Efferent Connections of the Cerebellar Hemispheres
The cerebellar hemispheres are linked functionally to the cerebral cortex, which provides inputs to the hemispheres via the deep pontine nuclei or, more indirectly, through the red nucleus and inferior olivary nucleus. The Purkinje cell outputs from the intermediate zone of the hemisphere are directed onto the interposed nuclei, while the Purkinje cell axons of more lateral regions of the hemisphere project to the dentate nucleus (Fig. 21-12). The interposed nuclei project through the superior cerebellar peduncle to the contralateral red nucleus and, thus, complete a feedback circuit between the red nucleus and cerebellar cortex (Figs. 21-14 and 21-15). This feedback circuit can be summarized as follows: red nucleus ^ inferior olivary nucleus (crossed fibers that enter the inferior cerebellar peduncle) ^ contralateral intermediate zone of anterior and posterior lobes of cerebellar cortex ^ interposed nuclei ^ (superior cerebellar peduncle) ^ contralateral red nucleus ^ to excite flexor motor neurons of the side of spinal cord contralateral to the red nucleus (because the rubrospinal tract is crossed).
This feedback circuit to the red nucleus thus enables the intermediate zone of the cerebellar cortex to control neuronal activity within the red nucleus and, ultimately, of the flexor motor neurons of the cervical spinal cord. In effect, by controlling flexor motor neurons, it provides the cerebellar hemispheres with an additional mechanism by which it can control coordination and execution of movements associated mainly with muscles of the arm.
FIGURE 21-15 The overall feedback pathway between the red nucleus and cerebellum. The red nucleus projects to the cerebellum via a synapse in the inferior olivary nucleus (rubro-olivary projections shown in green and olivocerebellar fibers shown in blue). The cerebellum, in turn, projects back to the red nucleus from the interposed nucleus (shown in red, which includes a Purkinje cell axonal input to interposed nuclei). The relationship of this circuit with the spinal cord is indicated by the presence of the rubrospinal tract.
The most powerful means by which the cerebellar hemispheres can affect the planning, initiation, and coordination of motor responses is with its relationships with the cerebral cortex. As indicated previously, the primary region of cerebellum involved in these functions is the cerebellar hemisphere. It receives massive numbers of fibers from the cerebral cortex that are topographically relayed from the deep pontine nuclei via the middle cere-bellar peduncle. In turn, the outflow from the cerebellar hemisphere is directed on the dentate nucleus. Fibers arising from the dentate nucleus enter the superior cerebellar peduncle and project beyond the red nucleus to the ventrolateral nucleus (VL) of the thalamus. Neurons arising from the VL project to the motor cortex (Fig. 21-16). This circuit thus comprises a feedback network linking the cerebral and cerebellar cortices and is summarized as follows: cerebral cortex ^ deep pontine nuclei (middle cerebellar peduncle crossed to) ^ contralateral cerebellar hemispheres of the anterior and posterior lobes ^ dentate nucleus ^ (superior cerebellar peduncle crossed to) ^ contralateral ventrolateral thalamic nucleus ^ motor cortex (on side opposite the cerebellar hemisphere, which receives the cerebral cortical inputs and which gives rise to feedback pathway) (corticospinal tract) ^ contralat-eral spinal cord.
In this manner, feedback signals from the cerebellar cortex can assist in the planning, coordination, and execution of motor responses initiated from the cerebral cortex.
FIGURE 21-16 The overall feedback pathway between the cerebral cortex and cerebellar cortex. The cerebral cortex projects to the cerebellum via a synapse in the basilar pons (shown in blue) second-order neurons pass through the middle cerebellar peduncle as pontocerebellar fibers to the cerebellar cortex (shown in blue). The feedback to the cerebral cortex involves a projection from the dentate nucleus to the ventrolateral nucleus of the thalamus, which, in turn, projects to the motor and premotor cortices (both shown in red).
FIGURE 21-17 Feedback pathways. Diagram illustrates the overall inputs to the spinal cord from the brainstem and cerebral cortex. These inputs to the spinal cord are sculpted by the actions of the cerebellum via feedback pathways to key brainstem nuclei and the cerebral cortex. Brainstem structures, which regulate spinal cord motor neurons and receive important feedback from the cerebellum, include the red nucleus, reticular formation, and vestibular nucleus. Likewise, the actions of the corticospinal tract on motor functions of the spinal cord are also powerfully regulated by the cerebellum. Reciprocal "feedback" relationships linking reticular formation and vestibular nuclei with the cerebellum and spinal cord are shown in blue; those linking the red nucleus, cerebellum, and spinal cord are shown in red; and those linking the cerebral cortex, deep pontine nuclei, cerebellum, and spinal cord are shown in green.
Evidence that cerebellar neurons function in this manner was provided from experiments in which single unit recordings were taken from monkey motor and cerebellar cortices prior to and during motor activity. It was shown that cerebellar cortex neuronal discharges, as well as those discharges recorded from the motor cortex, preceded the movement. Experiments of this sort have clearly suggested that cerebellar cortical neurons likely help to organize and plan responses normally associated with the motor regions of the cerebral cortex.
When viewed as a whole, we can now see how the cerebellum powerfully regulates the activity of motor neurons of the spinal cord through each of these feedback circuits (Fig. 21-17). Postural mechanisms, balance, and muscle tone are regulated by the outputs of the fastigial nucleus to the vestibular nuclei and reticular formation, whose axons innervate primarily extensor motor neurons. The outputs of the interposed and dentate nuclei to the red nucleus and motor regions of the cerebral cortex (via the ventrolateral thalamic nucleus), respectively, can influence the distal musculature innervated by motor neurons of the spinal cord, which receive inputs from the red nucleus and motor cortex.
Motor Learning and The Cerebellum
Experimental evidence has suggested that the cerebellum is involved in motor learning. By this, it is meant that long-lasting changes in synaptic efficacy and modifications in synaptic connections take place after a response has taken place. Such changes can occur in any one of the synaptic connections that exist within the cerebellar cortex. However, it is more likely that the primary regions involved in motor learning include the mossy and climbing fiber connections that are made with the Purkinje cell. As indicated earlier, the Purkinje cell response to parallel fiber inputs is greatly modified following stimulation of climbing fibers. Therefore, it is reasonable to assume that repetition of a given response may quite easily lead to changes in synaptic plasticity involving Purkinje cells. Such changes would also likely produce changes in the patterns of coded neural signals that are fed back to distal structures such as the cerebral cortex. The changes in the neural response pattern in the Purkinje cell as a function of movement would constitute a learned cerebellar response. The likelihood that learning takes place in the cerebellum is enhanced by the knowledge that the cerebel-lar cortex receives such a wide variety of sensory inputs, which include somatosensory, vestibular, visual, and auditory impulses. It is plausible to speculate that each of these sensory modalities may contribute to the learning process within the cerebellum.
There is much that we do not know about the role of learning in the cerebellum. We have little knowledge about the regions of cerebellum where learning takes place. We also have little understanding of the specific mechanisms involved in learning and what role specific sensory inputs play in the learning process. It is anticipated that future research will help to provide us with a better understanding of these mechanisms.
Cerebellar Disorders
In our attempts to develop an understanding of the nature of cerebellar disorders, it is useful to recognize two features of cerebellar anatomy and physiology. One such feature is the nature of the feedback pathways between the cerebellum and other regions of the CNS associated with motor functions. A second feature is the anatomical and functional aspects of the medial-to-lateral organization of the cerebellar cortex with respect to their relationships with deep cerebellar nuclei and their projection targets beyond the cerebellum.
Consider first the feedback pathways of the cerebellum. When one or more of the feedback mechanisms are disrupted, a disorder of movement on the side of the body ipsilateral to the lesion emerges. The two types of such cer-ebellar disorders that have been described include ataxia (i.e., errors in the range, rate, force, and direction of movement resulting in loss of muscle coordination in producing smooth movements) and hypotonia (i.e., diminution of muscle tone).
Ataxia
There are a number of disorders that include ataxic movements. In particular, loss of coordination (called asynergy) is quite common in patients who have incurred cerebellar lesions. The components of complex movements occur as a series of simple individual movements (called decomposition of movement). The patient may also not be able to accurately move his or her hand in space. For example, if the patient is asked to move his or hand hand to touch his or her nose, he or she will either undershoot or overshoot the mark. This disorder is called dysmetria. Similarly, another disorder, called "past pointing," refers to the con-diction in which the patient is asked to reach a point with his finger but overshoots it. Alternatively, the patient may be unable to make rapid alternating rotational movements of his or her hand. This disorder is called dysdiadochoki-nesia. As the patient voluntarily attempts to move his or her limb, he or she may display a tremor, which is called an intention tremor. All of these disorders most frequently involve the cerebellar hemispheres and presumably reflect a disruption of the feedback circuit between the cerebellar cortex and the cerebral cortex that governs movements of the distal musculature.
Ataxia may also result from damage to other regions of the cerebellum. If the lesion involves the flocculonodular lobe or the vermal region of the posterior or anterior lobes, patients will display gait ataxia. They will walk with a very wide and slow gait (i.e., with legs widely separated), and they may also have a tendency to fall toward the side of the lesion. These symptoms have been shown to occur in cases of alcoholic cerebellar degeneration preferentially affecting the anterior lobe. Such lesions interfere with the feedback circuits involving either (or both) the vestibulocerebellum or spinocerebellum and their connections with the fastigial nucleus and its output pathways to the vestibular nuclei, reticular formation, and, ultimately, the spinal cord.
Hypotonia
Hypotonia has been associated with damage to parts of the cerebellar cortex, but the specific regions have not been clearly identified. It has been suggested that lesions, possibly of the paravermal region or hemisphere of the posterior lobe, are linked to this disorder. The precise mechanism underlying this disorder remains unknown. Because the outputs of the cerebellum to a brainstem structure, such as the lateral vestibular nucleus (which excites extensor motor neurons), are typically excitatory, such a lesion may cause loss of excitation to the lateral vestibular nucleus (from the fastigial nucleus), resulting in loss of excitatory input to the spinal cord motor neurons and subsequent hypotonia.
Cerebellar Nystagmus and Gait Ataxia
Lesions of the vermal region of the cerebellar cortex or fastigial nucleus can result in cerebellar nystagmus. Presumably, the effect is due to a disruption of the inputs to the medial longitudinal fasciculus from vestibular nuclei. This is likely caused by the loss of or change in inputs to the vestibular nuclei from the fastigial nucleus because of the lesion in the fastigial nucleus or cerebellar cortical regions that project to the fastigial nucleus.
The medial-to-lateral organization of the cerebellar cortex also provides a very useful means for our understanding of disorders of the cerebellum. In this context, we can simply compare disorders of the midline region against those associated with the hemispheres.
Syndromes Associated With the Midline Region of the Cerebellar Cortex
As noted above, a lesion or tumor, such as a medulloblas-toma, of the vermal region will result in nystagmus and an unsteady gait. This syndrome can be understood in terms of the projection target of the midline (vermal) region, namely, the fastigial nucleus and its targets, the vestibular nuclei and reticular formation, whose inputs are disrupted by the cerebellar lesion.
Syndromes Associated With the Cerebellar Hemispheres
The syndromes associated with a lesion of the cerebellar hemisphere are described above and include asynergia, decomposition of movement, intention tremor, and dys-diadochokinesia. The key point here is that cerebellar hemispheres project mainly to the dentate nucleus, which, in turn, sends signals to the motor cortex via the VL of thalamus. A lesion of the hemisphere will disrupt feedback to the motor cortex, which then results in the syndromes associated with intentional movements.
Clinical Case
History
William is a 59-year-old man who has been drinking alcohol heavily since the age of 15. Sometimes, he would consume up to 2 pints of whiskey per day, although he would often drink cheap wine, cold syrup, or anything with alcohol in it that he could find in large amounts. He finally decided to seek medical attention when he began to have problems with an unsteady,"waddling"gait. He now needed to stand with his feet far apart in order to maintain his balance.
Examination
The physician who evaluated William tested his cognitive abilities and found some minor memory deficits. When asked to touch the doctor’s finger,followed by touching his own nose, William’s hand movements were somewhat unsteady and missed the target, which he then corrected. When asked to slide one heel down the contralateral shin, William’s movements were clumsy and far worse than they were with the arms. When asked to walk, his walk was slightly unsteady, with his feet placed wide apart. When attempting to walk in tandem fashion, with one foot in front of the other, he began to fall. The neurologist ordered a magnetic resonance imaging (MRI) scan of William’s head.
Explanation
William has alcoholic cerebellar degeneration. It is most likely caused by degeneration of neurons of the cerebellar cortex via nutritional deficiency. The cells of the cerebellum most affected are the Purkinje neurons, usually in the regions of the anterior aspects of the vermal and paravermal portions of the anterior lobe (see Fig. 21-7). Because of involvement of the midline of the cerebellum, structures such as the trunk are primarily affected, causing gait difficulties. Because the legs are represented in the anterior aspect of the paravermal portion of the anterior lobe in the cerebellar homunculus,the legs are affected more than the arms.The gait deficit described in William’s legs is referred to as ataxia.
Imaging scans, such as an MRI scan, are able to demonstrate loss of volume in the vermis. This loss of volume is often indicative of a chronic, rather than an acute, problem and is irreversible. Therapies commonly used to minimize any further damage include vitamin replacement (i.e„ nicotinic acid therapy plus other vitamins),discontinuation of alcohol,and physical therapy.
SUMMARY TABLE
Functions and Dysfunctions of Input-Output Relationships of the Cerebellum
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Afferent Connections of the Cerebellum |
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Structure |
Origin |
Function |
Cerebellar Target |
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From Spinal Cord |
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Dorsal spinocerebellar tract |
Nucleus dorsalis of Clarke |
Transmits signals from muscle spindles (status of individual muscles) and Golgi tendon organs (status of whole limb) from lower limbs to ipsilateral cerebellum |
Anterior lobe |
|
Ventral spinocerebellar tract |
Ventral horn of spinal gray matter |
Transmits signals from Golgi tendon organs conveying information concerning whole limb movement and postural adjustments from lower limb mainly to ipsilateral cerebellum |
Anterior lobe |
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Cuneocerebellar tract |
Accessory cuneate nucleus |
Conveys signals from muscle spindles of upper limbs to ipsilateral cerebellum |
Anterior lobe and parts of posterior lobe |
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Rostral spinocerebellar tract |
Gray matter of cervical spinal cord |
Conveys signals concerning whole limb movement from upper limb to cerebellum in animals (pathway in humans has not been identified) |
Anterior lobe |
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From Brainstem |
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Olivocerebellar tract |
Inferior olivary nucleus |
Transmits signals from red nucleus and spinal cord (cutaneous, joint, and muscle spindle afferents) reflecting the status of the inferior olivary nucleus to these inputs to contralateral cerebellum |
Topographically arranged projections to anterior and posterior lobes |
|
Vestibulocerebellar fibers |
Vestibular apparatus and medial and inferior vestibular nucleus |
Transmission of signals from otolith organ and semicircular canals indicating the status of vestibular neurons and the position of the head in space to cerebellum |
Flocculonodular lobe |
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Reticulocerebel-lar fibers |
Lateral and paramedian nucleus (medulla) and reticulotegmen-tal nucleus (pons) |
Receives inputs from cerebral cortex and lateral reticular nucleus receives tactile impulses; the outputs of these reticular neurons to cerebellum reflect these inputs as well as the activity of reticulospinal neurons |
Anterior and posterior lobes of cerebellum |
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From Cerebral Cortex |
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Rubrocerebellar fibers |
Red nucleus |
Receives inputs from cerebral cortex and transmits the status of red nucleus neuronal activity via an interneuron in inferior olivary nucleus to contralateral cerebellum |
Topographically arranged projections to anterior and posterior lobes |
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Pontocerebellar fibers |
Deep pontine nuclei |
Receives direct inputs from wide regions of cerebral cortex and transmits these signals to contralateral cerebellum |
Somatotopic (and topographic) distribution to anterior and posterior lobes of cerebellum |
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Structure |
Origin |
Function |
Cerebellar Target |
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Other Inputs |
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Monoaminergic pathways |
Raphe nuclei and locus ceruleus |
Projections to cerebellum modulates activities of these neurons |
Wide areas of cerebellar cortex, including deep cerebellar nuclei |
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Tectocerebellar fibers |
Superior and inferior colliculi |
Transmits visual and auditory signals via deep pontine nuclei |
Anterior and posterior lobes of cerebellum |
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Trigeminocere-bellar fibers |
Mesencephalic trigeminal nucleus |
Conveys secondary proprioceptive signals from muscle spindles of face and jaw to cerebellum |
Mainly vermal and par-avermal regions of cerebellar cortex |
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|
Efferent Connections of the Cerebellum |
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|
Origin |
Pathway |
Function |
Associated Disorder |
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Fastigial nucleus |
Projects to reticular formation and vestibular nuclei |
Feedback pathway between cerebellum and reticular formation and vestibular system for regulation of posture, muscle tone, and eye movements |
Wide ataxic gait; nystagmus; patient may fall toward side of lesion |
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|
Interposed nuclei |
Projects to contralateral red nucleus via superior cerebellar peduncle |
Feedback pathway between red nucleus and cerebellum; regulates motor functions of red nucleus |
Dysfunctions associated with selective lesions of red nucleus and their relationships with cerebellum have not been clearly identified; several possibilities include intention tremor and hypotonia |
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|
Dentate nucleus |
Projects to contralateral motor cortex via superior cerebellar peduncle and synapses in ventrolateral nucleus of thalamus |
Feedback pathway between cerebral and cerebellar cortices; regulates and coordinates voluntary movements associated with the cerebral cortex |
Loss of coordination (asynergy); decomposition of movement; dys-metria; dysdiadochokinesia; intention tremor |
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