The motor systems can be divided into several interconnected parts. The spinal cord contains primary motor neurons and premotor interneurons that form the basis for spinal reflexes and basic motor patterns, which in turn are modulated by descending supraspinal pathways: the pyramidal tract and the extrapyramidal descending fibers. The pyramidal system, which carries impulses from the cortical motor fields to the primary motor neurons and their related interneurons, is especially important for the control of finely tuned voluntary movements, as exemplified by delicate finger movements.
The functions of the corticospinal tract is superimposed on the control exerted by the descending brainstem pathways, which- originate in many parts of the reticular formation, the vestibular nuclei and some midbrain areas. All movements are influenced by these pathways, which are also of special importance for the regulation of muscle tone and the maintenance of erect posture.
Two other brain structures, ie. the cerebellum and basalganglia, are crucially important for motor functions. Part of the activity generated in the cerebellum and basal ganglia is channeled through the brainstem descending pathways. In addition, both structures form key elements in two parallel, reentrant systems, which return their influences to the cortex through discrete and separate portions of the ventrolateral thalamus.
Several telencephalic structures,including some parts of the amygdaloid body, the ventral components of the basal ganglia and some hypothalamic areas, form a highly integrated system, which is especially concerned with emotional and motivational states have also direct access to brainstem areas controlling primary motor neurons.
During most movements, the motor centers need constant information from receptors in muscles, around joints and in the skin about whether the movement is progressing in accordance with plan. Often visual information is also crucial for the proper execution of movements. In addition, impulses from many other parts of the brain are necessary for movement, for example, those involved in the early stages of movement planning and in the mediation of motivated behavior.
Classification of Movements
As a rule most automatic movements require only the use of relatively simple reflex arcs at the spinal level (like the retraction of the arm from a noxious stimuli). Somewhat less automatic and more complex movements such as ventillation, locomotion and postural control depend, in addition on the participation of neural groups in the brain stem. Such movements do not require our attention directed toward them but can also be subjected to voluntary control. The least automatic movements are precision grips with the fingers and delicate manipulatory or exploratory movements such as writing, drawing, playing an instrument. Equally precise voluntary control exists for the muscles of the larynx, the tongue and some of the facial muscles. These movements depend on the participation of the cerebral cortex to coordinate and control the activity of motor centers in the brain stem and spinal cord. The degree to which a movement is automatic changes with learning.
The Peripheral Motor Neuron
The motor neurons, whose axons project to the striated muscles, are often referred to as the primary or lower motor neurons (LMN). These neurons are located in the ventral horns of the spinal cord and in some of the cranial nerve nuclei, and they represent the "final common path" for all impulses to the striated muscles. The large motor neurons that innervate the striated muscles are referred as alfa motor neurons. Scattered among the large motor neurons are many small neurons called gamma neurons, they send their axons to intrafusal muscle fibers of the muscle spindles.
Topography of motor neuronal cell groups. The spinal motor neuronal cell groups, which together form Rexed's lamina IX, are located according to a general somatotopic pattern. The somatotopic organization of motor neurons is important for understanding the relationship between the descending supraspinal pathways and various motor neuron pools.
The neurons that supply the axial musculature, including the neck muscles, are located ventromedially, whereas the neurons for the musculature of the limbs are situated in the lateral part of the ventral horn. The ventromedial cell column is present throughout the spinal cord. The lateral cell groups, however, are present only in the enlargements, and they can in turn be divided into three divisions: a central, ventrolateral and dorsolateral column. The central column innervates the girdle muscles, the ventrolateral column innervates the proximal limb muscles, and the dorsolateral column supplies the distal limb muscles.
The Motor end-plate, motor units. The axon of a motor neuron arborizes extensively to supply many muscle fibers. The motor neuron, together with the muscle fibers it supplies, is called a motor unit. Muscles used for delicate movements, like the hand muscles, have small motor units in the sense that one motor neuron may supply less than 100 muscle fibers; the eye muscles have even smaller motor units. The junction between the terminal branches of the axon and the muscle fiber, i.e. the neuromuscular junction, is known as the motor end-plate. When the action potential reaches the end-plate, acetylcholine is released into the synaptic cleft. The transmitter binds to specific receptors on the muscle cell membrane, thereby producing an excitatory postsynaptic potential, i.e. the end-plate potential. This triggers an action potential in the muscle fiber, which results in contraction of its myofibrils.
Premotor neurons and proriospinal neurons. Most of the boutons that impinge on the alpha and gamma motor neurons belong to interneurons, which are distributed in lamina VII. The interneurons participate in polysynaptic spinal reflexes, and many of the motor commands that reach the motor neurons through the descending supraspinal pathways are being mediated by interneurons. Circuits of interneurons also form specialized pattern generators for rhythmic movements in activities like locomotion. Propriospinal neurons project through the fasciculi proprii to other segments of the spinal cord. They form the anatomical basis for intersegmental coordination of various muscles in movement synergies.
Central pattern generators. Based on mutual interrelations and specific connections with motor neurons, certain populations of interneurons take on a special significance in the sense that they form highly sophisticated circuits, which are connected in a specific pattern to flexor and extensor motor neurons, and which are capable of facilitating and sustaining coordinated locomotor activities and rhythmic movements if properly activated. The central pattern generattor can be regarded as a central framework for stereotyped locomotor movements. In human, such spinal locomotor circuit cannot generate rhythmic movements, e.g. walking, in the absence of supraspinal control. However, in response to commands and modulatory influences reaching the spinal cord from the periphery and through the supraspinal descending pathways, the locomotor generators are able to carry out many of the detailed and complicated neuronal interactions, which are the prerequisite for the highly coordinated rhythmic movements that characterize locomotion.
Central Motor Pathways The Pyramidal Tract. In primates, including humans, cortical neurons with axons projecting to the spinal cord are found most densely in the anterior bank of the central sulcus. The density of such neurons decreases from there rostrally to the posterior bank of the arcuate sulcus and medially to the cingulate sulcus. After crossing at the medullary-spinal junction, as descending corticospinal axons reach their target levels in the spinal cord, they enter the spinal gray matter, where they ramify and synapse. A small fraction of these axons synapse directly on motor neurons in Rexed’s lamina IX. Most of the corticospinal neurons that make such monosynaptic connections to motor neurons have their somata in the anterior bank of the central sulcus, in the portions of the somatotopic map that corresponds to the hands and feet. These monosynaptic connections are generally made on the motor neurons of distal limb muscles, whose somata are clustered in the dorsolateral ventral horn. Corticospinal axons from neurons located farther anteriorly to the central sulcus typically synapse on premotor interneurons in the intermediate zone and ventromedial portion of the ventral horn (Rexed VII and VIII), where the motor neurons of proximal limb muscles and axial muscles are located. These axons constitute the vast majority of corticospinal axons. Some of them cross the midline to reach the ventromedial ventral horn ipsilateral to their origin; such doubly decussating corticospinal axons, along with the uncrossed ventral corticospinal tract, maybe partly responsible for the relative preservation of trunk and proximal limb movements after unilateral damage to the cortex.
The Rubrospinal Tract. Neurons of cortical area 4 and 6 can influence spinal motor neurons indirectly through synaptic relays in the red nucleus. The cortciorubrospinal projections, together with the direct corticospinal system, control fine movements of the distal extremities, while the more medial corticoreticulospinal system (below) contrals walking and postural movements.
The Tectospinal Tract (TSp) The TSp tract is of particular important for movements of the head and eyes as part of the optic reflexes. It is a crossed pathway and terminate on medially located interneurons of the intermediate zone.
Vestibulospinal Tracts (VSp). Like the rubrospinal fibers, the VSp ones act primarily on medial motor neurons (axial musculature and proximal muscles; antigravity muscles). The medial vestibulospinal tract takes its origin from the medial vestibular nucleus and descends bilaterally in the medial longitudinal bundle to terminate in the cervical cord. The lateral vestibulospinal tract, which arises from the lateral vestibular nucleus is an uncrossed pathway and terminate all levels of the cord. Their primary importance is to mediate reflex head movements in response to vestibular stimuli. The vestibular nuclei do not receive afferents from the cerebral cortex. The VSp neurones are therefore more independent and mediate primarily automatic reflex movements and adjustments of muscle tone.
Control of Voluntary Movements Control of voluntary movement involves much of the cerebral cortex anterior to the central sulcus. In addition to the classically described primary motor cortex (M1) and supplementary motor area (SMA), a number of separately identifiable motor areas are found in the premotor cortex anterior to M1 and the SMA and in the cingulate sulcus inferior to SMA. These cortical areas are connected with one another and receive input from prefrontal and parietal cortical areas as well as from the basal ganglia and cerebellum via the thalamus. Generation of a voluntary movement involves neuronal activity in somatotopically organized regions of the cortical motor areas. The discharge of M1 neurons transmits information on features of movement including direction, force, rate of change of force, joint position, and velocity. The discharge of any single M1 neuron may contain only broadly tuned information on one or more kinematic and dynamic parameters, but the ensemble discharge of a large population of M1 neurons provides an accurate representation of movement parameters. The non-primary motor cortical areas also participate of some kinematic and dynamic movement parameters. The non-primary motor areas appear more specialized, however, for selecting and controlling movements made in particular behavioral contexts, such as when the direction of a movement to be made must be remembered or when a movement must be selected on the basis of available visual cues.
Primary Motor Cortex (M1) here the threshold for eliciting movements by electrical stimulation is lower than in any other part of the cortex. M1 receives its main afferents from S1 (3,1,2), area 5,6, in addition from VL. Many of the pyramidal tract fibers originate in M1. On the other hand, many efferents from M1 reach other cortical and subcortical areas involved in motor control, such as the red nucleus, the RF, the basal ganglia and brain stem nuclei that project to the cerebellum. Nevertheless, the movements evoked by very weak electrical stimulation of the motor cortex are mediated by the pyramidal tract. Such movements occur in the opposite body half and can be limited to a few muscles in distal parts of the extremities and the face. With increasing stimulus strength, more muscles are recruited, and also more proximal ones. Disproportionally large part of M1 is devoted to the control of the hand and the lips and tongue. M1 is probable instrumental initiating the movement, but the decision to initiate a particular movement is not made in M1.
In normal humans who are actively practicing a complex sequence of finger movements, the cortical territory representing a given finger muscle enlarges as the subject become skilled at performing the sequence. This ability of M1 to reorganize may in part underlie motor recovery seen in humans after damage to M1 or the corticospinal tract. M1 appears to control the number of muscles, direction of movement, movement forces, the position of a particular joint, or the velocity of movement. However, neurons in several non-primary cortical motor areas may participate with those in M1 to control movement parameters such as direction, force, position and velocity. Any given parameter or other feature of a movement is probably represented not by the discharge of a single M1 neuron, but by the ensemble activity of a distributed population of cortical neurons.
Cortical areas outside the primary motor cortex seem to be especially concerned with using a wide variety of sensory and other information as ‘cues’ to trigger and guide movements. Further insight into the cortical processes controlling movement has been obtained by separating in time the instruction to move from the trigger to execute the instruction. (instruction delay period, set related activity). Such set related activity is more common in PM and SMA than in M1, where activity during movement execution predominates. During the delay between instruction and trigger, PM, SMA appear to store information on the direction of the impending movement, rather than about the cues. Area principalis neurons also show delay related activity in spatial delay tasks.
Another aspect of movement preparation that differentially involves certain motor areas has to do with whether the instructions about what to do come from internally remembered or externally delivered cues. Whereas neurons in M1 showed similar discharge rates during the internally remembered and externally cued trials for a given sequence, SMA neurons were generally more active during the internally remembered trials, and PM neurons were active during externally cued trials. Lesion studies also indicate that the SMA is particularly involved when a movement is based on internally stored information, whereas the PM is particularly involved when a movement is based on available visual cues. Some studies also suggest that neural activity in cortical motor areas dependent on certain behavior context. For example, Rizzolatti et al. have shown that F5 (PMv) has an important function when the hands are used in particular configurations. Some F5 neurons discharge vigorously during a power grasp with the whole hand but not during a delicate pinch. Especially intriguing is the observation that F5 neurons that discharge during a particular type of hand movement may also discharge as the monkey watches a human perform a similar hand movement.
The Supplementary Motor Area (SMA) The neural activity increase in the SMA especially in relation to complex movements. Increased activity in the SMA is not related to the movement itself, since it is sufficient that the person imagines the goal directed performance of a fairly complex movement. In such case there is no increase of activity in M1. Recording of single-cell activity in the SMA has shown that many cells change their activity in relation to sensory stimulus (light, passive movements, etc) that the animal knows is signal to start a certain voluntary movement. The SMA is important for organizing and planning fairly complex movements and for mediating an appropriate motor response to sensory stimuli.
The Premotor Cortex (PM) occupies the largest part of area 6. This region probably sends fewer fibers to the spinal cord than SMA but has strong connections with the RF, red nucleus, basal ganglia. It has important projection to M1. The PM is important for the control of visually guided movements, such as the proper orientation of the hand and fingers when they approach an object to be grasped. After damage to the M1, the handling of an object is clumsy and insecure, but the ability to avoid an obstacle is not lost. Connections from the extrastriate areas in the occipital lobe to the PM are necessary for the ability to perform such goal directed movements. In agreement with the above observations, single-cell recordings show that many cells in the PM change their activity about 60 msec after a light signal that the monkey is trained to respond to with a certain movement.
In the acute stage after a stroke, patients with lesions of the SMA reach out and grasp objects with the affected arm, even when they have been told to refrain from moving. This alien hand syndrome reflects a dominance of externally guided lateral PM pathways. The sight of an object within reaching distance evokes a motor plan to grasp an object. We usually can inhibit movement if we are instructed to do so or if the movement is inappropriate. But when internal control sources are removed, the movement can be triggered by appropriate external stimulus.
Posterior Parietal Cortex. Many neurons are active in relation to movements in the posterior parietal cortex (area 5, 7). One kind of neuron is active before goal-directed, reaching movements, such as when a monkey stretches its hand toward a banana. Such neurons do not become active, however, in relation to movement in the same direction but without a specific aim, or in relation to a passive movement. Other kinds of neurons increase their activity in relation to exploratory hand movements, such as when a monkey studies a foreign object. In area 7, some neurons increase their activity only when the monkey stretches the hand toward an object that it also looks at. In humans, lesions of the posterior parietal cortex may, for example, make them unable to open a door or to handle previously familiar tools. Such persons also have difficulties with proper orientation of the hand with relation to an object, and they easily miss an object even though they see it clearly. This kind of symptom is called apraxia.
Recent studies, using both single-cell recordings with primates and brain imaging techniques suggest that parallel circuits may be involved in motor planning. One circuit, including the parietal lobe, lateral premotor and cerebellar pathways is essential for producing spatially directed or guided movements. These regions are active during the early stages of skill acquisition. A second circuit, associated with the SMA, basal ganglia and perhaps the temporal lobe, becomes more dominant as the skill is well learned and driven by the internal representation of the desired action. Both circuits converge on the motor cortex, the primary link between the cortex and limbs for voluntary movements.
MONKEY MOTOR CORTEX
Using multiple criteria, including cytoarchitectonic, connectional, neurochemical and functional, a well accepted parcellation of the motor cortex in monkeys was proposed by Matelli et al (Matelli et al., 2004).(Fig and Table in the doc for comparison with Broadmann’s nomenclature). Accordingly, the motor cortex is a mosaic of at least seven distinct areas that contains a multiplicity of body movement representations, each playing a different role in motor control. If the general pattern of connectivity is considered, the various frontal motor areas can be grouped into two major classes: the caudal motor areas (F1-F5) that receive a primary cortical input from the parietal lobe and the rostral areas F6-F7 that receive their primary cortical input from the prefrontal cortex. The organization of the corticospinal projection is in agreement with the subdivision of the motor areas in two classes: corticospinal projections originate from F1-F5. In contrast, the organization of the prefronto-dependent motor areas do not project to the spinal cord, but their descending input terminates in various brainstem areas. Also, F6-F7 areas are not connected to F1, indicating that these areas cannot control movement directly.
To understand and represent the space around our bodies, we must put together vision, touch and proprioception, as well as vestibular sensation and audition. These signals are initially combined in the parietal lobe. The parietal areas also appear to begin the process of planning and coordination of movements. Different parietal areas are specialized for different motor outputs, such as those for eye, arm and hand movements. These parietal areas project to premotor areas in the frontal lobe, in which the processing of space and movement continues. In particular, area PMv appear to represent the space immediately surrounding the face, arms, and upper torso in body-part-centered coordinates. These body-part-centered coordinates can provide a general mechanism for guiding movements of the limbs and head toward, away from or around the everyday objects that surrounds us.
Neurons in the ventral premotor cortex (F5) of the monkey encode the locations of visual, tactile, auditory and remembered stimuli. Some of these neurons encode the locations of stimuli with respect to the arm, and may be useful for guiding movements of the arm. Others encode the locations of stimuli with respect to the head, and may be useful for guiding movements of the head. Charles Gross and colleagues’ studies suggest that a general principle of sensory-motor integration is that space surrounding the body is represented in body-part-centered coordinates. That is, there are multiple coordinate systems used to guide movement, each one attached to a different part of the body. Evidence from both human and monkey studies suggest that the formation of spatial maps in the brain and the guidance of limb and body movements do not proceed in separate stages but are closely integrated in both the parietal and frontal lobes.
Regions (area 7a) in the parietal lobe receive convergent visual, tactile, proprioceptive and efference copy input. These neurons carry the raw information necessary for other brain areas to construct spatial coordinate systems. The neuron properties in VIP and 7b are somewhat similar to those in PMv. As in PMv, a high percentage of neurons in VIP and 7b are bimodal, visual and tactile, and the visual receptive fields are generally restricted to the space near the body. However, the visual receptive fields are not as closely linked to the body surface as in PMv. In 7b, for bimodal cells with a tactile response on the arm, the visual receptive fields do not move when the arm is moved. In VIP, only a small proportion of the visual receptive fields do not move when the eyes move. These two areas would therefore seem to form a processing stage immediately before the body-part-centered visual receptive fields in PMv.
Another route by which spatial information might reach premotor cortex and guide movement is through PO-MIP-PMd. It is possible that PMd is specific for projecting the hand toward the target, while PMv controls greater range of spatially guided movements involving the arms, chest and head.
In the traditional view, the parietal lobe contains a general-purpose map of the visual space, and this spatial information is then relayed to the motor areas of the frontal lobe to guide behavior. However, the planning and coordination of movement appear to begin in the parietal lobe itself. These motor-specific parietal areas project to corresponding specific premotor areas in the frontal lobe. The premotor areas are, however, where the final spatial maps for guiding movements are constructed.
Grasping objects: The cortical mechanisms of visuomotor transformation
Grasping requires coding of the object’s intrinsic properties (size and shape), and the transformation of these properties into a pattern of distal (finger and wrist) movements. In monkeys, the transformation of an object’s intrinsic properties into specific grips takes place in a circuit that is formed by the inferior parietal lobule and the inferior premotor area (area F5). Neurons in both these areas code size, shape and orientation of objects, and specific types of grip that are necessary to grasp them. Grasping movements are coded more globally in the inferior parietal lobule, whereas they are more segmented in area F5. In humans, neuropsychological studies of patients with lesions to the parietal lobule confirm that primitive shape characteristics of an object for grasping are analyzed in the parietal lobe, and also demonstrate that this ‘pragmatic’ analysis of objects is separated from the semantic analysis performed in the temporal lobe.
Correct execution of grasping requires the integrity of primary motor cortex (Bodmann area 4, or F1). Lesion of this area in primates, as well as damage to the pyramidal tract, produces a profound deficit in the control of individual fingers, and consequently a disruption of normal grasping. Direct access of visual information that is needed for hand shaping, however, is limited in F1, where visually responsive neurons are rare. Intracortical microstimulation studies showed that F5 is related specifically to grasping movements. Two types of visual responses were observed in F5 related to grasping movements. Neurons of the first type respond to presentation of graspable objects. Neurons of the second type (mirror neurons) respond when the monkey sees movements, similar to those that are coded by the neuron but that are executed by the experimenter or another monkey. F5 projects to F1. Monkeys with lesions in the inferior parietal lobule typically present misreaching with the contralesional arm. In addition, their contarlesional hand fails to shape, and makes awkward grasps. Neurons that are involved in hand movement were found to be concentrated in anterior intraparietal area that is connected to F5. These neurons were selectively activated during grasping or fixation. Some of them were also sensitive to the size or the orientation of the objects. Most of the parietal neurons appear to represent the entire action, since they start to discharge with the hand shaping, and continue to fire while the monkey is holding the object. This property contrasts with those of F5 neurons, which were related commonly to a particular segment of action. Indeed, in M1, on which F5 projects heavily, neurons code even more fragmental movements.
HEMIPLEGIA Hemiplegia, the loss of voluntary movements on the contralateral side of the body, most frequently results from a hemorrhage in the middle cerebral artery. A person might wake up with severe headache or experience a sudden loss of consciousness, and notice a complete loss of control in one limb. The loss of movement is most evident in the distal effectors. Symptoms: 1) areflexia (reflexes are absent immediately after a stroke); 2) hyperreflexia (within a couple of weeks the reflexes return and even became hyperactive; 3) spastic muscles (the spasticity is most pronounced in the antigravity muscles); 4) appearance of pathologic reflexes (Babinski’s, etc) Lesion of the motor cortex affect the corticopsinal and extrapyramidal tracts. The loss of control over individual joints and distal extremities is attributed to damage in the cortico-spinal tract. Spasticity and hyperreflexia are attributed to changes in the extrapyramidal system. When the cortical influence is removed, these more ancient systems become dominant, exerting their prominent role in maintaining postural stability. The hemiplegic patient no longer has the flexibility to generate an action based on internal goals and desires.
APRAXIA Many cortical lesions result in coordination deficits that cannot be attributed to hemiplegia, motoric weakness, sensory loss or motivation. While the term apraxia means no action, it is used in a more general sense to describe a loss of motor skill. Ideomotor apraxia: the patient appears to have a rough idea of what the desired action is, but has problem in executing the action properly. Ideational apraxia: the patient knowledge about the intent of an action is disrupted. She/he may no longer comprehend the appropriate use of a tool. The left parietal lobe may contain the representation of skilled movements, perhaps reflecting the fact that skilled movements involve dynamic transformation in space. When representations are damaged, the patient has difficulty generating these actions or recognizing them when produced by others. The implementation of action, however, requires that the representations be transformed into specific motor plans. This involves additional processing by premotor and prefrontal areas involved in motor control. Damage to these areas also can produce apraxia, but will not disrupt the ability to perceive such actions when produced by another individual.
Clinical cases. DF, a 35 year old woman following a bilateral lesion of occipitotemporal cortex (ventral route), was unable to recognize objects. She was also unable to demonstrate with her fingers the size of visually inspected objects. By contrast, when instructed to take objects by performing prehension movements, she was quite accurate, and her maximum grip size correlated normally with object size (Goodale et al., 1991).
The second case is that of AT, also a 35 year old woman, with a lesion of the occipitotemporal region that was likely to have interrupted the dorsal route of visual processing. AT was able to recognize objects, and was also able to demonstrate their size with their fingers. By contrast, preshape of the hand during object-directed movements was incorrect. Correlation between object size and maximum grip size was lacking, with the consequence that objects could not be grasped between the fingertips; instead the patient made akward palmar grasps. Interstingly, while AT could not preshape her hand for neutral objects like plastic cylinders, yet when faced with a familiar object whose size is a semantic property, like a lip stick, she could grasp it with reasonable accuracy (Jeannerod at al., 1994).
Based upon such data, Goodale and Milner (1992) refined the Mishkin-Ungerleider description of visual system. Though still accepting that the ventral system plays a major role in the perceptual identification of objects, they suggest that the dorsal system mediates the required sensorimotor transformations for visually guided actions directed at such objects. They replace the ‘where’ system with the ‘how’ system.