked Dr. R., who held his hand in front of himself, palm down. Mr. J. watched him and, with obvious effort, copied the movement. “That’s good! Now turn your hand over.” Mr. J. grunted and began slapping his hand against his thigh. It looked to us as if he were trying to make the requested movement, but the wrong one was coming in its place. Dr. R. took hold of Mr. J.’s hand and, with great effort (Mr. J. was a strong man), managed to turn it over. “Good, now turn it over again.” Mr. J. began slapping his thigh with the back of his hand. Several times, Dr. R. helped him turn his hand over; but despite his efforts, Mr. J. was unable to do so by himself. He appeared to have very poor control of his movements.

Dr. R. addressed the rest of us. “You can see that Mr. J.’s apraxia is severe. But now watch this.” He turned to Mr. J. “Will you please take off your glasses?” Mr. J. reached up to his glasses, took hold of the earpieces, and smoothly removed them. “Fine. Now put them back on.” He did so. Dr. R. then asked, “Do you know what a hammer is?” “Sure,” answered Mr. J. “Okay, will you show us how you would use a hammer?” Mr. J. looked at his hand and then began slapping it against his thigh, as he had done before. “Okay, you can stop.” Mr. J. continued slapping his thigh, harder and harder. “Stop! That’s enough.” With great effort Mr. J. finally ceased making the movements. “Now let’s try this,” said Dr. R., who placed a block of wood on the table in front of Mr. J. and handed him a hammer and a nail. “Can you pound the nail into the wood?” Mr. J. held the nail upright with the fingers of his left hand, grasped the hammer with his right hand, and skillfully drove the nail into the wood.

After Mr. J. had left, Dr. R. said, “Mr. J.’s problem is not that he cannot make skilled movements, but that he cannot make these movements when we ask him to. He can manipulate his glasses and he can use a hammer, but he can’t make even the simplest voluntary movements out of context. Did you notice that he waved to you when I introduced him, even though he couldn’t do so when I asked him to show us how to wave ‘hello’?” We sheepishly admitted that we hadn’t been that observant. “The movement was an automatic one that he had learned to make long ago, and it was triggered by the fact that he was meeting other people. The left parietal lobe is involved in the control of movements—especially sequences of movements—that are not dictated by the context. Thus, he finds it almost impossible to follow verbal requests to make arbitrary movements.”

So far, I have described the nature of neural communication, the basic structure of the nervous system, and the physiology of perception. Now it is time to consider the ultimate function of the nervous system: control of behavior. The brain is the organ that moves the muscles. It does many other things, but all of them are secondary to making our bodies (or parts of them) move. This chapter describes the principles of muscular contraction, some reflex circuitry within the spinal cord, and the means by which the brain initiates behaviors. The rest of the book describes the physiology of particular categories of behaviors and the ways in which our behaviors can be modified by experience.

Skeletal Muscle

Skeletal muscles are the ones that move us (our skeletons) around and thus are responsible for our actions. Most of them are attached to bones at each end and move the bones when they contract. (Exceptions include eye muscles and some abdominal muscles, which are attached to bone at one end only.) Muscles are fastened to bones via tendons, strong bands of connective tissue. Several different classes of movement can be accomplished by the skeletal muscles, but I will refer principally to two of them: flexion and extension. Contraction of a flexor muscle produces flexion , the drawing in of a limb. Extension , which is the opposite movement, is produced by contraction of extensor muscles. These are the so-called antigravity muscles—the ones we use to stand up. When a four-legged animal lifts a paw, the movement is one of flexion. Putting it back down is one of extension. Sometimes, people say that they “flex” their muscles. This is an incorrect use of the term. Muscles contract; limbs flex. Bodybuilders show off their arm muscles by simultaneously contracting the flexor and extensor muscles of that limb.

skeletal muscle One of the striated muscles attached to bones.

flexion A movement of a limb that tends to bend its joints; the opposite of extension.

extension A movement of a limb that tends to straighten its joints; the opposite of flexion.

FIGURE 8.1 Anatomy of Skeletal Muscle

Anatomy

The detailed structure of a skeletal muscle is shown in Figure 8.1 . As you can see, it consists of two types of muscle fibers. The extrafusal muscle fibers are served by axons of the alpha motor neurons . Contraction of these fibers provides the muscle’s motive force. The intrafusal muscle fibers are specialized sensory organs that are served by two axons, one sensory and one motor. These organs are also called muscle spindles because of their shape. In fact, the Latin word fusus means “spindle”; hence, intrafusalmuscle fibers are found within the spindles, and extrafusal muscle fibers are found outside them.

extrafusal muscle fiber One of the muscle fibers that are responsible for the force exerted by contraction of a skeletal muscle.

alpha motor neuron A neuron whose axon forms synapses with extrafusal muscle fibers of a skeletal muscle; activation contracts the muscle fibers.

intrafusal muscle fiber A muscle fiber that functions as a stretch receptor, arranged parallel to the extrafusal muscle fibers, thus detecting changes in muscle length.

The central region (capsule) of the intrafusal muscle fiber contains sensory endings that are sensitive to stretch applied to the muscle fiber. Actually, there are two types of intrafusal muscle fibers, but for simplicity’s sake, only one kind is shown here. The efferent axon of the gamma motor neuron causes the intrafusal muscle fiber to contract; however, this contraction contributes an insubstantial amount of force. As we will see, the function of this contraction is to modify the sensitivity of the fiber’s afferent ending to stretch.

gamma motor neuron A neuron whose axons form synapses with intrafusal muscle fibers.

A single myelinated axon of an alpha motor neuron serves several extrafusal muscle fibers. In primates the number of muscle fibers served by a single axon varies considerably, depending on the precision with which the muscle can be controlled. In muscles that move the fingers or eyes, the ratio can be less than one to ten; in muscles that move the leg, it can be one to several hundred. An alpha motor neuron, its axon, and associated extrafusal muscle fibers constitute a motor unit .

motor unit A motor neuron and its associated muscle fibers.

A single muscle fiber consists of a bundle of myofibrils , each of which consists of overlapping strands of actin and myosin . Note the small protrusions on the myosin filaments; these structures (myosin cross bridges) are the motile elements that interact with the actin filaments and produce muscular contractions. (Look again at Figure 8.1 . ) The regions in which the actin and myosin filaments overlap produce dark stripes, or striations; hence, skeletal muscle is often referred to as striated muscle .

myofibril An element of muscle fibers that consists of overlapping strands of actin and myosin; responsible for muscular contractions.

actin One of the proteins (with myosin) that provide the physical basis for muscular contraction.

myosin One of the proteins (with actin) that provide the physical basis for muscular contraction.

striated muscle Skeletal muscle; muscle that contains striations.

The Physical Basis of Muscular Contraction

The synapse between the terminal button of an efferent neuron and the membrane of a muscle fiber is called a neuromuscular junction . The terminal buttons of the neurons synapse on motor endplates , located in grooves along the surface of the muscle fibers. When an axon fires, acetylcholine is liberated by the terminal buttons and produces a depolarization of the postsynaptic membrane—an endplate potential . The endplate potential is much larger than an excitatory postsynaptic potential in synapses between neurons; an endplate potential always causes the muscle fiber to fire, propagating the potential along its length. This action potential induces a contraction, or twitch, of the muscle fiber.

neuromuscular junction The synapse between the terminal buttons of an axon and a muscle fiber.

motor endplate The postsynaptic membrane of a neuromuscular junction.

endplate potential The postsynaptic potential that occurs in the motor endplate in response to release of acetylcholine by the terminal button.

The depolarization of a muscle fiber opens the gates of voltage-dependent calcium channels, permitting calcium ions to enter the cytoplasm. This event triggers the contraction. Calcium acts as a cofactor that permits the myofibrils to extract energy from the ATP that is present in the cytoplasm. The myosin cross bridges alternately attach to the actin strands, bend in one direction, detach themselves, bend back, reattach to the actin at a point farther down the strand, and so on. Thus, the cross bridges “row” along the actin filaments. Figure 8.2 illustrates this rowing sequence and shows how this sequence results in shortening the muscle fiber. (See Figure 8.2 . )

A single impulse of a motor neuron produces a single twitch of a muscle fiber. The physical effects of the twitch last considerably longer than will the action potential, because of the elasticity of the muscle and the time required to rid the cell of calcium. (Like sodium, calcium is actively extruded by a pump situated in the membrane.) Figure 8.3 shows how the physical effects of a series of action potentials can overlap, causing a sustained contraction by the muscle fiber. A single motor unit in a leg muscle of a cat can raise a 100-gram weight, which attests to the remarkable strength of the contractile mechanism. (See Figure 8.3 . )

As you know from your own experience, muscular contraction is not an all-or-nothing phenomenon, as are the twitches of the constituent muscle fibers. Obviously, the strength of a muscular contraction is determined by the average rate of firing of the various motor units. If, at a given moment, many units are firing, the contraction will be forceful. If few are firing, the contraction will be weak.

Sensory Feedback from Muscles

As we saw, the intrafusal muscle fibers contain sensory endings that are sensitive to stretch. The intrafusal muscle fibers are arranged in parallel with the extrafusal muscle fibers. Therefore, they are stretched when the muscle lengthens and are relaxed when it shortens. Thus, even though these afferent neurons are stretch receptors, they serve as muscle length detectors. This distinction is important. Stretch receptors are also located within the tendons, in the Golgi tendon organ . These receptors detect the total amount of stretch exerted by the muscle, through its tendons, on the bones to which the muscle is attached. The stretch receptors of the Golgi tendon organ encode the degree of stretch by the rate of firing. They respond not to a muscle’s length but to how hard it is pulling. In contrast, the receptors on intrafusal muscle fibers detect muscle length, not tension.

Golgi tendon organ The receptor organ at the junction of the tendon and muscle that is sensitive to stretch.

FIGURE 8.2 Mechanism of Muscular Contraction

(a) Cross section through a myosin filament and the surrounding actin filaments. (b) The myosin cross bridges performing “rowing” movements, which cause the actin and myosin filaments to move relative to each other. For the sake of clarity, only two actin filaments are shown.

FIGURE 8.3 Action Potentials and Contractions of a Muscle Fiber

A rapid succession of action potentials can cause a muscle fiber to produce a sustained contraction. Each dot represents an individual action potential.

(Adapted from Devanandan, M. S., Eccles, R. M., and Westerman, R. A. Journal of Physiology [London], 1965, 178, 359–367.)

Figure 8.4 shows the response of afferent axons of the muscle spindles and Golgi tendon organ to various types of movements. Figure 8.4(a) shows the effects of passive lengthening of muscles, the kind of movement that would be seen if your forearm, held in a completely relaxed fashion, were slowly lowered by someone who was supporting it. The rate of firing of one type of muscle spindle afferent neuron (MS1) increases, while the activity of the afferent of the Golgi tendon organ remains unchanged. (See Figure 8.4a . ) Figure 8.4(b) shows the results when the arm is dropped quickly; note that this time the second type of muscle spindle afferent neuron (MS2) fires a rapid burst of impulses. This fiber, then, signals rapid changes in muscle length. (See Figure 8.4b . ) Figure 8.4(c) shows what would happen if a weight were suddenly dropped into your hand while your forearm was held parallel to the ground. Neurons MS1 and MS2 (especially MS2, which responds to rapid changes in muscle length) briefly fire, because your arm lowers briefly and then comes back to the original position. The Golgi tendon organ, monitoring the strength of contraction, fires in proportion to the stress on the muscle, so it increases its rate of firing as soon as the weight is added. (See Figure 8.4c . )

FIGURE 8.4 Responses of Muscle and Tendon Receptors

The figure shows effects of arm movements on the firing of muscle and tendon afferent axons: (a) slow, passive extension of the arm; (b) rapid extension of the arm; (c) addition of a weight to an arm held in a horizontal position. MS1 and MS2 are two types of muscle spindles; GTO is an afferent fiber from the Golgi tendon organ.

SECTION SUMMARY: Skeletal Muscle

Skeletal muscles contain extrafusal muscle fibers, which provide the force of contraction. The alpha motor neurons form synapses with the extrafusal muscle fibers and control their contraction. Skeletal muscles also contain intrafusal muscle fibers, which detect changes in muscle length. The length of the intrafusal muscle fiber, and hence its sensitivity to increases in muscle length, is controlled by the gamma motor neuron. Besides the intrafusal muscle fibers, the muscles contain stretch receptors in the Golgi tendon organs, located at the ends of the muscles.

The force of muscular contraction is provided by long protein molecules called actin and myosin, arranged in overlapping parallel arrays. When an action potential, initiated by the synapse at the motor endplate, causes calcium ions to enter the muscle fiber, the myofibrils extract energy from ATP and cause a twitch of the muscle fiber, producing a ratchetlike “rowing” movement of the myosin cross bridges.

Reflexive Control of Movement

Although behaviors are controlled by the brain, the spinal cord possesses a certain degree of autonomy. Particular kinds of somatosensory stimuli can elicit rapid responses through neural connections located within the spinal cord. These reflexes constitute the simplest level of motor integration.

The Monosynaptic Stretch Reflex

The activity of the simplest functional neural pathway in the body is easy to demonstrate. Sit on a surface high enough to allow your legs to dangle freely and have someone lightly tap your patellar tendon, just below the kneecap. This stimulus briefly stretches your quadriceps muscle, on the top of your thigh. The stretch causes the muscle to contract, which makes your leg kick forward. (I am sure few of you will bother with this demonstration, because you are already familiar with it; physical examinations often include a test of this reflex.) The time interval between the tendon tap and the start of the leg extension is about 50 milliseconds. That interval is too short for the involvement of the brain; it would take considerably longer for sensory information to be relayed to the brain and for motor information to be relayed back. For example, suppose a person is asked to move his or her leg as quickly as possible after being touched on the knee. This response would not be reflexive but would involve sensory and motor mechanisms of the brain. In this case the interval between the stimulus and the start of the response would be several times greater than the time required for the patellar reflex.

Obviously, the patellar reflex as such has no utility; no selective advantage is bestowed on animals that kick a limb when a tendon is tapped. However, if a more natural stimulus is applied, the utility of this mechanism becomes apparent. Figure 8.5 shows the effects of placing a weight in a person’s hand. This time I have included a piece of the spinal cord, with its roots, to show the neural circuit that composes the monosynaptic stretch reflex . First, follow the circuit: Starting at the muscle spindle, afferent impulses are conducted to terminal buttons in the gray matter of the spinal cord. These terminal buttons synapse on an alpha motor neuron that innervates the extrafusal muscle fibers of the same muscle. Only one synapse is encountered along the route from receptor to effector—hence the term monosynaptic. (See Figure 8.5a . )

monosynaptic stretch reflex A reflex in which a muscle contracts in response to its being quickly stretched; involves a sensory neuron and a motor neuron, with one synapse between them.

Now consider a useful function this reflex performs. If the weight the person is holding is increased, the forearm begins to move downward. This movement lengthens the muscle and increases the firing rate of the muscle spindle afferent neurons, whose terminal buttons then stimulate the alpha motor neurons, increasing their rate of firing. Consequently, the strength of the muscular contraction increases, and the arm pulls the weight up. (See Figure 8.5b . )

Another important role played by the monosynaptic stretch reflex is control of posture. To stand, we must keep our center of gravity above our feet, or we will fall. As we stand, we tend to oscillate forward and back and from side to side. Our vestibular sacs and our visual system play important roles in the maintenance of posture. However, these systems are aided by the activity of the monosynaptic stretch reflex. For example, consider what happens when a person begins to lean forward. The large calf muscle (gastrocnemius) is stretched, and this stretching elicits compensatory muscular contraction that pushes the toes downward, thus restoring upright posture. (See Figure 8.6 . )

The Gamma Motor System

Muscle spindles are very sensitive to changes in muscle length; they will increase their rate of firing when the muscle is lengthened by a very small amount. The interesting thing is that this detection mechanism is adjustable. Remember that the ends of the intrafusal muscle fibers can be contracted by activity of the associated efferent axons of the gamma motor neurons; their rate of firing determines the degree of contraction. When the muscle spindles are relaxed, they are relatively insensitive to stretch. However, when the gamma motor neurons are active, they become shorter and hence become much more sensitive to changes in muscle length. This property of adjustable sensitivity simplifies the role of the brain in controlling movement. The more control that can occur in the spinal cord, the fewer messages must be sent to and from the brain.

We have already seen that the afferent axons of the muscle spindle help to maintain limb position even when the load carried by the limb is altered. Efferent control of the muscle spindles permits these muscle length detectors to assist in changes in limb position as well. Consider a single muscle spindle. When its efferent axon is completely silent, the spindle is completely relaxed and extended. As the firing rate of the efferent axon increases, the spindle gets shorter and shorter. If, simultaneously, the rest of the entire muscle also gets shorter, there will be no stretch on the central region that contains the sensory endings, and the afferent axon will not respond. However, if the muscle spindle contracts faster than does the muscle as a whole, there will be a considerable amount of afferent activity.

FIGURE 8.5 The Monosynaptic Stretch Reflex

(a) Neural circuit. (b) A useful function.

FIGURE 8.6 The Role of the Monosynaptic Stretch Reflex in Postural Control

The motor system makes use of this phenomenon in the following way: When commands from the brain are issued to move a limb, both the alpha motor neurons and the gamma motor neurons are activated. The alpha motor neurons start the muscle contracting. If there is little resistance, both the extrafusal and intrafusal muscle fibers will contract at approximately the same rate, and little activity will be seen from the afferent axons of the muscle spindle. However, if the limb meets with resistance, the intrafusal muscle fibers will shorten more than the extrafusal muscle fibers, and hence sensory axons will begin to fire and cause the monosynaptic stretch reflex to strengthen the contraction. Thus, the brain makes use of the gamma motor system in moving the limbs. By establishing a rate of firing in the gamma motor system, the brain controls the length of the muscle spindles and, indirectly, the length of the entire muscle.

Polysynaptic Reflexes

The monosynaptic stretch reflex is the only spinal reflex we know of that involves only one synapse. All others are polysynaptic. Examples include relatively simple ones, such as limb withdrawal in response to noxious stimulation, and relatively complex ones, such as the ejaculation of semen. Spinal reflexes do not exist in isolation; they are normally controlled by the brain. For example, Chapter 2 described how inhibition from the brain can prevent a person from dropping a hot casserole dish, even though the painful stimuli received by the fingers cause reflexive extension of the fingers. This section will describe some general principles by which polysynaptic spinal reflexes operate.

Before I begin the discussion, I should mention that the simple circuit diagrams used here (including the one you just looked at in Figure 8.6 ) are much too simple. Reflex circuits are typically shown as a single chain of neurons, but in reality most reflexes involve thousands of neurons. Each axon usually synapses on many neurons, and each neuron receives synapses from many different axons.

FIGURE 8.7 Polysynaptic Inhibitory Reflex

Input from the Golgi tendon organ can cause inhibitory postsynaptic potentials to occur on the alpha motor neuron.

As we saw previously, the afferent axons from the Golgi tendon organ serve as detectors of muscle stretch. There are two populations of afferent axons from the Golgi tendon organ, with different sensitivities to stretch. The more sensitive afferent axons tell the brain how hard the muscle is pulling. The less sensitive ones have an additional function. Their terminal buttons synapse on spinal cord interneurons—neurons that reside entirely within the gray matter of the spinal cord and serve to interconnect other spinal neurons. These interneurons synapse on the alpha motor neurons serving the same muscle. The terminal buttons liberate glycine and hence produce inhibitory postsynaptic potentials on the motor neurons. (See Figure 8.7 . ) The function of this reflex pathway is to decrease the strength of muscular contraction when there is danger of damage to the tendons or bones to which the muscles are attached.

The discovery of the inhibitory Golgi tendon organ reflex provided the first real evidence of neural inhibition, long before the synaptic mechanisms were understood. A decerebrate cat, whose brain stem has been cut through, exhibits a phenomenon known as decerebrate rigidity . The animal’s back is arched, and its legs are extended stiffly from its body. This rigidity results from excitation originating in the caudal reticular formation, a region of the brain stem, which greatly facilitates all stretch reflexes, especially of extensor muscles, by increasing the activity of the gamma motor system. Rostral to the brain stem transection is an inhibitory region of the reticular formation that normally counterbalances the excitatory one. The transection removes the inhibitory influence, leaving only the excitatory one. If you attempt to flex the outstretched leg of a decerebrate cat, you will meet with increasing resistance, which will suddenly melt away, allowing the limb to flex. It almost feels as though you were closing the blade of a pocketknife—hence the term clasp-knife reflex . The sudden release is, of course, mediated by activation of the Golgi tendon organ reflex.

decerebrate Describes an animal whose brain stem has been transected.

decerebrate rigidity Simultaneous contraction of agonistic and antagonistic muscles; caused by decerebration or damage to the reticular formation.

clasp-knife reflex A reflex that occurs when force is applied to flex or extend the limb of an animal showing decerebrate rigidity; resistance is replaced by sudden relaxation.

SECTION SUMMARY: Reflexive Control of Movement

Reflexes are simple circuits of sensory neurons, interneurons (usually), and efferent neurons that control simple responses to particular stimuli. In the monosynaptic stretch reflex the terminal buttons of axons that receive sensory information from the intrafusal muscle fibers synapse with alpha motor neurons that innervate the same muscle. Thus, a sudden lengthening of the muscle causes the muscle to contract. By setting the length of the intrafusal muscle fibers, and hence their sensitivity to increases in muscle length, the motor system of the brain can control limb position. Changes in a weight being held that cause the limb to move will be quickly compensated for by means of the monosynaptic stretch reflex.

Polysynaptic reflexes contain at least one inter-neuron between the sensory neuron and the motor neuron. For example, when a strong muscular contraction threatens to damage muscles or limbs, the increased rate of firing of the afferent axons of Golgi tendon organs stimulates inhibitory interneurons, which inhibit the alpha motor neurons of those muscles.

▪ THOUGHT QUESTION

Weight lifters can lift heavier weights if their Golgi tendon organs are deactivated with injections of a local anesthetic. Considering the normal function of these organs, why would these injections be unwise?

Control of Movement by the Brain

Movements can be initiated by several means. For example, rapid stretch of a muscle triggers the monosynaptic stretch reflex, a stumble triggers righting reflexes, and the rapid approach of an object toward the face causes a startle response, a complex reflex consisting of movements of several muscle groups. Other stimuli initiate sequences of movements that we have previously learned. For example, the presence of food causes eating, and the sight of a loved one evokes a hug and a kiss. Because there is no single cause of behavior, we cannot find a single starting point in our search for the neural mechanisms that control movement.

The brain and spinal cord include several different motor systems, each of which can simultaneously control particular kinds of movements. For example, a person can walk and talk with a friend simultaneously. While doing so, the person can gesture with the hands to emphasize a point, scratch an itch, brush away a fly, wipe sweat off his or her forehead, and so on. Walking, postural adjustments, talking, movement of the arms, and movements of the fingers all involve different specialized motor systems.

FIGURE 8.8 Motor Cortex and the Motor Homunculus

Stimulation of various regions of the primary motor cortex causes movement in muscles of various parts of the body.

Organization of the Motor Cortex

The primary motor cortex lies on the precentral gyrus, just rostral to the central sulcus. Stimulation studies (including those in awake humans) have shown that the activation of neurons located in particular parts of the primary motor cortex causes movements of particular parts of the body. In other words, the primary motor cortex shows somatotopic organization (from soma, “body,” and topos, “place”). Figure 8.8 shows a motor homunculus based on the observations of Penfield and Rasmussen ( 1950 ). Note that a disproportionate amount of cortical area is devoted to movements of the fingers and the muscles used for speech. (See Figure 8.8 . )

somatotopic organization A topographically organized mapping of parts of the body that are represented in a particular region of the brain.

Figure 8.9 shows the results of a combined fMRI and DTI study by Wahl et al. ( 2007 ), which shows an image of regions of the primary motor cortex and the axons of the corpus callosum that unite regions of the left and right primary motor cortex. The cortical regions that control movements in the lips, hand, and foot are shown in light red, light green, and light yellow, respectively. The axons of the corpus callosum that unite these regions are shown in darker versions of the same colors. (See Figure 8.9 . )

FIGURE 8.9 Regions of the Primary Motor Cortex and Associated Axons of the Corpus Callosum

The figures show images of regions of the primary motor cortex of the right and left hemispheres that control movements of the lips (light red), hand (light green) and foot (light yellow). The axons of the corpus callosum that unite these regions are shown in darker versions of the same colors. (a) Horizontal view. (b) Cross-sectional view.

(From Wahl, M., Lauterbach-Soon, B., Hattinger, E., et al. Journal of Neuroscience, 2007, 27, 12132–12138. Reprinted with permission.)

It is important to recognize that the primary motor cortex is organized in terms of particular movementsof particular parts of the body. Each movement may be accomplished by the contraction of several muscles. For example, when the arm is extended in a particular direction, many muscles in the shoulder, upper arm, and forearm must contract. This fact means that complex neural circuitry is located between individual neurons in the primary motor cortex and the motor neurons in the spinal cord that cause motor units to contract. As we will see, the commands for movement initiated in the motor cortex are assisted and modified—most notably, by the basal ganglia and the cerebellum.

A study by Graziano and Aflalo ( 2007 ) found that although brief stimulation of particular regions of the primary motor cortex of monkeys caused brief movements of various parts of the body, prolonged stimulation produced much more complex movements. For example, stimulation of one region caused the hand to close and then approach the mouth and the mouth then to open. Stimulation of another region caused the face to squint, the head to turn quickly to one side, and the arms to fling up, as if to protect the face from something that was going to hit it. Stimulation of different zones of the motor cortex caused different categories of actions. The map of these categories was consistent from animal to animal. (See Figure 8.10 . )

FIGURE 8.10 Stimulation of the Motor Cortex

Categories of movements elicited by prolonged stimulation of specific regions of the motor cortex of monkeys.

(Adapted from Graziano, M. S. A., and Aflalo, T. N. Neuron, 2007, 56, 239–251.)

The principal cortical input to the primary motor cortex is the frontal association cortex, located rostral to it. Two regions immediately adjacent to the primary motor cortex—the supplementary motor area and the premotor cortex—are especially important in the control of movement. Both regions receive sensory information from the parietal and temporal lobes, and both send efferent axons to the primary motor cortex. The supplementary motor area (SMA) is located on the medial surface of the brain, just rostral to the primary motor cortex. The premotor cortex is located primarily on the lateral surface, also just rostral to the primary motor cortex. The roles that these regions play in the control of movement is discussed later in this chapter. (Refer back to Figure 8.8 . )

supplementary motor area (SMA) A region of motor association cortex of the dorsal and dorsomedial frontal lobe, rostral to the primary motor cortex.

premotor cortex A region of motor association cortex of the lateral frontal lobe, rostral to the primary motor cortex.

Cortical Control of Movement: The Descending Pathways

Neurons in the primary motor cortex control movements by two groups of descending tracts, the lateral group and the ventromedial group , named for their locations in the white matter of the spinal cord. The lateral group consists of the corticospinal tract, the corticobulbar tract, and the rubrospinal tract. This system is primarily involved in control of independent limb movements, particularly movements of the hands and fingers. Independent limb movements mean that the right and left limbs make different movements or one limb moves while the other remains still. These movements contrast with coordinated limb movements, such as those involved in locomotion. The ventromedial group consists of the vestibulospinal tract, the tectospinal tract, the reticulospinal tract, and the ventral corticospinal tract.These tracts control more automatic movements: gross movements of the muscles of the trunk and coordinated trunk and limb movements involved in posture and locomotion.

lateral group The corticospinal tract, the corticobulbar tract, and the rubrospinal tract.

ventromedial group The vestibulospinal tract, the tectospinal tract, the reticulospinal tract, and the ventral corticospinal tract.

FIGURE 8.11 Lateral Group of Descending Motor Tracts

The figure shows the lateral corticospinal tract (light blue lines), corticobulbar tract (green lines), and rubrospinal tract (red lines). The ventral corticospinal tract (dark blue lines) is part of the ventromedial group.

Let’s first consider the lateral group of descending tracts. The corticospinal tract consists of axons of cortical neurons that terminate in the gray matter of the spinal cord. The largest concentration of cell bodies responsible for these axons is located in the primary motor cortex, but neurons in the parietal and temporal lobes also send axons through the corticospinal pathway. The axons leave the cortex and travel through subcortical white matter to the ventral midbrain, where they enter the cerebral peduncles. They leave the peduncles in the medulla and form the pyramidal tracts , so called because of their shape. At the level of the caudal medulla, most of the fibers decussate (cross over) and descend through the contralateral spinal cord, forming the lateral corticospinal tract . The rest of the fibers descend through the ipsilateral spinal cord, forming the ventral corticospinal tract . Because of its location and function, the ventral corticospinal tract is actually part of the ventromedial group. (See the light and dark blue lines in Figure 8.11 . )

corticospinal tract The system of axons that originates in the motor cortex and terminates in the ventral gray matter of the spinal cord.

pyramidal tract The portion of the corticospinal tract on the ventral border of the medulla.

lateral corticospinal tract The system of axons that originates in the motor cortex and terminates in the contralateral ventral gray matter of the spinal cord; controls movements of the distal limbs.

ventral corticospinal tract The system of axons that originates in the motor cortex and terminates in the ipsilateral ventral gray matter of the spinal cord; controls movements of the upper legs and trunk.

Most of the axons in the lateral corticospinal tract originate in the regions of the primary motor cortex and supplementary motor area that control the distal parts of the limbs: the arms, hands, and fingers and the lower legs, feet, and toes. They form synapses, directly or via interneurons, with motor neurons in the gray matter of the spinal cord—in the lateral part of the ventral horn. These motor neurons control muscles of the distal limbs, including those that move the arms, hands, and fingers. (See the light blue lines in Figure 8.11 . )

The axons in the ventral corticospinal tract originate in the upper leg and trunk regions of the primary motor cortex. They descend to the appropriate region of the spinal cord and divide, sending terminal buttons into both sides of the gray matter. They control motor neurons that move the muscles of the upper legs and trunk. (See the dark blue lines in Figure 8.11 . )

The corticospinal pathway controls hand and finger movements and is indispensable for moving the fingers independently when reaching and manipulating. Postural adjustments of the trunk and use of the limbs for reaching and locomotion are controlled by other systems.

The second of the lateral group of descending pathways, the corticobulbar tract , projects to the medulla (sometimes called the bulb). This pathway is similar to the corticospinal pathway, except that it terminates in the motor nuclei of the fifth, seventh, ninth, tenth, eleventh, and twelfth cranial nerves (the trigeminal, facial, glossopharyngeal, vagus, spinal accessory, and hypoglossal nerves). These nerves control movements of the face, neck, and tongue and parts of the extraocular eye muscles. (See the green lines in Figure 8.11 . )

corticobulbar tract A bundle of axons from the motor cortex to the fifth, seventh, ninth, tenth, eleventh, and twelfth cranial nerves; controls movements of the face, neck, tongue, and parts of the extraocular eye muscles.

The third member of the lateral group is the rubrospinal tract . This tract originates in the red nucleus (nucleus ruber) of the midbrain. The red nucleus receives its most important inputs from the motor cortex via the corticorubral tract and (as we shall see later) from the cerebellum. Axons of the rubrospinal tracts terminate on motor neurons in the spinal cord that control independent movements of the forearms and hands—that is, movements that are independent of trunk movements. (They do not control the muscles that move the fingers.) (See the red lines in Figure 8.11 . )

rubrospinal tract The system of axons that travels from the red nucleus to the spinal cord; controls independent limb movements.

corticorubral tract The system of axons that travels from the motor cortex to the red nucleus.

Now let’s consider the second set of pathways originating in the brain stem: the ventromedial group. This group includes the vestibulospinal tracts , the tectospinal tracts , and the reticulospinal tracts , as well as the ventral corticospinal tract (already described). These tracts control motor neurons in the ventromedial part of the spinal cord gray matter. Neurons of all these tracts receive input from the portions of the primary motor cortex that control movements of the trunk and proximal muscles (that is, the muscles located on the parts of the limbs close to the body). In addition, the reticular formation receives a considerable amount of input from the premotor cortex and from several subcortical regions, including the amygdala, hypothalamus, and basal ganglia. The cell bodies of neurons of the vestibulospinal tracts are located in the vestibular nuclei. As you might expect, this system plays a role in the control of posture. The cell bodies of neurons in the tectospinal tracts are located in the superior colliculus and are involved in coordinating head and trunk movements with eye movements. The cell bodies of neurons of the reticulospinal tracts are located in many nuclei in the brain stem and midbrain reticular formation. These neurons control several automatic functions, such as muscle tonus, respiration, coughing, and sneezing; but they are also involved in behaviors that are under direct neocortical control, such as walking. (See Figure 8.12 . )

vestibulospinal tract A bundle of axons that travels from the vestibular nuclei to the gray matter of the spinal cord; controls postural movements in response to information from the vestibular system.

tectospinal tract A bundle of axons that travels from the tectum to the spinal cord; coordinates head and trunk movements with eye movements.

reticulospinal tract A bundle of axons that travels from the reticular formation to the gray matter of the spinal cord; controls the muscles responsible for postural movements.

Table 8.1 summarizes the names of these pathways, their locations, and the muscle groups they control. (See Table 8.1 . )

Planning and Initiating Movements: Role of the Motor Association Cortex

The supplementary motor area and the premotor cortex are involved in the planning of movements, and they execute these plans through their connections with the primary motor cortex. Functional-imaging studies show that when people execute sequences of movements—or even imagine them—these regions become activated (Roth et al., 1996 ). More recent evidence indicates that the motor association cortex is also involved in imitating the actions of other people (an ability that makes it possible to learn new behaviors from them) and even in understanding the functions of other people’s behavior.

The supplementary motor area and the premotor cortex receive information from association areas of the parietal and temporal cortex. As we saw in Chapter 6 , the visual association cortex is organized in two streams: dorsal and ventral. The ventral stream, which terminates in the inferior temporal cortex, is involved in perceiving and recognizing particular objects—the “what” of visual perception. The dorsal stream, which terminates in the posterior parietal lobe, is involved in perception of location—the “where” of visual perception. In addition, the parietal lobes are involved in organizing visually guided movements that interact with objects in the environment—the “how” of visual perception. Besides receiving information about space from the visual system, the parietal lobe receives information about spatial location from the somatosensory, vestibular, and auditory systems and integrates this information with visual information. Thus, the regions of the frontal cortex that are involved in planning movements receive the information they need about what is happening and where it is happening from the temporal and parietal lobes. Because the parietal lobes contain spatial information, the pathway from them to the frontal lobes is especially important in controlling both locomotion and arm and hand movements. After all, meaningful locomotion requires us to know where we are, and meaningful movements of our arms and hands require us to know where objects are located in space. (See Figure 8.13 . )

FIGURE 8.12 Ventromedial Group of Descending Motor Tracts

The figure shows the tectospinal tract (blue lines), lateral reticulospinal tract (purple lines), medial reticulospinal tract (orange lines), and vestibulospinal tract (green lines).

Let’s look at the functions of the supplementary motor area and the premotor cortex in more detail. In general, the supplementary motor cortex is involved in learning and performing behaviors that consist of sequences of movements. The premotor cortex is involved in learning and executing responses that are signaled by the presence of arbitrary stimuli. As a component of the mirror neurons system, it is also imitating responses of other people and in understanding and predicting these actions.

THE SUPPLEMENTARY MOTOR AREA

The supplementary motor area plays a critical role in behavioral sequences. Damage to this region disrupts the ability to execute well-learned sequences of responses in which the performance of one response serves as the signal that the next response must be made. Chen et al. ( 1995 ) found that lesions of the supplementary motor area severely impaired monkeys’ ability to perform a simple sequence of two responses: pushing a lever in and then turning it to the left, receiving a peanut after each response. (See Figure 8.14 . )

A single-unit recording study came to similar conclusions. Mushiake, Inase, and Tanji ( 1991 ) trained monkeys to perform a memorized series of responses, pressing each of three buttons in a specific sequence. While the monkeys were performing this task, more than half of the neurons in the supplementary motor area became activated. However, when the sequence was cued by visual stimuli—the monkeys simply had to press the button that was illuminated—these neurons showed little activity.

Shima and Tanji ( 2000 ) taught monkeys six sequences of three motor responses. For example, one of the sequences was push, then pull, then turn. They recorded from neurons in the supplementary motor area and found neurons whose activity appeared to encode elements of these sequences. For example, some neurons responded just before a particular sequence of three movements occurred; some neurons responded between two particular responses; and some neurons responded as the monkey was preparing the make the last response of the sequence. Presumably, these neurons were members of circuits that encoded the information necessary to perform the six sequences. Figure 8.15 shows the response of a neuron that responded during a pulling movement, but only if it was to be followed by a pushing movement. (See Figure 8.15 . )

TABLE 8.1 Major Motor Pathways

	Origin	Termination	Muscle Group	Function
Lateral Group
Lateral corticospinal tract	Finger, hand, and arm region of motor cortex	Spinal cord	Fingers, hands, and arms	Grasping and manipulating objects
Rubrospinal tract	Red nucleus	Spinal cord	Hands (not fingers), lower arms, feet, and lower legs	Movement of forearms and hands independent from that of the trunk
Corticobulbar tract	Face region of motor cortex	Cranial nerve nuclei: 5, 7, 9, 10, 11, and 12	Face and tongue	Face and tongue movements
Ventromedial Group
Vestibulospinal tract	Vestibular nuclei	Spinal cord	Trunk and legs	Posture
Tectospinal tract	Superior colliculi	Spinal cord	Neck and trunk	Coordination of eye movements with those of trunk and head
Lateral reticulospinal tract	Medullary reticular formation	Spinal cord	Flexor muscles of legs	Walking
Medial reticulospinal tract	Pontine reticular formation	Spinal cord	Extensor muscles of legs	Walking
Ventral corticospinal tract	Trunk and upper leg region of motor cortex	Spinal cord	Hands (not fingers), lower arms, feet, and lower legs	Locomotion and posture

FIGURE 8.13 Cortical Control of Movement

The posterior association cortex is involved with perceptions and memories, and the frontal association cortex is involved with plans for movement.

Shima and Tanji ( 1998 ) temporarily inactivated the supplementary motor area in monkeys with injections of muscimol, a drug that stimulates GABA receptors and thus inhibits neural activity. They found that after inactivation of this region, monkeys could still reach for objects or make particular movements in response to visual cues but could no longer make a sequence of three movements they had previously learned.

Studies with human subjects have obtained results similar to those obtained with monkeys. For example, a functional-imaging study by Hikosaka et al. ( 1996 ) observed increased activity in the posterior SMA during performance of a learned sequence of button presses. Gerloff et al. ( 1997 ) taught people to make a sequence of sixteen finger presses on an electronic piano. When the experimenters disrupted the activity of the SMA with transcranial magnetic stimulation, the performance of the sequence was disrupted. However, the disruption was not immediate: The subjects continued the sequence for approximately one second and then stopped, saying that they “did not know anymore which series of keys to press next.” Apparently, the SMA is involved in planning the elements yet to come in sequences of movements. The actual execution of the movements appears to be controlled elsewhere—presumably by the primary motor cortex.

FIGURE 8.14 Role of the SMA in Execution of Behavioral Sequences

The monkey was required to (1) push the handle in and then (2) turn it to the left, receiving a piece of food in the door above the lever after each component of the sequence.

(Adapted from Chen, Y.-C., Thaler, D., Nixon, P. D., et al. Experimental Brain Research, 1995, 102, 461–473.)

Once we have learned a sequence of movements using one hand, we can easily perform the sequence with the other hand. Presumably, the learning has taken place in the hemisphere that controls the hand that first performed the sequence. Perez et al. ( 2008 ) trained people to perform a twelve-item sequence of finger movements using four fingers of the right hand. While they were learning the task, the experimenters supplied transcranial magnetic stimulation (TMS) to the subjects’ left SMA with a sequence of pulses that temporarily disrupted the activity of this region. If the disrupting stimulation occurred just before each response was to be made, the subjects learned the task with their right hand but performed poorly when they were later tested with their left hand. If the stimulation occurred during each finger movement, transfer to the left hand was normal. Perez and her colleagues noted that the left and right SMA have strong interconnections and suggest that during the learning of the sequence, information about the previous response was transmitted from the left SMA to the right SMA. The disrupting TMS interfered with this transfer.

FIGURE 8.15 Firing Patterns of a Supplementary Motor Area Neuron

The figure shows the firing patterns of a single neuron in the supplementary motor area of a monkey. The animal performed three sequences of movements. The neuron responded only during a pulling response that was to be followed by a pushing response. Black hash marks indicate action potentials during each trial, and blue histograms indicate the total number of action potentials summed across all trials.

(From Shima, K., and Tanji, J. Journal of Neurophysiology, 2000, 84, 2148–2160. Reprinted with permission of the American Physiological Society.)

A region just anterior to the supplementary motor area, the pre-SMA, appears to be involved in control of spontaneous movements—or at least in the perception of control. It has long been known that although electrical stimulation of the motor cortex causes movements, it does not produce the desire to move. The movement is perceived as automatic and involuntary. In contrast, electrical stimulation of the medial surface of the frontal lobes (including the SMA and pre-SMA) often provokes the urge to make a movement or at least the anticipation that a movement is about to occur (Fried et al., 1991 ).

A functional-imaging study by Lau et al. ( 2004 ) found that the pre-SMA appears to play a role in voluntary behavior. They found that this region became active just before people performed spontaneous movements. The experimenters asked the subjects to make a finger movement from time to time, whenever they felt like doing so. The subjects watched a red light that moved around a clock face at about 2.5 sec per revolution. They were asked to pay attention to the instant when they decided to make the movement and report the position of the red dot at that time. The decision appeared to occur approximately 0.2 sec before the movement began. However, fMRI showed that the activity of the pre-SMA actually began to increase approximately 2–3 sec earlier than that, which suggests that the neural activity responsible for the decision to move begins before a person is even aware of making that decision. The results suggest that although we feel that we consciously decide when to make a response, the decision is actually made by brain processes of which we are unaware. We do not actually become aware of the decision until later.

Evidence suggests that the decision to move is not made by neurons in the SMA. Sirigu et al. ( 2004 ) used a task similar to the one in the study by Lau et al. to investigate decision making in people with lesions of the posterior parietal cortex. They found that people with these lesions could accurately report when they started the movement, but they were not aware of an intention to move prior to making the movement. The investigators suggest that neural activity in the posterior parietal cortex “generates a predictive internal model of the upcoming movement.”

What neural circuits are actually responsible for making a decision to move? Sirigu and her colleagues ( 2004 ) note that lesions of the prefrontal cortex (even more anterior than the pre-SMA) disrupt people’s plans for voluntary action. People with prefrontal lesions will react to events but show deficits in initiating behavior, so perhaps the prefrontal cortex is an important source of these decisions. The posterior parietal cortex may be involved in monitoring one’s own plans and intentions rather than directly forming these intentions.

A functional imaging study by Soon et al. ( 2008 ) found evidence that a region of the prefrontal cortex—the frontopolar cortex, located at the rostral tip of the cerebral hemispheres—may play a critical role in deciding to make a motor response. The investigators had subjects perform a task similar to the one used by Lau et al. ( 2004 ). The subjects were told to watch a screen that displayed a stream of letters and to press one of two buttons whenever they felt like it. The choice of button and the timing of the response was up to them. After each response, the subjects reported the letter they had seen on the screen at the time they decided to press one of the buttons, which indicated the time between the awareness of this decision and their movement—which averaged about one second. Examination of the pattern of brain activation on each trial enabled the investigators to predict the decision to press the right or left button. Approximately 10 sec before the response, the decision about which button should be pressed could accurately be predicted by particular patterns of activity in the frontopolar cortex. The decision could be predicted shortly thereafter by the pattern of activity in the posterior parietal cortex, and then by the activity in the SMA. Finally, the primary motor cortex became activated, causing the finger to move. These results suggest that the prefrontal cortex plays a critical role in decision making of the kind the investigators studied. The posterior parietal cortex appears to be involved in storing the information about the decision and transmitting it to the SMA, where the process of executing the response begins.

THE PREMOTOR CORTEX

The premotor cortex is involved in learning and executing complex movements that are guided by sensory information. The results of several studies suggest that the premotor cortex is involved in using arbitrary stimuli to indicate what movement should be made. For example, reaching for an object that we see in a particular location involves nonarbitrary spatial information; that is, the visual information provided by the location of the object specifies just where we should target our reaching movement. But we also have the ability to learn to make movements based on arbitrary information—information that is not directly related to the movement that it signals. For example, a person can point to a particular object when someone says its name, or a dancer can make a particular movement when asked to do so by a choreographer. Different languages use different sounds to indicate the names of objects, and different choreographers could invent different names for movements used in their dances. Or a person could be told to “wave your left hand when you hear the buzz and touch your nose when you hear the bell.” The associations between these stimuli and the movements they designate are arbitrary and must be learned.

Kurata and Hoffman ( 1994 ) trained monkeys to move their hand toward the right or left in response to either a spatial or a nonspatial signal. The spatial signal required the animals to move in the direction indicated by signal lights located to the right and left of its hand. The nonspatial signal consisted of a pair of lights, one red and one green, located in the middle of the display. The red light signaled a movement to the left, and the green light signaled a movement to the right. The investigators temporarily inactivated the premotor cortex with injections of muscimol. When this region was inactivated, the monkeys could still move their hand toward a signal light located to the left or right (a nonarbitrary signal), but they could no longer make the appropriate movements when the red or green signal lights were illuminated.

Similar results are seen in people with damage to the premotor cortex. Halsband and Freund ( 1990 ) found that patients with these lesions could learn to make six different movements in response to spatial cues but not to arbitrary visual cues. That is, they could learn to point to one of six locations in which they had just seen a visual stimulus, but they could not learn to use a set of visual, auditory, and tactile cues to make particular movements.

Nowak et al. ( 2009 ) found further evidence that the premotor cortex plays a role in learning to control movements in response to arbitrary stimuli. The investigators trained subjects to grasp and lift an object positioned between the thumb and forefinger of their right (dominant) hand. The subjects watched a computer screen; when a blue dot appeared, they immediately gripped the object and lifted it. Sometimes the dot was pale blue, and sometimes it was dark blue. The light blue dot indicated that the object would weigh 350 gm, and the dark blue dot indicated that it would weigh 550 gm. Thus, the force needed to grip and lift the object was indicated by an arbitrary signal. The subjects learned to grip the object more forcefully when the dark blue dot (heavy signal) appeared, indicating that the object would be heavy. Next, 20 sec of repetitive TMS was applied to the subjects’ left dorsal premotor cortex, which inhibits this brain region for approximately 30 min. When the subjects were again tested on the task, they did not adjust the force of their grip; instead, they used a more forceful grip regardless of the brightness of the blue dot.

Imitating and Comprehending Movements: Role of the Mirror Neuron System

Rizzolatti and his colleagues (Gallese et al., 1996 ; Rizzolatti et al., 2001 ; Rizzolatti and Sinigaglia, 2010 ) made some interesting observations that have changed the way we think about imitating and comprehending the behavior of others. The investigators found that neurons in an area of the rostral part of the ventral premotor cortex in the monkey brain (area F5) became active when monkeys saw people or other monkeys perform various grasping, holding, or manipulating movements with objects or when they performed these movements themselves. Thus, the neurons responded to either the sight or the execution of particular movements. The investigators named these cells mirror neurons . These neurons, located in the ventral premotor cortex, are reciprocally connected with neurons in the posterior parietal cortex, and further investigation found that this region also contains mirror neurons. Given the characteristics of mirror neurons, we might expect that they play a role in a monkey’s ability to imitate the movements of other monkeys—and Rizzolatti and his colleagues found that this inference was correct.

mirror neurons Neurons located in the ventral premotor cortex and inferior parietal lobule that respond when the individual makes a particular movement or sees another individual making that movement.

FIGURE 8.16 Important Motor Regions of the Human Brain

In the human brain, the inferior parietal lobule and the ventral premotor cortex constitute the primary mirror neuron circuit. The parietal reach region plays a role in reaching, and the anterior intraparietal sulcus plays a role in grasping.

Figure 8.16 shows the anatomy of the major regions of the parietal lobe of the human brain that I will discuss in the next several subsections of this chapter. (See Figure 8.16 . )

Several functional-imaging studies have shown that the human brain also contains a circuit of mirror neurons in the rostral part of the inferior parietal lobule (a region of the posterior parietal cortex) and the ventral premotor area. For example, in a functional imaging study, Buccino et al. ( 2004 ) had nonmusicians watch and then imitate video clips of an expert guitarist placing his fingers on the neck of a guitar to play a chord. Both watching and imitating the guitarist’s movements activated the mirror neuron circuit.

Several studies have found that the mirror neuron system is activated most strongly when one watches a behavior in which one is already competent. For example, Calvo-Merino et al. ( 2006 ) had professional ballet dancers watch videos of men or women perform ballet moves. Some moves are performed only by men, some only by women, and some by both men and women, but all of the moves have been seen many times by both male and female ballet dancers. The investigators found that when women watched women’s moves or when men watched men’s moves, the mirror neuron system was strongly activated. However, when women watched men’s moves or when men watched women’s moves, much less activity was seen in this circuit. Thus, the mirror neuron circuit develops sensitivity to the sight of movements that the person actually performs, not simply actions that the person has seen performed. Once this sensitivity develops, the circuit is activated by watching another person perform those movements.

Mirror neurons are activated not only by the performance of an action or the sight of someone else performing that action, but also by sounds that indicate the occurrence of a familiar action. For example, Kohler et al. ( 2002 ) found that mirror neurons in the ventral prefrontal cortex of monkeys became active when the animals heard sounds they recognized, such as a peanut breaking, a piece of paper being ripped, or a stick being dropped. Individual neurons—the researchers called them audiovisual neurons—responded to the sounds of particular actions and to the sight of those actions being performed. Presumably, activation of these neurons by these familiar sounds reminds the animals of the actions the sounds represent.

Haslinger et al. ( 2005 ) found that the interaction between audition and vision worked in the other direction as well. The investigators showed professional pianists silent videos of a hand playing the piano or making meaningless finger movements above a piano keyboard. (See Figure 8.17 . ) Functional imaging showed that when the subjects watched actual piano playing, the mirror neuron system and visual cortex were activated, as would be expected, but the auditory cortex was activated as well. Presumably, the musicians imagined what it was like to make the meaningful hand and finger movements, activating the mirror neuron system, but also imagined what the piano would sound like when the keys were pressed, activating the auditory cortex.

Rizzolatti, Fogassi, and Gallese ( 2001 ) suggest that the mirror neuron circuit helps us to understand the actions of others:

· [A]n action is understood when its observation causes the motor system of the observer to “resonate.” So, when we observe a hand grasping an apple, the same population of neurons that control the execution of grasping movements becomes active in the observer’s motor areas. . . . In other words, we understand an action because the motor representation of that action is activated in our brain. (p. 661)

FIGURE 8.17 Mirror Neurons in Musicians

Videos of piano playing, but not meaningless finger movements, activated the mirror neuron system and also the auditory cortex of professional pianists.

(From Haslinger, B., Erhard, P., Altenmüller, E., et al. Journal of Cognitive Neuroscience, 2005, 17, 282–293. Reprinted with permission.)

By “resonation,” Rizzolatti and his colleagues mean that the neural circuits responsible for performing a particular action are activated when we see someone else beginning to perform that action or even when we hear the characteristic sounds produced by that action. Feedback from the activation of these circuits gives rise to the recognition of the action.

The next time you intently watch someone executing a skilled action—say, pitching a baseball, swinging a bat, kicking a football, or jumping a hurdle—see whether you don’t find yourself tensing the muscles that you would use if you were performing the action. Presumably, the activation of the mirror neuron circuit is responsible for this effect. As we will see in Chapter 11 , we also tend to copy facial expressions of emotion that other people make, and feedback from doing so tends to evoke a similar emotional state in us.

A functional-imaging study by Iacoboni et al. ( 2005 ) suggests that the mirror neuron system helps us to understand other people’s intentions. The researchers showed subjects video clips of an arm and hand reaching for and grasping a drinking mug. The actions were shown in isolation or in the context of objects set out for a snack (mug, teapot, milk pitcher, sugar bowl, sealed jam jar, plate of cookies, and the like) or the same objects after the snack had been eaten (mug, milk pitcher overturned, cookies missing from the plate, open jam jar, and the like). The first context suggests that the intent of the action is that of drinking, and the second suggests that the intent is that of cleaning up. The investigators found that watching the reaching action activated the mirror neuron system of the ventral premotor cortex, but there were differences in the activation when the action occurred in the two different contexts. (There were no differences in the activation caused by simply looking at the contexts.) The authors concluded that the mirror neuron system encodes not only an action but the intent of that action. (See Figure 8.18 . )

Control of Reaching and Grasping

Much of our behavior involves interacting with objects in our environment. Many of these interactions involve reaching for something and then doing something with it, such as picking it up, moving it, or otherwise manipulating it. Researchers investigating these interactions classify them into two major categories: reaching and grasping. It turns out that different brain mechanisms are involved in these two activities.

FIGURE 8.18 Understanding Intentions

The photographs show the actions and contexts presented to the subjects in the experiment by Iacoboni et al. ( 2005 ).

(From Iacoboni, M., Molnar-Szakacs, I., Gallese, V., et al. PLoS Biology, 2005, 3, e79.)

FIGURE 8.19 The Parietal Reach Region

An inflated left cerebral hemisphere shows fMRI activation of the parietal reach region (PRR) just as people were about to make a pointing or reaching movement. POS = parieto-occipital sulcus.

(From Connolly, J.D., Andersen, R. A., and Goodale, M.A. Experimental Brain Research, 2003, 153, 140–145. Reprinted with permission.)

Most reaching behavior is controlled by vision. As we saw in Chapter 6 , the dorsal stream of the visual system is involved in determining the location of objects and, if they are moving, the direction and speed of their movement. You will not be surprised to learn that connections between the parietal lobe (the endpoint of the dorsal stream of the visual association cortex) and the frontal lobe play a critical role in reaching. As we saw in Chapter 6 , several regions of the visual association cortex are named for particular types of objects that we perceive, for example, fusiform face area, extrastriate body area, and parahippocampal place area. One region of the medial posterior parietal cortex has been named the parietal reach region . Connolly, Andersen, and Goodale ( 2003 ) found that when people were about to make a pointing or reaching movement to a particular location this region became active. Presumably, the parietal cortex determines the location of the target and supplies information about this location to motor mechanisms in the frontal cortex. (See Figure 8.19 and refer again to Figure 8.16 . )

parietal reach region A region in the medial posterior parietal cortex that plays a critical role in control of pointing or reaching with the hands.

Another region of the posterior parietal cortex, the anterior part of the intraparietal sulcus (aIPS), is involved in controlling hand and finger movements involved in grasping the target object. A functional-imaging study by Frey et al. (2004) had people reach for objects of different shapes, which required them to make a variety of hand and finger movements to hold onto the objects. The brain activity directly related to grasping movements was determined by subtracting the activity produced by reaching for and simply touching the objects from the activity produced by reaching for and grasping the objects. The grasping activity activated the aIPS. (See Figure 8.20 and refer again to Figures 8.16 and 8.19 . )

FIGURE 8.20 Activation of the Anterior Intraparietal Sulcus

The activation is produced by grasping movements made while reaching for objects with different shapes. Activity made by reaching for and simply touching the objects was subtracted from activity made by reaching and grasping, leaving only the grasping component of fMRI activation.

(From Frey, S. H., Vinton, D., Norlund, R., and Grafton, S. T. Cognitive Brain Research, 2005, 23, 397–405. Reprinted with permission.)

An experiment by Tunik, Frey, and Grafton ( 2005 ) confirmed the importance of the aIPS to grasping. The investigators had subjects reach for and grasp a rectangular object that was oriented with its long side in a vertical or horizontal position. On some trials (“perturbed trials”) the object suddenly rotated during the subjects’ reaching movements, which required the subjects to adjust the position of their hand or fingers before they reached the object. On some of these perturbed trials the investigators applied transcranial magnetic stimulation that disrupted the activity of the aIPS. When the disruptive stimulation occurred shortly after the rotation of the object, the subjects’ ability to accurately change grip posture was disrupted. Stimulation of the hand area of the primary motor cortex or other parts of the parietal lobe had no effect.

The visual input to the aIPS is, of course, from the dorsal stream of the visual system. In a functional-imaging study by Shmuelof and Zohary ( 2005 ), subjects watched brief videos of a hand reaching out to grasp a variety of objects. Sometimes the hand appeared in the left visual field and the object appeared in the right visual field; sometimes the locations for the hand and the object were reversed. (The subjects focused their gaze on a fixation point located between the hand and the object.) This procedure means that, for a particular trial, visual information about an object was transmitted to one side of the brain, and visual information about a hand shaped to grasp the object was transmitted to the other side of the brain. Analysis of the brain activation showed that information about the nature of the object activated the ventral stream (“what”) of the visual system and information about the shape of the hand activated the aIPS, which is part of the dorsal stream (“where”). The results suggest that the aIPS is involved in recognition of grasping movements as well as their execution.

Deficits of Skilled Movements: The Apraxias

Damage to the frontal or parietal cortex on the left side of the brain can produce a category of deficits called apraxia . Literally, the term means “without action,” but apraxia differs from paralysis or weakness that occurs when motor structures such as the precentral gyrus, basal ganglia, brain stem, or spinal cord are damaged. Apraxia refers to the inability to imitate movements or produce them in response to verbal instructions or inability to demonstrate the movements that would be made in using a familiar tool or utensil (Leiguarda and Marsden, 2000 ). Neuropsychological studies of the apraxias have provided information about the way skilled behaviors are organized and initiated.

apraxia Difficulty in carrying out purposeful movements, in the absence of paralysis or muscular weakness.

There are four major types of apraxia, two of which I will discuss in this chapter. Limb apraxia refers to problems with movements of the arms, hands, and fingers. Oral apraxia refers to problems with movements of the muscles used in speech. Apraxic agraphia refers to a particular type of writing deficit. Constructional apraxia refers to difficulty in drawing or constructing objects. Because of their relation to language, I will describe oral apraxia and the various forms of agraphia in Chapter 14 .

LIMB APRAXIA

Limb apraxia is characterized by movement of the wrong part of the limb, incorrect movement of the correct part, or correct movements but in the incorrect sequence. It is assessed by asking patients to perform movements—for example, imitating hand gestures made by the examiner. The most difficult movements involve pantomiming particular acts without the presence of the objects that are normally acted upon. For example, the examiner might say to the patient, “Pretend you have a key in your hand and open a door with it.” In response, a patient with limb apraxia might wave his wrist back and forth rather than rotating it or might rotate his wrist first and then pretend to insert the key. Or if asked to pretend that she is brushing her teeth, a patient might use her finger as though it were a toothbrush rather than pretending to hold a toothbrush in her hand.

To perform behaviors on verbal command without having a real object to manipulate, a person must comprehend the command and be able to imagine the missing article as well as to make the proper movements; therefore, these requests are the most difficult to carry out. Somewhat easier are tasks that involve imitating behaviors performed by the experimenter. Sometimes, a patient who cannot mime the use of a key can copy the examiner’s hand movements. The easiest tasks involve the actual use of objects. For example, the examiner might give the patient a door key and ask him or her to demonstrate its use. If the brain lesion makes it impossible for the patient to understand speech, then the examiner cannot assess the ability to perform behaviors on verbal command. In this case the examiner can only measure the patient’s ability to imitate movements or use actual objects. (See Heilman, Rothi, and Kertesz, 1983 , for a review.)

Why does damage to the left parietal hemisphere, but usually not the right, cause an apraxia of both hands? The answer seems to be that the right hemisphere is involved with extrapersonal space and the left hemisphere is involved with one’s own body. A functional-imaging study by Chaminade, Meltzoff, and Decety ( 2005 ) supports this explanation. The investigators asked subjects to watch another person perform hand and arm gestures and then either imitate the gestures or make different ones with the same arm or the other arm. On the basis of the activity seen by fMRI scans, the authors concluded that posterior regions of the right hemisphere tracked the movements of the model in space, while the left parietal lobe organized the movements that would be made in response.

Although the frontal and parietal lobes are both involved in the imitating hand gestures made by other people, the frontal cortex appears to play a more important role in recognizing the meaning of these gestures. Pazzaglia et al. ( 2008 ) tested patients with limb apraxia caused by damage to the left frontal or parietal lobes. They tested the patients’ recognition of hand gestures by having them watch video clips in which a person performed the gestures correctly or incorrectly. For example, incorrect gestures included playing a broom as if it were a guitar or pretending to hitchhike by extending the little finger instead of the thumb. Apraxic patients with damage to the inferior frontal gyrus, but not to the parietal cortex, showed deficits in comprehension of the gestures. (See Figure 8.21 . )

CONSTRUCTIONAL APRAXIA

Constructional apraxia is caused by lesions of the right hemisphere, particularly the right parietal lobe. People with this disorder do not have difficulty making most types of skilled movements with their arms and hands. They have no trouble using objects properly, imitating their use, or pretending to use them. However, they have trouble drawing pictures or assembling objects from elements such as toy building blocks.

constructional apraxia Difficulty in drawing pictures or diagrams or in making geometrical constructions of elements such as building blocks or sticks; caused by damage to the right parietal lobe.

FIGURE 8.21 Lesions Causing Limb Apraxia

Left hemisphere lesions in the frontal and parietal lobes cause limb apraxia. Lesions in red regions interfere with the ability of patients to comprehend the gestures made by other people.

(From Pazzaglia, M., Smania, N., Corato, E., and Aglioti, S. M. Journal of Neuroscience, 2008, 28, 3030–3041. Reprinted with permission.)

The primary deficit in constructional apraxia appears to involve the ability to perceive and imagine geometrical relations. Because of this deficit, a person cannot draw a picture, say, of a cube, because he or she cannot imagine what the lines and angles of a cube look like, not because of difficulty controlling the movements of his or her arm and hand. (See Figure 8.22 . ) Besides being unable to draw accurately, a person with constructional apraxia invariably has trouble with other tasks involving spatial perception, such as following a map.

The Basal Ganglia

ANATOMY AND FUNCTION

The basal ganglia constitute an important component of the motor system. We know that they are important because their destruction by disease or injury causes severe motor deficits. The motor nuclei of the basal ganglia include the caudate nucleus, putamen, and globus pallidus. The basal ganglia receive most of their input from all regions of the cerebral cortex (but especially the primary motor cortex and primary somatosensory cortex) and the substantia nigra. They have two primary outputs: the primary motor cortex, supplementary motor area, and premotor cortex (via the thalamus) and motor nuclei of the brain stem that contribute to the ventromedial pathways. Through these connections the basal ganglia influence movements under the control of the primary motor cortex and exert some direct control over the ventromedial system.

FIGURE 8.22 Constructional Apraxia

An attempt to copy a cube by a patient with constructional apraxia caused by a lesion of the right parietal lobe.

Figure 8.23(a) illustrates the components of the basal ganglia: the caudate nucleus , the putamen , and the globus pallidus . It also shows some nuclei associated with the basal ganglia: the ventral anterior nucleus and ventrolateral nucleus of the thalamus, the subthalamic nucleus , and the substantia nigra of the ventral midbrain. (See Figure 8.23a . )

caudate nucleus A telencephalic nucleus, one of the input nuclei of basal ganglia; involved with control of voluntary movement.

putamen A telencephalic nucleus; one of the input nuclei of the basal ganglia; involved with control of voluntary movement.

globus pallidus A telencephalic nucleus; the primary output nucleus of the basal ganglia; involved with control of voluntary movement.

ventral anterior nucleus (of thalamus) A thalamic nucleus that receives projections from the basal ganglia and sends projections to the motor cortex.

ventrolateral nucleus (of thalamus) A thalamic nucleus that receives projections from the basal ganglia and sends projections to the motor cortex.

subthalamic nucleus A nucleus located ventral to the thalamus, an important part of the subcortical motor system that includes the basal ganglia; a target of deep-brain stimulation for treatment of Parkinson’s disease.

Figure 8.23(b) shows some of the more important connections of the basal ganglia and helps to explain the role these structures play in the control of movement. For the sake of clarity this figure leaves out many connections, including inputs to the substantia nigra from the basal ganglia and other structures. First, let’s take a quick look at the loop formed between the cortex and the basal ganglia. The frontal, parietal, and temporal cortex send axons to the caudate nucleus and the putamen, which then connect with the globus pallidus. The globus pallidus sends information back to the motor cortex via the ventral anterior and ventrolateral nuclei of the thalamus, completing the loop. Thus, the basal ganglia can monitor somatosensory information and are informed of movements being planned and executed by the motor cortex. Using this information (and other information they receive from other parts of the brain), they can then influence the movements controlled by the motor cortex. Throughout this circuit, information is represented somatotopically. That is, projections from neurons in the motor cortex that cause movements in particular parts of the body project to particular parts of the putamen, and this segregation is maintained all the way back to the motor cortex. (See Figure 8.23b . ) Another important input to the basal ganglia comes from the substantia nigra of the midbrain. We saw in Chapter 4 that degeneration of the nigrostriatal bundle, the dopaminergic pathway from the substantia nigra to the caudate nucleus and putamen (the neostriatum), causes Parkinson’s disease. (I will say more about the neural circuits involved in this disorder in the next subsection.) (Look again at Figure 8.23b . )

Now let’s consider some of the complexities of the cortical–basal ganglia loop. The links in the loop are made by both excitatory (glutamate-secreting) neurons and inhibitory (GABA-secreting) neurons. The caudate nucleus and putamen receive excitatory input from the cerebral cortex. They send inhibitory axons to the external and internal divisions of the globus pallidus (the GPi and the GPe, respectively). The subthalamic nucleus also receives excitatory input from the cerebral cortex, and it sends excitatory input to the GPi. The pathway shown in solid lines that includes the GPi is known as the direct pathway . Neurons in GPi send inhibitory axons to the ventral anterior and ventrolateral thalamus (VA/VL thalamus), which send excitatory projections to the motor cortex. The net effect of the loop is excitatory because it contains two inhibitory links. Each inhibitory link (red arrow) reverses the sign of the input to that link. Thus, excitatory input to the caudate nucleus and putamen causes these structures to inhibitneurons in the GPi. This inhibition removes the inhibitory effect of the connections between the GPi on the VA/VL thalamus; in other words, neurons in the VA/VL thalamus become more excited. This excitation is passed on to the motor cortex, where it facilitates movements. (Look again at Figure 8.23b . )

direct pathway (in basal ganglia) The pathway that includes the caudate nucleus and putamen, the internal division of the globus pallidus, and the ventral anterior/ventrolateral thalamic nuclei; has an excitatory effect on movement.

FIGURE 8.23 Basal Ganglia

(a) The locations of the components of the basal ganglia and associated structures. (b) The major connections of the basal ganglia and associated structures. Excitatory connections are shown as black lines; inhibitory connections are shown as red lines. The direct pathway is indicated by arrows with solid lines. The indirect pathway is indicated by arrows with broken lines. The hyperdirect pathway is indicated by arrows with dotted lines. Many connections, such as the inputs to the substantia nigra, are omitted for clarity.

The pathway shown in broken lines, which includes the GPe, is known as the indirect pathway . Neurons in GPe send inhibitory input to the subthalamic nucleus, which sends excitatory input to the GPi. From there on, the circuit is identical to the one we just examined—except that the ultimate effect of this loop on the thalamus and frontal cortex is inhibitory. The globus pallidus also sends axons to various motor nuclei in the brain stem that contribute to the ventromedial system. The effect of this pathway is to inhibit the motor cortex. (Look once again at Figure 8.23b . )

indirect pathway (in basal ganglia) The pathway that includes the caudate nucleus and putamen, the external division of the globus pallidus, the subthalamic nucleus, the internal division of the globus pallidus, and the ventral anterior/ventrolateral thalamic nuclei; has an inhibitory effect on movement.

A third pathway is known as the hyperdirect pathway . Neurons in the pre-SMA send excitatory input to the subthalamic nucleus, which sends excitatory input to the GPi. As we just saw, the GPi has an inhibitory effect on the motor cortex, so the hyperdirect pathway inhibits movements. The general functions of the direct and indirect pathways have long been understood. However, the hyperdirect pathway was recognized much more recently (Nambu, Tokuno, and Takada, 2000; Gerfen, 2000 ). This pathway bypasses the caudate nucleus and putamen and is thus able to inhibit movement with a much shorter delay than the indirect pathway. Most investigators believe that this pathway plays a role in preventing or quickly stopping movements that are being initiated by the direct pathway (Nachev, Kennard, and Husain, 2008 ; Nambu, 2008 ). For example, suppose that you are jogging down a city street. As you approach a cross street, you see that the stoplight is red, so you stop running. The indirect pathway plays a role in the inhibition of your jogging. (Perhaps not completely—perhaps you jog in place while you wait for the light to change.) The light turns green, and this go signal is reflected by increased activity of your direct pathway. You lean forward and raise a foot to begin jogging again. Suddenly, you hear the roar of a speeding car immediately to your left. You quickly stop, and before you can turn you head to look for the source of the noise, a car that has just run through the red light passes in front of you. Activity in your hyperdirect pathway has just saved your life.

hyperdirect pathway An excitatory pathway from the pre-SMA to the subthalamic nucleus that increases the activity of the GPi and appears to play a role in preventing or quickly stopping movements that are being initiated by the direct pathway.

PARKINSON’S DISEASE

Now that you understand the roles played by the three cortical–basal ganglia loops, you can understand the symptoms and treatment of two important neurological disorders: Parkinson’s disease and Huntington’s disease. The primary symptoms of Parkinson’s disease are muscular rigidity, slowness of movement, a resting tremor, and postural instability. For example, once a person with Parkinson’s disease is seated, he or she finds it difficult to arise. Once the person begins walking, he or she has difficulty stopping. Thus, a person with Parkinson’s disease cannot easily pace back and forth across a room. Reaching for an object can be accurate, but the movement usually begins only after a considerable delay, and the individual components of the movement (a series of trunk, arm, hand, and finger movements) are poorly coordinated (Poizner et al., 2000 ). Writing is slow and labored, and as it progresses, the letters get smaller and smaller. Postural movements are impaired. A normal person who is bumped while standing will quickly move to restore balance—for example, by taking a step in the direction of the impending fall or by reaching out with the arms to grasp a piece of furniture. However, a person with Parkinson’s disease fails to do so and simply falls. A person with this disorder is even unlikely to put out his or her arms to break the fall.

Many of the symptoms I have just described can be explained as a deficiency of automatic, habitual responses (Redgrave et al., 2010 ). As we will see in Chapter 13 , the basal ganglia play an essential role in the learning and execution of automatic actions, as opposed to deliberate actions. For example, learning a complex skilled behavior such as driving a car requires thoughtful, deliberate actions. Someone who is driving a car for the first time will have to concentrate on what he or she is doing and will find that the demands of the task make it very difficult to carry on a conversation. However, the actions of an experienced driver are much more automatic, freeing up some brain resources to devote to a conversation or thoughts about the plans for that day. Disruption of the normal functions of the basal ganglia means that people with Parkinson’s disease have difficulty performing tasks automatically. As the disease progresses, they must “think through” actions that were previously automatic, which means that the actions become slower and demand more brain resources for their accomplishment.

Parkinson’s disease also produces a resting tremor—vibratory movements of the arms and hands that diminish somewhat when the individual makes purposeful movements. The tremor is accompanied by rigidity; the joints appear stiff. However, the tremor and rigidity are not the cause of the slow movements. In fact, some patients with Parkinson’s disease show extreme slowness of movements but little or no tremor.

Let’s look at Figure 8.23(b) again to see why damage to the nigrostriatal bundle causes slowness of movements and disrupts postural adjustments. Normal movements require an appropriate balance between the direct (excitatory) and indirect (inhibitory) pathways. The caudate nucleus and putamen consist of two different zones, both of which receive input from dopaminergic neurons of the substantia nigra. One of these zones contains D1 dopamine receptors, which produce excitatory effects. Neurons in this zone send their axons to the GPi. Neurons in the other zone contain D2 receptors, which produce inhibitory effects. These neurons send their axons to the GPe. (Look again at Figure 8.23b . ) The first of these circuits, beginning with the black arrow from the substantia nigra, goes through two inhibitory synapses (red arrows) before it reaches the VA/VL thalamus; thus, this circuit has an excitatory effect on behavior. The second of these circuits begins with an inhibitory input to the caudate nucleus and putamen, but it goes through four inhibitory synapses in the following pathway: substantia nigra → caudate/putamen → GPe → subthalamic nucleus → GPi → VA/VL thalamus. Thus, the effect of this pathway, too, is excitatory; thus, dopaminergic input to the caudate nucleus and putamen facilitate movements. Note that the GPi also sends axons to the ventromedial system. A decrease in this inhibitory output is probably responsible for the muscular rigidity and poor control of posture seen in Parkinson’s disease. (Refer again to Figure 8.23b . )

As we saw in Chapter 4 , the standard treatment for Parkinson’s disease is L-DOPA, the precursor of dopamine. When an increased amount of L-DOPA is present, the remaining nigrostriatal dopaminergic neurons in a patient with Parkinson’s disease will produce and release more dopamine. But this compensation often produces dyskinesias and dystonias—involuntary movements and postures that are presumably caused by too much stimulation of dopamine receptors in the basal ganglia. In addition, L-DOPA does not work indefinitely; eventually, the number of nigrostriatal dopaminergic neurons declines to such a low level that the symptoms become worse. Some patients—especially those whose symptoms began when they were relatively young—eventually become bedridden, scarcely able to move.

In recent years, clinicians have worked developing new ways to treat Parkinson’s disease, including stereotaxic surgery and implantation of stimulating electrodes in various regions of the basal ganglia. In addition, much research has been done on discovering the causes of the disease. I will describe these efforts in Chapter 15 .

HUNTINGTON’S DISEASE

Another basal ganglia disease, Huntington’s disease , is caused by degeneration of the caudate nucleus and putamen, especially of GABAergic and acetylcholinergic neurons. (See Figure 8.24 . ) Whereas Parkinson’s disease causes a poverty of movements, Huntington’s disease, formerly called Huntington’s chorea, causes uncontrollable ones, especially jerky limb movements. (The term chorea derives from the Greek khoros, meaning “dance.”) The movements of Huntington’s disease look like fragments of purposeful movements but occur involuntarily. This disease is progressive and eventually causes death.

Huntington’s disease A fatal inherited disorder that causes degeneration of the caudate nucleus and putamen; characterized by uncontrollable jerking movements, writhing movements, and dementia.

The symptoms of Huntington’s disease usually begin in the patient’s thirties or forties but can sometimes begin in the early twenties. The first signs of neural degeneration occur in the caudate nucleus and the putamen—specifically, in the medium-sized spiny inhibitory neurons whose axons travel to the external division of the globus pallidus. The loss of inhibition provided by these GABA-secreting neurons increases the activity of the GPe, which then inhibits the subthalamic nucleus. As a consequence, the activity level of the GPi decreases, and excessive movements occur. (Refer again to Figure 8.23b . ) As the disease progresses, the caudate nucleus and putamen degenerate until almost all of their neurons disappear. The patient dies from complications of immobility. Unfortunately, there is at present no effective treatment for this disorder.

FIGURE 8.24 Huntington’s Disease

(a) A slice through a normal human brain, showing the normal appearance of the caudate nuclei and putamen (arrowheads) and lateral ventricles. (b) A slice through the brain of a person who had Huntington’s disease. The arrowheads indicate the location of the caudate nuclei and putamen, which are severely degenerated. As a consequence of the degeneration, the lateral ventricles (open spaces in the middle of the slice) have enlarged.

(Courtesy of Harvard Medical School/Betty G. Martindale and Anthony D’Agostino, Good Samaritan Hospital, Portland, Oregon.)

Huntington’s disease is a hereditary disorder, caused by a dominant gene on chromosome 4. In fact, the gene has been located, and its defect has been identified as a repeated sequence of bases that code for the amino acid glutamine (Collaborative Research Group, 1993 ). This repeated sequence causes the gene product—a protein called huntingtin—to contain an elongated stretch of glutamine. Longer stretches of glutamine are associated with patients whose symptoms began at a younger age, which strongly suggests that this abnormal portion of the huntingtin molecule is responsible for the disease. Research on the role that abnormal huntingtin plays in death of basal ganglia neurons is described in Chapter 15 .

The Cerebellum

The cerebellum is an important part of the motor system. It contains about 50 billion neurons, compared to the approximately 22 billion neurons in the cerebral cortex. Its outputs project to every major motor structure of the brain. When it is damaged, people’s movements become jerky, erratic, and uncoordinated. The cerebellum consists of two hemispheres that contain several deep nuclei situated beneath the wrinkled and folded cerebellar cortex. Thus, the cerebellum resembles the cerebrum in miniature. The medial part of the cerebellum is phylogenetically older than the lateral part, and it participates in control of the ventromedial system. The flocculonodular lobe , located at the caudal end of the cerebellum, receives input from the vestibular system and projects axons to the vestibular nucleus. You will not be surprised to learn that this system is involved in postural reflexes. (See the green lines in Figure 8.25 . ) The vermis (“worm”), located on the midline, receives auditory and visual information from the tectum and cutaneous and kinesthetic information from the spinal cord. It sends its outputs to the fastigial nucleus (one of the set of deep cerebellar nuclei). Neurons in the fastigial nucleus send axons to the vestibular nucleus and to motor nuclei in the reticular formation. Thus, these neurons influence behavior through the vestibulospinal and reticulospinal tracts, two of the three ventromedial pathways. (See the blue lines in Figure 8.25 . )

flocculonodular lobe A region of the cerebellum; involved in control of postural reflexes.

vermis The portion of the cerebellum located at the midline; receives somatosensory information and helps to control the vestibulospinal and reticulospinal tracts through its connections with the fastigial nucleus.

fastigial nucleus A deep cerebellar nucleus; involved in the control of movement by the reticulospinal and vestibulospinal tracts.

The rest of the cerebellar cortex receives most of its input from the cerebral cortex, including the primary motor cortex and association cortex. This input is relayed to the cerebellar cortex through the pontine tegmental reticular nucleus. The intermediate zone of the cerebellar cortex projects to the interposed nuclei , which in turn project to the red nucleus. Thus, the intermediate zone influences the control of the rubrospinal system over movements of the arms and legs. The interposed nuclei also send outputs to the ventrolateral thalamic nucleus, which projects to the motor cortex. (See the red lines in Figure 8.25 . )

interposed nuclei A set of deep cerebellar nuclei; involved in the control of the rubrospinal system.

The lateral zone of the cerebellum is involved in the control of independent limb movements, especially rapid, skilled movements. Such movements are initiated by neurons in the frontal association cortex, which control neurons in the primary motor cortex. But although the frontal cortex can plan and initiate movements, it does not contain the neural circuitry needed to calculate the complex, closely timed sequences of muscular contractions that are needed for rapid, skilled movements. That task falls to the lateral zone of the cerebellum.

Both the frontal association cortex and the primary motor cortex send information about intended movements to the lateral zone of the cerebellum via the pontine nucleus . The lateral zone also receives information from the somatosensory system, which informs it about the current position and rate of movement of the limbs—information that is necessary for computing the details of a movement. When the cerebellum receives information that the motor cortex has begun to initiate a movement, it computes the contribution that various muscles will have to make to perform that movement. The results of this computation are sent to the dentate nucleus , another of the deep cerebellar nuclei. Neurons in the dentate nucleus pass the information on to the ventrolateral thalamus, which projects to the primary motor cortex. The projection from the ventrolateral thalamus to the primary motor cortex enables the cerebellum to modify the ongoing movement that was initiated by the frontal cortex. The lateral zone of the cerebellum also sends efferents to the red nucleus (again, via the dentate nucleus); thus, it helps to control independent limb movements through this system as well. (See Figure 8.26 . )

pontine nucleus A large nucleus in the pons that serves as an important source of input to the cerebellum.

dentate nucleus A deep cerebellar nucleus; involved in the control of rapid, skilled movements by the corticospinal and rubrospinal systems.

FIGURE 8.25 Inputs and Outputs of the Cerebellum

The figure shows the inputs and outputs of three systems: flocculonodular lobe (green lines), the vermis (blue lines), and the intermediate zone of the cerebellar cortex (red lines).

FIGURE 8.26 Inputs and Outputs of the Lateral Zone of the Cerebellar Cortex

The lateral zone receives information about impending movements from the frontal lobes and helps to smooth and integrate the movements through its connections to the primary motor cortex and red nucleus through the dentate nucleus and ventral thalamus.

In humans, lesions of different regions of the cerebellum produce different symptoms. Damage to the flocculonodular lobe or the vermis causes disturbances in posture and balance. Damage to the intermediate zone produces deficits in movements controlled by the rubrospinal system; the principal symptom of this damage is limb rigidity. Damage to the lateral zone causes weakness and decomposition of movement. For example, a person with this kind of damage who is attempting to bring the hand to the mouth will make separate movements of the joints of the shoulder, elbow, and wrist instead of performing simultaneous smooth movements.

Lesions of the lateral zone of the cerebellar cortex also appear to impair the timing of rapid ballisticmovements. Ballistic (literally, “throwing”) movements occur too fast to be modified by feedback. The sequence of muscular movements must then be programmed in advance, and the individual muscles must be activated at the proper times. You might like to try this common neurological test: Have a friend place his or her finger in front of your face, about three-quarters of an arm’s length away. While your friend slowly moves his or her finger around to serve as a moving target, alternately touch your nose and your friend’s finger as rapidly as you can. If your cerebellum is normal, you can successfully hit your nose and your friend’s finger without too much trouble. People with lateral cerebellar damage have great difficulty; they tend to miss the examiner’s hand and poke themselves in the eye. (I have often wondered why neurologists do not adopt a less dangerous test.)

When making rapid, aimed movements, we cannot rely on feedback to stop the movement when we reach the target. By the time we perceive that our finger has reached the proper place, it is too late to stop the movement, and we will overshoot the target if we try to stop it then. Instead of relying on feedback, the movement appears to be timed. We estimate the distance between our hand and the target, and our cerebellum calculates the amount of time that the muscles will have to be turned on. After the proper amount of time, the cerebellum briefly turns on antagonistic muscles to stop the movement. In fact, Kornhuber ( 1974 ) suggested that one of the primary functions of the cerebellum is timing the duration of rapid movements. Obviously, learning must play a role in controlling such movements.

Timmann, Watts, and Hore ( 1999 ) reported an interesting example of the role the cerebellum plays in timing sequences of muscular contractions. When tossing a ball at a target using an overarm throw, a person raises his or her hand above the shoulder, rotates the arm forward, and then releases the ball by extending the fingers—moving them apart. The timing of the release is critical: too soon and the ball goes too high, too late and it goes too low. The researchers found that normal subjects released the ball within an 11-msec window 95 percent of the time. Patients with cerebellar lesions did five times worse: Their window was 55 msec wide.

The cerebellum also appears to integrate successive sequences of movements that must be performed one after the other. For example, Holmes ( 1939 ) reported that one of his patients said, “The movements of my left arm are done subconsciously, but I have to think out each movement of the right [affected] arm. I come to a dead stop in turning and have to think before I start again.” Thach ( 1978 ) obtained experimental evidence that corroborates this role. He found that many neurons in the dentate nuclei (which receive inputs from the lateral zone of the cerebellar cortex) showed response patterns that predicted the next movement in a sequence rather than the one that was currently taking place. Presumably, the cerebellum was planning these movements.

Dr. S., a professor of neurology at the medical school, stood on the stage of the auditorium as he presented a case to a group of physicians and students. He discussed the symptoms and possible causes of cerebellar–brain stem degeneration. “Now I’d like to present Mr. P.,” he said, as a set of MRI scans appeared on the screen. “As you can see, Mr. P.’s cerebellum shows substantial degeneration, but we can’t see evidence of any damage to the brain stem.”

Dr. S. left the stage and returned, pushing Mr. P. onstage in a wheelchair.

“Mr. P., how are you feeling today?”

“I’m fine,” he replied. “Of course, I’d feel better if I could have walked out here myself.”

“Of course.”

Dr. S. chatted with Mr. P. for a few minutes, getting him to talk enough so that we could see that his mental condition was lucid and that he had no obvious speech or memory problems.

“Okay, Mr. P., I’d like you to make some movements.” He faced Mr. P. and said, “Please stretch your hands out and hold them like this.” Dr. S. suddenly raised his arms from his sides and held them out straight in front of him, palms down, fingers pointing forward.

Mr. P. did not respond immediately. He looked as if he were considering what to do. Suddenly, his arms straightened out and lifted from the armrests of the wheelchair. Instead of stopping when they were pointed straight ahead of him, they continued upward. Mr. P. grunted, and his arms began flailing around—up, down, left, and right—until he finally managed to hold them outstretched in front of him. He was panting with the effort to hold them there.

“Thank you, Mr. P. Please put your arms down again. Now try this.” Dr. S. very slowly raised his arms from his side until they were straight out in front of them. Mr. P. did the same, and this time there was no overshoot.

After a few more demonstrations, Dr. S. thanked Mr. P. and wheeled him offstage. When he returned, he reviewed what we had seen.

“When Mr. P. tried to quickly raise his arms in front of him, his primary motor cortex sent messages to the appropriate muscles, and his arms straightened out and began to rise. Normally, the cerebellum is informed about the movement and, through its connections back to the motor cortex, begins to contract the antagonistic muscles at the appropriate time, bringing the arms to rest in the intended position. Mr. P. could get the movement started just fine, but the damage to his cerebellum eliminated the help this structure gives to rapid movements, and he couldn’t stop his arms in time. When he tried to move slowly, he could use visual and kinesthetic feedback from the position of his arms to control the movement.”

The Reticular Formation

The reticular formation consists of a large number of nuclei located in the core of the medulla, pons, and midbrain. The reticular formation controls the activity of the gamma motor system and hence regulates muscle tonus. In addition, the pons and medulla contain several nuclei with specific motor functions. For example, different locations in the medulla control automatic or semiautomatic responses such as respiration, sneezing, coughing, and vomiting. As we saw, the ventromedial pathways originate in the superior colliculi, vestibular nuclei, and reticular formation. Thus, the reticular formation plays a role in the control of posture.

The reticular formation also plays a role in locomotion. Stimulation of the mesencephalic locomotor region , located ventral to the inferior colliculus, causes a cat to make pacing movements (Shik and Orlovsky, 1976 ). The mesencephalic locomotor region does not send fibers directly to the spinal cord but apparently controls the activity of reticulospinal tract neurons.

mesencephalic locomotor region A region of the reticular formation of the midbrain whose stimulation causes alternating movements of the limbs normally seen during locomotion.

The reticular formation also appears to exert control over some very specific behaviors. For example, Siegel and McGinty ( 1977 ) recorded from thirty-five single neurons in the reticular formation of unanesthetized, freely moving cats. Thirty-two of these neurons responded during specific movements of the head, tongue, facial muscles, ears, forepaw, or shoulder. The specific nature of the relationships suggests that the neurons play some role in controlling the movements. For example, one neuron responded when the tongue moved out and to the left. The functions of these neurons and the range of movements they control are not yet known.

SECTION SUMMARY: Control of Movement by the Brain

The motor systems of the brain are complex. (Having read this section, you do not need me to tell you that.) A good way to review the systems is through an example. Suppose you see, out of the corner of your eye, that something is moving. You quickly turn your head and eyes toward the source of the movement and discover that a vase of flowers on a table someone has just bumped is ready to fall. You quickly reach forward, grab it, and restore it to a stable, upright position. (For simplicity’s sake I will assume that you are right-handed.)

The rapid movement of your head and eyes is controlled by mechanisms that involve the superior colliculi and nearby nuclei. The head movement and corresponding movement of the trunk are mediated by the tectospinal tract. You perceive the tipping vase because of the activity of neurons in your visual association cortex. The dorsal stream of your visual association cortex also contributes spatial information to the parietal reaching region in your left hemisphere, which calculates the reaching movement you must make and transmits this information to the motor association cortex in your left frontal lobe. During your reaching movement the cortex located in your anterior intraparietal sulcus sends information to your motor association cortex that moves your hand and fingers so that you will be ready to grasp the falling vase. Because the movement will have to be very rapid, your cerebellum controls its timing on the basis of information it receives from the association cortex of the frontal and parietal lobes. Your hand stops just as it touches the vase, and connections between the somatosensory cortex and the primary motor cortex initiate a reflex that closes your hand around the vase.

The muscles of your arm and hand are controlled through a cooperation between the corticospinal, rubrospinal, and ventromedial pathways. Even before your hand moves, the ventral corticospinal tract and the ventromedial pathways (vestibulospinal and reticulospinal system, largely under the influence of the basal ganglia) begin adjusting your posture so that you will not fall forward when you suddenly reach in front of you. Depending on how far forward you will have to reach, the reticulospinal tract may even cause one leg to step forward to take your weight. The rubrospinal tract controls the muscles of your upper arm, and the lateral corticospinal tract controls your finger and hand movements. Perhaps you say, triumphantly, “I got it!” The corticobulbar pathway, under the control of speech mechanisms in the left hemisphere, causes the muscles of your vocal apparatus to say these words.

The supplementary motor area (SMA) and the premotor cortex receive information from the parietal lobe and help to initiate movements through their connections with the primary motor cortex. The SMA is involved in well-learned behavioral sequences. Neurons there fire at particular points in behavioral sequences, and disruption or damage impairs the ability to perform these sequences. The pre-SMA is involved in awareness of our decisions to make spontaneous movements. The premotor cortex is involved in learning and executing complex movements that are guided by arbitrary sensory information, such as verbal instructions. This region and the inferior parietal lobule constitute a mirror neuron system that plays an important role in imitation and understanding the actions and intentions of others.

A person with apraxia will have difficulty making controlled movements of the limb in response to a verbal request or an attempt to imitate another person’s action. Most cases of apraxia are produced by lesions of the left frontal or parietal cortex. The left parietal cortex directly controls movement of the right limb by activating neurons in the left primary motor cortex and indirectly controls movement of the left limb by sending information to the right frontal association cortex.

The basal ganglia are part of a circuit that includes the cerebral cortex, the subthalamic nucleus, thalamic motor nuclei, and the substantia nigra. The direct pathway is involved in excitation of cortical mechanisms of motor control, and the indirect and hyperdirect pathways are involved in the inhibition of these mechanisms. Parkinson’s disease is caused by degeneration of dopamine-secreting neurons of the substantia nigra that send axons to the basal ganglia. An important symptom of this disorder is disruption of automatic behaviors. Huntington’s disease, a fatal disease caused by a mutation that caused production of abnormal huntingtin protein, causes degeneration of the caudate nucleus and putamen. Although identification of the faulty protein provides hope for understanding the causes of the neural degeneration, there is still no treatment for this disorder.

▪ THOUGHT QUESTION

Think about the kinds of automatic and deliberate actions you take in the course of a day. Which of these actions do you think would be impaired if you had Parkinson’s disease? Explain why.

Review Questions

Study and Review on MyPsychLab

Describe the three types of muscles found in the bodies of mammals and explain the physical basis of muscular contraction.

Explain the monosynaptic stretch reflex, the gamma motor system, and the contribution of the Golgi tendon organ.

Describe the organization of motor cortex and the role of the motor cortex in initiating, imitating, and comprehending movements.

Describe the four principal motor tracts and the movements they control.

Describe the symptoms and causes of limb apraxia and constructional apraxia.

Discuss the anatomy and function of the basal ganglia and its role in Parkinson’s disease and Huntington’s disease.

Discuss the role of the cerebellum and the reticular formation in the control of movement.

Explore the Virtual Brain in MyPsychLab

▪ CONTROL OF MOVEMENT BY THE BRAIN

Although we often take movement for granted, the neural regulation of movement involves many brain regions. The Control of Movement by the Brain module of the virtual brain shows the brain regions and circuits involved in planning, executing, sensing, and coordinating movement.