Chapter 13: The Cerebellum

The cerebellum is a fascinating brain structure; more so than many because several of its properties and organizational principles are unexpected. It is a little brain unto itself; roughly half of the neurons in the central nervous system are located in the cerebellum, and when stretched out, it is more than several square meters. That so much of the central nervous system is devoted to the cerebellum means that its functions are particularly important or complex, requiring so much neural power; indeed, it is likely both. It is no surprise that early anatomists termed this structure the cerebellum, which means little brain in Latin. Its microscopic structure is nearly crystalline in its organization, providing insight into a similarity in the way it processes information across this large brain region.

We know that the cerebellum plays a key role in movement, and it does so by regulating the functions of the motor pathways (see Figure 10–2). When this major brain structure is damaged, movements that were smooth and steered accurately become uncoordinated and erratic. Important insights into the general role of the cerebellum in motor control can be gained by considering that the cerebellum receives information from most of the sensory systems and from virtually all other components of the limb and eye movement systems. With these connections, the cerebellum is poised to compare information about the intention of an upcoming movement, by receiving information from the motor pathways, with what actually occurs, by retrieving information from the sensory systems. Research has shown that the cerebellum may compute control signals to correct for differences between intent and action, or errors. The cerebellum, in turn, provides a major input to the brain stem and cortical pathways for limb, trunk, and eye movement control.

The cerebellum also receives information from areas of the central nervous system that do not play a direct role in movement control, such as the parietal association cortex and the limbic association cortex. How is this finding reconciled with its important role in movement control? Many areas of association cortex, as well as higher-order sensory areas, help in the planning of movements—for example, by allowing an individual's motivation state of being thirsty to influence when to reach for a glass of water or by allowing the determination of the location of the glass to ensure reaching accuracy. However, the cerebellum serves nonmotor functions, too. Indeed, cerebellar damage can produce impairments in language, decision making, and affect that cannot be attributed to motor defects. Contributing to the surprise of the cerebellum, it is involved in many diverse functions, like the central nervous system itself.

Because the three-dimensional organization of the cerebellum is so complex (Figure 13–2), rivaling that of the cerebral hemispheres and diencephalon, its gross anatomy is considered before its functional organization. Located dorsal to the pons and medulla (Figure 13–2A, B), the cerebellum is separated from the overlying cerebral cortex by a tough flap in the dura, the cerebellar tentorium (Figure 13–3B; see Figure 3–15). The inferior surface of the cerebellum is incompletely divided by the posterior cerebellar incisure (Figure 13–2C). The cerebellum comprises an outer cortex containing neuronal cell bodies overlying a region that contains predominantly myelinated axons. The cerebellar cortex contains an extraordinary number of neurons and a rich array of neuron types (see below).

Two shallow grooves running from rostral to caudal divide the cerebellar cortex into the vermis, located along the midline, and two hemispheres (Figure 13–2). This anatomical distinction marks the specific functional divisions of the cerebellar cortex (see below). Like the cerebral cortex, the cerebellar cortex is highly convoluted. These characteristic folds, termed folia, are equivalent to the gyri of the cerebral cortex. They vastly increase the amount of cerebellar cortex that can be packed into the posterior cranial fossa (see Figure 3–15).

The cerebellar cortex is organized into groups of folia, termed lobules, that are separated from one another by fissures. In a sagittal section through the vermis, the lobules appear to radiate from the apex of the roof of the fourth ventricle (Figure 13–3A, inset). Anatomists recognize 10 lobules, whose nomenclature is used largely by specialists studying the cerebellum. Two fissures are particularly deep and divide the various lobules into three lobes (Figures 13–2 and 13–3A). The primary fissure separates the anterior lobe from the posterior lobe. The flocculonodular lobe is separated from the posterior lobe by the posterolateral fissure. This lobe consists of the nodulus, located on the midline (equivalent to the vermis of the flocculonodular lobe), and the two flocculi, on either side. The anterior lobe is important in the control of limb and trunk movements, whereas the posterior lobe may be somewhat more important in movement planning and in the nonmotor functions of the cerebellum. The flocculonodular lobe plays a key role in maintaining balance and controlling eye movement.

Beneath the cerebellar cortex is the white matter, which contains axons coursing to and from the cortex (Figure 13–3). The branching pattern of the white matter of the cerebellum inspired early anatomists to refer to it as the arbor vitae (Latin for "tree of life"); hence, the name folia (Latin for "leaves") rather than gyri, used to describe cerebral cortex convolutions. Embedded within the cerebellar white matter are four bilaterally paired nuclei, the deep cerebellar nuclei: the fastigial nucleus, the globose nucleus, the emboliform nucleus, and the dentate nucleus. The globose and emboliform nuclei are collectively termed the interposed nuclei. These nuclei are shown on the cerebellar cortex surface (Figure 13–2A), as if it were transparent; they are also shown in the schematic transverse section through the pons and cerebellum (Figure 13–4). It is tempting to think that the functional relation between the deep nuclei and cortex of the cerebellum is similar to that of the thalamus and cerebral cortex. But that is wrong; we will see that neurons in the cerebellar cortex send connections to the deep nuclei, not the reverse as with the thalamus and cerebral cortex.

Axons projecting to and from the cerebellum course through the peduncles (Figure 13–2B, C): The superior cerebellar peduncle contains mostly efferent axons, the middle cerebellar peduncle contains only afferent axons, and the inferior cerebellar peduncle contains both afferent and efferent axons. An alternate nomenclature is often used for the cerebellar peduncles in the clinical and scientific literature. The superior cerebellar peduncle is also called the brachium conjunctivum; the middle cerebellar peduncle, the brachium pontis; and the inferior cerebellar peduncle, the restiform body. The various peduncles are distinguished in Figure 13–2B, C because each one has been given a different cut surface in the drawing. Three distinct peduncles would not be apparent had a single cut been drawn.

The Cerebellum Has a Basic Circuit

Figure 13–4 shows the circuits of the cerebellum. There are two major sets of inputs to the cerebellum—termed climbing and mossy fibers—and, with some exceptions, both sets of inputs are directed to neurons in the deep nuclei and cortex. Climbing fibers originate from a single nucleus, the inferior olivary nucleus (see Figure 13–11B); mossy fibers originate from many different brain stem and spinal cord nuclei. In the cortex, climbing fibers synapse on Purkinje neurons, which generate a cerebellar cortex output signal by projecting to neurons in the deep nuclei. Interestingly, many neurons of the vestibular nuclei have similar connections as the deep cerebellar nuclei, receiving inputs from climbing fibers and Purkinje neurons (see below). This points to common developmental origins of the two sets of nuclei.

Mossy fibers engage a network of cerebellar excitatory and inhibitory interneurons (Figure 13–4A). The excitatory interneurons, in turn, synapse on Purkinje neurons, also leading to a cerebellar cortex output signal. The inhibitory interneurons help to regulate Purkinje neurons activity, making it easier—with less inhibition—or harder with more, for the climbing and mossy fibers to generate a cortical output signal. Surprisingly, the Purkinje neuron is an inhibitory projection neuron.

All Three Functional Divisions of the Cerebellum Display a Similar Input-Output Organization

The cerebellum has three functional divisions, each consisting of a portion of the cerebellar cortex and one or more deep nuclei (Figures 13–2 and 13–5). Each functional division of the cerebellum uses the same basic circuit to carry out its own tasks, the circuit shown in Figure 13–4A. However, each functional division differs from the others with respect to the specific input sources and the specific structures to which it projects. The divisions are named for their major sources of information:

• The spinocerebellum, which receives highly organized somatic sensory inputs from the spinal cord, is important in controlling the posture and movements of the trunk and limbs (Figure 13–5A). The spinocerebellum comprises the vermis; the adjoining intermediate hemisphere, of both the anterior and posterior lobes; and the fastigial and interposed nuclei. This division also receives information from structures other than the spinal cord; a portion receives trigeminal and other sensory cranial nerve information. A portion of the vermis of the posterior lobe may play a role in nonmotor functions.

• The cerebrocerebellum, which receives input indirectly from the cerebral cortex, participates in the planning of movement and nonmotor functions. This division consists of the lateral hemisphere, in both the anterior and posterior lobes, and the dentate nucleus.

• The vestibulocerebellum, which receives input directly from the vestibular labyrinth as well as the vestibular nuclei, helps in maintaining balance and controlling head and eye movements. This cerebellar division corresponds to the flocculonodular lobe. There is no deep cerebellar nucleus for the vestibulocerebellum. Instead, the vestibular nuclei serve a similar role.

The spinocerebellum projects to the lateral and medial motor systems

The spinocerebellum is important in the control of body musculature. It is somatotopically organized: The vermis controls axial and proximal muscles and the intermediate hemisphere, limb muscles (Figure 13–5A). This mediolateral somatotopic arrangement recalls the somatotopic organization of the ventral horn, where medial motor neurons innervate axial and proximal limb muscles, and those located laterally innervate more distal muscles (see Figure 10–3). As with the descending motor pathways, the components of the spinocerebellum that control the distal limb are predominantly crossed, whereas the components controlling proximal and axial muscles have a more bilateral organization.

The organization of the spinocerebellum that captures both its salient and clinical features (see later section on the motor effects of cerebellar damage) is shown in Figure 13–6. It receives somatic sensory information primarily from mechanoreceptors, especially those that innervate muscle (see Table 4–1), from the limbs and trunk, via ipsilateral spinocerebellar tracts. The dorsal spinocerebellar tract originates from Clarke's nucleus and transmits sensory information from the leg and lower trunk to the cerebellar nuclei and cortex. By contrast, the cuneocerebellar tract originates from the accessory cuneate nucleus. It transmits sensory information from the arm and upper trunk. Several cerebellar conditions, including Fredrich ataxia, produce limb and trunk control impairments by causing degeneration in these ascending cerebellar pathways (see clinical case in this chapter). Ataxia is a kind of incoordination that occurs following many different kinds of cerebellar disease.

The axons of both of these tracts travel through the inferior cerebellar peduncle (Figure 13–6); they are examples of mossy fibers, forming connections with diverse cerebellar neurons. For limb control, the spinocerebellar axons synapse on neurons in the interposed nuclei. Information also projects to neurons of the intermediate hemisphere of the cerebellar cortex, where Purkinje neurons project to the interposed nuclei (Figure 13–5B). The interposed nuclei project from the cerebellum, through the superior cerebellar peduncle, to the magnocellular component of the red nucleus and, predominantly, via the ventrolateral nucleus of the thalamus, to motor areas of the frontal lobe (Figures 13–3B). These components of the motor systems give rise to the lateral descending pathways: the rubrospinal and lateral corticospinal tracts. The logic of the laterality of these connections ensures that somatic sensory information from one limb is projected to the side of the spinocerebellum that, in turns, projects to the parts of the lateral motor pathways that control the same limb.

For proximal muscle control, including the trunk and upper back, the circuitry is more bilaterally organized (Figures 13–5B and 13–7). Here the dorsal spinocerebellar and cuneocerebellar tracts project both to the fastigial nuclei and the vermis of the cerebellar cortex, which, in turn, also projects to the fastigial nuclei (Figure 13–7). This deep nucleus influences motor neurons primarily through their projections onto the medial descending pathways, the reticulospinal (Figure 13–7) and vestibulospinal tracts (Figure 12–3B). The fastigial nucleus has also a small ascending projection, via a thalamic relay, to cells of origin of the ventral corticospinal tract in primary and premotor cortical areas. This efferent projection exits through the superior cerebellar peduncle. Some Purkinje neurons of the vermis send their axons to the vestibular nuclei (see following section on vestibulocerebellum).

Two other spinocerebellar pathways (Figure 13–6B,)—the ventral and rostral spinocerebellar tracts, for the lower and upper halves of the body—are thought to transmit internal feedback signals for correcting inaccurate movements rather than somatic sensory information. Many of the axons that decussate in the spinal cord cross again in the superior cerebellar peduncle to terminate in the ipsilateral cerebellum; these axons are "doubly crossed." There are also trigeminocerebellar pathways that originate from the spinal trigeminal nucleus, principally from parts of the interpolar and oral nuclei (see Chapter 6).

The cerebrocerebellum projects to premotor and association cortical areas

The cerebrocerebellum (Figures 13–5B and 13–8) is primarily involved in the planning of movement and is interconnected with diverse regions of the cerebral cortex. The major input to the cerebrocerebellum is from the contralateral cerebral cortex, not only from the motor areas but also from the sensory and association areas (Figure 13–8). This projection is relayed by neurons in the ipsilateral pontine nuclei (Figure 13–8A, and inset). The pontine nuclei, in turn, project to the contralateral cerebellar cortex through the middle cerebellar peduncle. Purkinje neurons of the cerebrocerebellum project to the dentate nucleus, the largest and most lateral of the deep nuclei. Neurons in the dentate nucleus project their axons to two main motor control centers. The first is the motor relay nucleus of the thalamus, the ventrolateral nucleus, and from here, to the primary motor cortex and premotor areas. The logic of the laterality of these connections is that the cerebral cortex controlling one limb also projects to the cerebrocerebellum controlling the same limb.

The second motor control center to which the dentate nucleus projects is the red nucleus; however, it projects to the parvocellular division, not to the magnocellular division. Whereas the magnocellular portion of the red nucleus gives rise to the rubrospinal tract (see Chapter 10), the parvocellular division projects to the ipsilateral inferior olivary nucleus, the source of climbing fiber input to the cerebellum (see below). The parvocellular red nucleus forms a loop: first connecting to the ipsilateral olive, from there to the contralateral dentate, and then back to the same parvocellular red nucleus via a decussation in the superior cerebellar peduncle. Whereas the function of this loop is not known, damage along the loop can produce tremor.

Recent functional imaging and clinical studies in humans suggest that the most ventrolateral and posterior portion of the dentate nucleus participates in nonmotor functions, including cognition and language. There may be a distinctive anatomical correlate for the role of the dentate nucleus in higher brain functions. In the monkey, where anatomical tracer studies can be conducted, a portion of the dentate nucleus is analogous to the ventrolateral dentate in the human. Different sets of neurons in this portion of the monkey's dentate nucleus project—via integrative thalamic nuclei, including the medial dorsal nucleus—to the association cortex: to prefrontal association cortex, involved in working memory, where information that is used to plan and shape upcoming behaviors is temporarily stored; and to posterior parietal association cortex, the interface of visual perception, attention, and motor action. Thus, the cerebrocerebellum has the connections to mediate several higher brain functions.

The vestibulocerebellum projects to brain stem centers for controlling eye and head movements

The vestibulocerebellum is crucial for controlling gaze, through the combined control of eye and head movements (Figures 13–5B and 13–9). This cerebellar division receives information from primary vestibular afferents and secondary vestibular neurons in the vestibular nuclei. In fact, the vestibular afferents are the only primary sensory neurons that project directly to the cerebellum. The cortical component of the vestibulocerebellum projects to the vestibular nuclei: the lateral, medial, inferior, and superior vestibular nuclei (Figure 13–9). As we saw in Chapter 12, the vestibular nuclei are important for smooth pursuit eye movements as well as the vestibuloocular reflexes. The vestubulocerebellum participates in coordinating neck muscle function with eye control, via the medial vestibulospinal tract; maintaining balance, via the lateral vestibulospinal tract; and maintaining eye movement control, via fibers in the medial longitudinal fasciculus to extraocular motor nuclei.

Damage to the Cerebellum Produces Limb Motor Signs on the Same Side as the Lesion

There are three classic signs of cerebellar damage: ataxia, tremor, and nystagmus. Ataxia is inaccuracy in the speed, force, and distance of movement. In reaching for an object, a patient with cerebellar damage overshoots (hypermetria) or undershoots (hypometria) the target. Ataxia of gait produces staggering and lurching. Ataxia is due to impairments in interjoint coordination. Tremor is involuntary oscillation of the limbs or trunk. Cerebellar tremor is characteristically present when the patient is trying to perform a movement requiring skill, such as touching the examiner's finger or bringing a forkful of food to the mouth. Nystagmus is a rhythmic involuntary oscillation of the eyes. Ataxia and nystagmus typically occur after damage to cerebellar inputs, such as the spinocerebellar tracts or the inferior cerebellar peduncle. In contrast, tremor is more often a consequence of damage to the cerebellar output pathways, such as the superior cerebellar peduncle. However, combinations of signs typically occur with damage to the cerebellum depending on the site and size of the lesion.

Knowledge of the anatomy of the descending projection pathways is crucial for understanding why unilateral cerebellar damage typically produces ipsilateral limb motor signs. Ipsilateral signs occur because both the cerebellar efferent projections and the descending pathways (ie, the targets of cerebellar action) are crossed. The combined decussations result in a system of connections that is "doubly crossed" (Figure 13–10). Damage to cerebellar input from the spinal cord also produces ipsilateral signs because the principal spinocerebellar pathways, the dorsal spinocerebellar and cuneocerebellar tracts, ascend ipsilaterally. Thus, whether damage occurs to cerebellar inputs or outputs, or to the cerebellum itself, neurological signs are present on the ipsilateral side.

Occlusion of the posterior inferior cerebellar artery (PICA) infarcts the inferior cerebellar peduncle as well as most of the deep cerebellar nuclei. Two key signs related to this infarction are nystagmus (also a consequence of damage to the vestibular nuclei) and ipsilateral limb ataxia. These are the key cerebellar signs associated with the lateral medullary, or Wallenberg, syndrome (see Clinical Cases for Chapters 6 and 15). Somatic sensory deficits are also present with PICA occlusion because infarction of the dorsolateral medulla interrupts ascending fibers of the anterolateral system (see Chapter 5) as well as the trigeminal spinal tract and nucleus (see Chapter 6). Importantly, even though the cerebellum receives sensory information, especially somatic sensory information, patients do not have loss of sensation; for example, they do not report sensory threshold changes, numbness, or visual blind spots.

Although the principal signs of cerebellar damage are motor, patients with cerebellar damage may also have behavioral impairments that cannot be attributed to a primary motor impairment. This phenomenon has been described as the cerebellar "cognitive affective syndrome." The syndrome is characterized by impairments in executive functions (eg, planning behaviors), abstract reasoning, visuospatial reasoning, and working memory. Some patients have personality changes, with a blunting of affect. This syndrome is more prominent in patients with lesions of posterior lobe hemisphere (cognitive and language impairments) and posterior lobe vermis (defective affect). These changes could be due to impairments in processing information from diverse cortical regions—such as association areas, including limbic association cortex—carried by the corticopontine projection. It could also be related to damaging cerebellar regions that project to the dorsolateral prefrontal and other association areas. Interestingly, there are cerebellar structural changes in patients with autism spectrum disorder, a condition presenting with deficits in social interaction, impaired verbal and nonverbal communication, and expression of stereotyped patterns of behavior. This is a common neuropsychiatric disorder affecting about 1 in 150 individuals. Further, many of the genes associated with autism spectrum disorder are expressed in the cerebellum. While controversial, there is a growing body of basic and clinical evidence asserting the cerebellum's role in nonmotor functions and neuropsychiatric disorders.

The rest of this chapter examines the regional anatomy of the connections and cellular organization of the cerebellum. Sections through key levels, from caudal to rostral, are used to illustrate the locations of spinocerebellar tracts, the histology of the cerebellar cortex, the deep nuclei, and the efferent projections to the brain stem and thalamus.

Spinal Cord and Medullary Sections Reveal Nuclei and Paths Transmitting Somatic Sensory Information to the Cerebellum

Clarke's nucleus and the accessory cuneate nucleus are the principal nuclei that relay somatic sensory information to the spinocerebellum. Clarke's nucleus is found in the medial portion of the intermediate zone of the spinal cord gray matter (lamina VII) (Figure 13–11). This nucleus forms a column with a limited rostrocaudal distribution (Figure 13–6). In the human, Clarke's nucleus spans the eighth cervical segment (C8) to approximately the second lumbar segment (L2) and relays somatic sensory information from the lower limb and lower trunk. Because the caudal boundary of the nucleus is rostral to the lumbosacral enlargement, afferent fibers from most of the lower extremity first enter and ascend in the gracile fascicle (Figure 13–6). Then they leave the white matter to terminate in Clarke's nucleus. The dorsal spinocerebellar tract originates from Clarke's nucleus. The tract ascends in the outermost portion of the ipsilateral lateral column (Figure 13–11C) and enters the cerebellum via the inferior cerebellar peduncle (Figure 13–11A, B). The other pathway from the lower limb, the ventral spinocerebellar tract, is lateral to the ascending fibers of the anterolateral system (Figure 13–11C). The ventral spinocerebellar tract originates from diverse neurons in the ventral horn. The ventral spinocerebellar tract is a crossed spinal pathway, entering the cerebellum via the superior cerebellar peduncle, where some of the axons re-cross (Figure 13–12).

The caudal medulla contains the accessory cuneate nucleus (Figure 13–11A, B), which is rostral to the cuneate nucleus, important for perception (see Chapter 4). (The accessory cuneate nucleus is also termed the external cuneate nucleus.) The accessory cuneate nucleus relays somatic sensory information from the upper trunk and upper limb to the cerebellum, not for perception but for controlling movements. To reach the accessory cuneate nucleus, afferent fibers from the upper trunk, arm, and back of the head first course rostrally within the cervical spinal cord in the cuneate fascicle of the dorsal column (Figure 13–11A). The entire course of the cuneocerebellar tract is within the inferior cerebellar peduncle.

The Inferior Olivary Nucleus Is the Only Source of Climbing Fibers

The inferior olivary nucleus (Figure 13–11B), from which all climbing fibers originate, is a collection of three subnuclei (see Figure AII–8) that have somewhat different connections. It forms an elevation on the ventral surface of the medulla termed the olive (Figure AI–6). The inferior olivary nucleus consists of a convoluted sheet of neurons surrounded by the axons of the central tegmental tract, which originated from the ipsilateral parvocellular division of the red nucleus (see below). Neurons in the inferior olivary nucleus are electrically coupled, resulting in a synchrony of action among local groups of olivary neurons. The principal division of the nucleus (Figure 13–11B) is the largest in humans. Interestingly, in animals this division is associated with the cerebrocerebellum.

Dorsal to the inferior olivary nucleus is the lateral reticular nucleus (Figure 13–11B), which gives rise to a mossy fiber projection to the cerebellum. The lateral reticular nucleus receives sensory information from mechanoreceptors of the limbs and trunk as well as information from the motor cortex, by branches of corticospinal tract axons. Like neurons of the ventral spinocerebellar tract, the lateral reticular nucleus is thought to participate in correcting for movement errors.

The Vestibulocerebellum Receives Input From Primary and Secondary Vestibular Neurons

Purkinje neurons of the flocculonodular lobe send their axons primarily to the vestibular nuclei (Figure 13–11A, B), rather than to the deep cerebellar nuclei, as do Purkinje neurons in other regions of the cerebellum. (Exceptions exist; some Purkinje neurons of the flocculonodular lobe synapse in the fastigial nucleus, and some within the anterior and posterior lobe vermis synapse in the vestibular nuclei.) The vestibular nuclei are the anatomical equivalent of the deep cerebellar nuclei of the vestibulocerebellum because they share two similarities in the sources of afferent input, both: receive a projection from the inferior olivary nucleus and are monosynaptically inhibited by Purkinje neurons.

The flocculonodular lobe projects to the medial, inferior, and superior vestibular nuclei. These nuclei—especially the medial vestibular nucleus—give rise to the medial vestibulospinal tract, for coordinating head and eye movements (Chapter 12). The fastigial nucleus projects primarily to the lateral vestibular nucleus, which gives rise to the lateral vestibulospinal tract, for controlling axial muscles to maintain balance and posture. The vestibular nuclei also contribute to the medial longitudinal fasciculus (Figures 13–11A, 13–12, and 13–15B), which plays a key role in eye muscle control through projections to the extraocular motor nuclei (see Chapter 12). Thus, the vestibulocerebellum has direct control of head and eye position via its influence on the vestibular nuclei.

The Pontine Nuclei Provide the Major Input to the Cerebrocerebellum

The pontine nuclei (Figure 13–12; also Figures 13–8 and 13–15B3, 4) relay information from the cerebral cortex to the cerebrocerebellum. Virtually the entire cerebral cortex projects to the pontine nuclei (see below). Corticopontine neurons originate in layer V of the cerebral cortex, the same layer that gives rise to the corticospinal and corticobulbar neurons. The descending axons course within the internal capsule and basis pedunculi to synapse in the ipsilateral pontine nuclei. The axons of neurons of the pontine nuclei decussate in the pons and enter the cerebellum via the middle cerebellar peduncle (Figure 13–12).

The Intrinsic Circuitry of the Cerebellar Cortex Is the Same for the Different Functional Divisions

The cellular constituents and synaptic connections of the cerebellar cortex are among the best understood of the central nervous system (see Box 13–1). The cerebellar cortex consists of three cell layers, progressing from its external surface inward (Figure 13–13): the molecular layer, the Purkinje layer, and the granular layer, which is adjacent to the white matter. The cerebellar cortex contains five types of neurons, and they each have a different laminar distribution and are excitatory or inhibitory (Figure 13–13B; Table 13–1): (1) Purkinje neuron, (2) granule neuron, (3) basket neuron, (4) stellate neuron, and (5) Golgi neuron. The Purkinje neuron is the projection neuron of the cerebellar cortex; it is located in the Purkinje layer. All others are interneurons.

The same two basic circuits are present throughout the cortex of the spinocerebellum, cerebrocerebellum, and vestibulocerebellum; one receiving excitatory input from the climbing and the other, from the mossy fibers. Climbing fibers originate entirely from the inferior olivary nuclear complex (Figure 13–11B) and synapse on Purkinje neurons (Figure 13–14). Climbing fibers make multiple synapses with one Purkinje neuron. Remarkably, each Purkinje neuron receives input from only a single climbing fiber. Individual climbing fibers branch to make contact with no more than about 10 Purkinje neurons.

The other circuit begins with the mossy fibers; the Purkinje neuron is also the target, but not directly (Figure 13–14). Mossy fibers first synapse on granule neurons—the only excitatory interneurons in the cerebellum. Located in the granular layer (Figure 13–13), granule neurons have an axon that ascends through the Purkinje layer into the molecular layer. Here the axon bifurcates to form the parallel fibers, which synapse on Purkinje neurons (Figure 13–14) and other cerebellar interneurons (Table 13–1). Note that the micrograph of the Purkinje neuron (Figure 13–14) is in the plane of the dendritic tree; the right side of the drawing is at right angles to the dendritic tree. Owing to the planar dendritic tree of Purkinje neurons, one parallel fiber will synapse only a few times with a Purkinje neuron, as the axon passes through its dendrites. That axon may synapse on hundreds of Purkinje neurons that are stacked along the folium. Each Purkinje neuron receives synapses from thousands of parallel fibers. The efficacy of parallel fiber input onto a given Purkinje neuron is increased immediately after Purkinje neuron activation by a climbing fiber. Purkinje neurons of the spinocerebellum and cerebrocerebellum project their axons through the cerebellar white matter to synapse on neurons in the deep cerebellar nuclei (Figure 13–12). To reach the vestibular nuclei, Purkinje neuron axons of the vestibulocerebellum travel through the inferior cerebellar peduncle.

The cerebellum is thought to have a modular functional organization organized, in part, by the projections of climbing fibers. Within the different sagittal functional zones (eg, Figure 13–5), there are microzones in which small clusters of Purkinje neurons receive climbing fiber inputs that have similar physiological characteristics, such as processing somatic sensory information from the same body part. The Purkinje neurons in the microzone, in turn, project to a group of neurons in a deep nucleus or vestibular nucleus that receive similar inputs from the olive. Within each functional division there are many microzones. It is thought that each microzone subserves a different aspect of the overall functions of the broader zone, such as regulating the coordination and strength of contraction of different hand muscles within arm representation of the spinocerebellum.

The Deep Cerebellar Nuclei Are Located Within the White Matter

The deep cerebellar nuclei can be identified in the transverse section through the pons and cerebellum shown in Figure 13–12, from medial to lateral: fastigial, globose, emboliform, and dentate nuclei. Recall that the globose and emboliform nuclei collectively are termed the interposed nuclei. The efferent projections of the deep nuclei course through the inferior and superior cerebellar peduncles.

The fastigial, interposed, and dentate nuclei have differential projections that reflect their functions in maintaining balance, controlling limb movement, and planning movement, respectively. The major targets of the output of the fastigial nucleus are the vestibular nuclei and the reticular formation, two components of the medial descending pathways that control balance and posture. The major targets of the interposed nuclei are the magnocellular division of the red nucleus, where the rubrospinal tract originates and, via the thalamus, the motor cortex. The major targets of the dentate nucleus are the parvocellular division of the red nucleus, which sends its axons to the ipsilateral inferior olivary nucleus via the central tegmental tract (shown at its termination in Figure 13–11A), and, via the thalamus, areas of cortex involved in motor planning. Note that the two divisions of the red nucleus cannot be clearly distinguished. The parvocellular division is much larger than the magnocellular division.

The ascending projections from the deep nuclei course in the superior cerebellar peduncle (Figures 13–12 and, 13–15B4). The superior cerebellar peduncle decussates in the caudal midbrain, at the level of the inferior colliculus (Figure 13–15A, B2). The axons continue rostrally, either synapsing with the two divisions of the red nucleus or passing through the nucleus en route to the motor thalamic nuclei. Collectively, the projections from the deep cerebellar nuclei to the thalamus are termed the cerebellothalamic tract.

The Ventrolateral Nucleus Relays Cerebellar Output to the Premotor and Primary Motor Cortical Areas

The portion of the thalamus that receives mostly cerebellar input and transmits this information to the motor areas of the frontal lobe, ventrolateral nucleus, is separate from the thalamic sensory nuclei. The ventrolateral nucleus (Figure 13–16) is difficult to identify. One clue that makes identification a bit easier is the presence of the thalamic fasciculus. This band of myelinated fibers contains axons of the cerebellothalamic tract as well as axons of the basal ganglia projection to the thalamus (see Chapter 14).

The ventrolateral nucleus is large and has many component divisions that have distinctive connections, primarily with the frontal lobe but also to the parietal lobe. The interposed and dentate nuclei project to the part of the ventrolateral nucleus that relays information mostly to the primary motor cortex (area 4) and the premotor cortex (lateral area 6). In addition, the dentate nucleus projects to other parts of the ventrolateral nucleus that project to posterior parietal cortex and the medial dorsal thalamus, which transmits information to the prefrontal cortex. The projections from the dentate nucleus interdigitate with but do not overlay the terminations from the interposed nuclei.

The Cerebellum Is Important for Many Nonmotor Functions

Transneuronal viral tracing studies in the monkey have revealed extensive connections between the dentate nucleus and diverse regions of the prefrontal and posterior parietal cortex, basically, nonmotor areas. These projections originate from the dentate nucleus. Routing through the thalamus, the projections target several regions within the prefrontal cortex and posterior parietal cortex. Whereas cerebellar damage in humans produces characteristic motor signs, as described earlier, damage of the posterior lobe can result in cognitive and affective changes. The projections of the cerebellum to prefrontal and posterior parietal cortex in monkey help to explain these nonmotor functions in the human. Also important for the nonmotor cerebellar functions are the descending corticopontine projections from cerebral cortical regions for cognition and affect (eg, Figure 13–7; discussed further below). In the monkey, only about 40% of the dentate nucleus is devoted to motor system connections. This leaves an intriguingly large portion of the nucleus for nonmotor connections and functions. Considering the increased complexity of the human brain, the nonmotor functions of the cerebellum—and the interplay between these functions and movement control—will very likely be an important direction for clinical and basic studies in the future.

The Corticopontine Projection Brings Information From Diverse Cortical Areas to the Cerebellum for Motor Control and Higher Brain Functions

Cerebral cortical regions to which the deep cerebellar nuclei project, via the thalamus, in turn project back to the cerebellum via the corticopontine projection (Figure 13–7). This forms a "closed loop," in which a particular functional region of the cerebellum, for example the hand control zone of the spinocerebellum, projects to an area of the cerebral cortex involved in the same function. We will see a similar predominantly closed loop organization for the basal ganglia (Chapter 14). There is little evidence for the alternative "open loop" organization, in which a cerebellar functional region communicates with cortical areas serving a different function.

In the human, diffusion tensor imaging (DTI; see Figure 2–7) has revealed that the densest of the corticopontine projections arise from the frontal lobe (Figure 13–17), which includes the primary motor cortex (area 4), the premotor areas (area 6) (see Figure 10–8), and the prefrontal association cortex. Additional projections also arise from association cortex in the parietal, occipital, and temporal lobes and from parts of the limbic cortical areas (which play important roles in emotions; see Chapter 16). Also using DTI, the topographic organization of the axons in the human basis pedunculi can be elucidated. Surprisingly, the largest region of the basis pedunculi contains descending axons from nonmotor areas (Figure 13–17). This amplifies what was discussed earlier, that the nonmotor functions of the cerebellum are likely to be very important.

Cerebellar Anatomy

The cerebellar cortex overlies the white matter (Figures 13–2 and 13–13). The cerebellar cortex contains numerous folia, which are grouped into three lobes (Figures 13–2 and 13–3): the anterior lobe, the posterior lobe, and the flocculonodular lobe. Embedded within the white matter of the cerebellum are four bilaterally paired deep nuclei, from medial to lateral (Figures 13–2 and 13–3): the fastigial nucleus, the globose nucleus, the emboliform nucleus, and the dentate nucleus. The globose and emboliform nuclei are collectively termed the interposed nuclei. The cerebellar cortex consists of three cell layers, from the cerebellar surface to the white matter (Figure 13–13): molecular, Purkinje, and granular layers. Five neuron classes are found in the cerebellar cortex (Figures 13–4 and 13–14; Table 13–1): (1) Purkinje neurons (Figures 13–4, 13–13, and 13–14), the projection neurons of the cerebellum—which are inhibitory; (2) granule neurons, the only excitatory interneurons in the cerebellum; and the (3) basket, (4) stellate, and (5) Golgi neurons—the three inhibitory interneurons.

Cerebellar Circuits

Two principal classes of afferent fibers reach the cerebellum to give rise to the two main circuits: climbing fibers (Figures 13–4 and 13–14), which are the axons of neurons of the inferior olivary nuclei (Figure 13–11B), and mossy fibers, which originate from numerous sources, including the pontine nuclei (Figure 13–15B4), reticular formation nuclei, vestibular nuclei (Figure 13–11), and spinal cord (Figure 13–11C). Most climbing and mossy fiber inputs are directed to both the deep cerebellar nuclei and the cerebellar cortex (Figure 13–4). The climbing fibers make monosynaptic connections with the Purkinje neurons; the mossy fibers synapse on granule neurons, which in turn synapse on Purkinje neurons via their parallel fibers. The Purkinje neurons project from the cerebellar cortex to the deep nuclei (Figure 13–12) and the vestibular nuclei (Figure 13–11).

Cerebellar Functional Divisions

The cerebellum is divided into three functional regions (Figures 13–2 and 13–5): the spinocerebellum, the cerebrocerebellum, and the vestibulocerebellum. Unilateral cerebellar damage produces ipsilateral limb motor signs due to decussation of cerebellar output pathways and decussation of the lateral motor pathways (Figure 13–10).

The spinocerebellum (Figures 13–6 and 13–7), which is important in posture and limb movement, is subdivided into two cortical regions that also have functional counterparts: The medial vermis subserves control of axial and girdle muscles, and the intermediate hemisphere controls limb muscles. The principal inputs to the spinocerebellum originate from the spinal cord. Somatic sensory information from the leg and lower trunk is transmitted to the cerebellum by the dorsal spinocerebellar tract (Figure 13–6A), via Clarke's nucleus, and from the upper trunk, arm, and neck, by the cuneocerebellar tract, via the accessory cuneate nucleus (Figure 13–11B). Other pathways convey internal feedback signals. Purkinje neurons of the vermis project to the fastigial nucleus (Figures 13–7 and 13–12), which influences medial descending pathways: the reticulospinal, vestibulospinal, and ventral corticospinal tracts. The projection to the lower brain stem is via the inferior cerebellar peduncle (Figure 13–11B), and the thalamic projection is via the superior cerebellar peduncle (Figure 13–15). The intermediate hemisphere projects to the interposed nuclei (Figure 13–12), which in turn influence the lateral descending pathways: the rubrospinal and lateral corticospinal tracts. All projections from the spinocerebellum course through the superior cerebellar peduncle.

The cerebrocerebellum (Figure 13–8) plays a role in planning movements; its cortical component is the lateral hemisphere. The cerebral cortex projects to the pontine nuclei (Figure 13–12), which provide the main input to the cerebrocerebellum. Purkinje neurons of this functional division project to the dentate nucleus (Figure 13–12). From there, dentate neurons project to the contralateral parvocellular red nucleus (Figure 13–15B1) and the ventrolateral nucleus of the thalamus (Figures 13–10 and 13–16), both via the superior cerebellar peduncle. The principal projections of the ventrolateral nucleus are to the primary motor cortex (area 4) and the premotor cortex (lateral area 6) (see Figure 10–7). The dentate nucleus also projects, via the thalamus, to the prefrontal and parietal association cortex to mediate nonmotor functions.

The vestibulocerebellum (Figures 13–5 and 13–9) is important in eye and head movement control; the cortical component corresponds anatomically to the flocculonodular lobe. It receives input from the vestibular nuclei and primary vestibular afferents and projects back to the vestibular nuclei via the inferior cerebellar peduncle (Figure 13–11B).