Organization of the cerebellum
The cerebellum (CBM) is a complex structure found below the tentorial membrane in the posterior fossa and connected to the brainstem by three pairs of (cerebellar) peduncles (see Chapter 8). It is primarily involved in the coordination and learning of movements, and is best thought of in terms of three functional and anatomical systems:
• spinoCBM – involved with the control of axial musculature and posture + ;
• pontoCBM – involved with the coordination and planning of limb movements ;
• vestibuloCBM involved with posture and the control of eye movements .
These three systems have their own unique pattern of connections (see Table 40.1).
• The spinoCBM can be divided into a vermal and paravermal (intermediate) region with the former having a close association with the axial musculature. It is therefore associated with the ventromedial descending motor pathways and motor neurones (MNs) while the paravermal part of the spinoCBM is more concerned with the coordination of the limbs.
• The pontoCBM has a role in this coordination but is associated with the visual control of movement and relays information from the posterior parietal cortex to the motor cortical areas.
• The vestibuloCBM has no associated deep cerebellar nucleus and is phylogenetically one of the oldest parts of the cerebellum. Like the vermal part of the spinoCBM, it is involved with balance through its connections with the ventromedial motor pathways but also has a role in the control of eye movements (see Chapter 56).
Longterm depression (LTD) and motor learning
In general, the CBM compares the intended movement originating from the motor cortical areas with the actual movement as relayed by the muscle afferents and spinal cord interneurones, while receiving an important input from the vestibular and visual system. The comparison having been made, an error signal is relayed via descending motor pathways, and the correction factor stored as part of a motor memory in the synaptic inputs to the Purkinje cell
(PuC). This modifiable synapse at the level of the PuC is an example of long-term depression (LTD; see Chapters 45 and 49). It describes the reduced synaptic input of the parallel fibre (pf) to PuC when it is activated in phase and at low frequency with the climbing fibre input to that same PuC and persists at least for several hours. In other words, at times of new movements the climbing fibre input to the PuC increases which has a modifying effect on the pf input to that same PuC. As the movement becomes more routine, the climbing fibre (cf) lessens but the modified (reduced) pf input persists: it is this modification that is thought to underlie the learning and memory of movements.
This modifiable synapse was first proposed by Marr in 1969 and subsequently has been verified, especially with respect to the vestibulo-ocular reflex (see Chapter 49). The biochemical basis of LTD in the CBM is unknown but appears to rely on the activation of different glutamate receptors in the PuC and the subsequent influx of calcium and the activation of a protein kinase. The presence of a modifiable synapse implies that the CBM is capable of learning and storing information in a motor memory (see Table 40.1).
The microscopic organization of the cerebellum
The microscopic organization of the cerebellum, which allows for the generation of LTD, is well characterized even if the biochemical basis for it remains obscure. The excitatory input to the cerebellum is provided by a mossy and climbing fibre input. The mossy fibre indirectly activates PuC through parallel fibres that originate from granule cells (GrC). In contrast, the climbing fibre directly synapses on the PuC and, as with the mossy fibre input, there is an input to the deep cerebellar nuclei neurones (DCNNs). These neurones are therefore tonically excited by the input fibres to the cerebellum, and are inhibited by the output from the cerebellar cortex (the PuC). The PuC in turn are inhibited by a number of local interneurones, while Golgi cells (GoC) in the outer granule cell layer provide an inhibitory input to the GrC. All of these interneurones have the effect of inhibiting submaximally activated PuC and GrC, and by so doing highlight the signal to be analysed.
The final output of the cerebellum from the deep cerebellar nuclei to various brainstem structures is also inhibitory.
Functional and anatomical systems of the cerebellum
Clinical features of cerebellar damage
Much that can be deduced about the function of the CBM is derived from the clinical features of patients with cerebellar damage.
Dysfunction of the CBM is found in a large number of conditions, and the clinical features of cerebellar damage are as follows:
• Hypotonia or reduced muscle tone. This is caused by a reduced input from the DCNN via the descending motor pathways to the muscle spindle (see Chapter 36).
• Incoordination/ataxia. There are a number of manifestations of this including: asynergy (an inability to coordinate the contraction of agonist and antagonist muscles); dysmetria (an inability to terminate movements accurately which can result in an intention tremor and past pointing); and dysdiadochokinesis (an inability to perform rapidly alternating movements). Ataxia is often used to describe incoordinated movements. In cases where the vermis is predominantly involved, as occurs in alcoholic cerebellar degeneration, this results in a staggering, wide-based, ‘drunk-like’ character to the gait. When there is involvement of the more lateral parts of the cerebellar hemisphere the incoordination involves the limbs.
• Dysarthria. This is an inability to articulate words properly caused by incoordination of the oropharyngeal musculature. The words are slurred and spoken slowly (scanning dysarthria).
• Nystagmus. This describes rapid jerky eye movements caused by a breakdown in the outflow from the vestibular nucleus and its connections with the oculomotor nuclei (see Chapters 29 and 56).
• Palatal tremor or myoclonus. This is a rare condition in which there is hypertrophy of the inferior olive, with damage in a triangle bounded by this structure, the dentate nucleus of the CBM and the red nucleus in the midbrain (Mollaret triangle). The patient characteristically has a low-frequency tremor of the palate, which oscillates up and down.
Finally, there is a recent suggestion that the cerebellum may also subserve some cognitive function, as subtle deficits can be seen in this domain in some patients with cerebellar disease.
Function of the cerebellum
The role of the CBM can be defined by area and correlates well with the localizing signs of cerebellar disease. Exactly how the CBM achieves these functions is unknown, but the repetition of the same elementary circuitry in all parts of the cerebellar cortex implies a common mode of function. Three possibilities exist which are not mutually exclusive.
• By acting as a comparator. The CBM compares the descending supraspinal motor signals (efference copy, intended movement) with the ascending afferent feedback information (actual movement), and any discrepancy is corrected by the output of the CBM through descending motor pathways. This allows the CBM to coordinate movements so that they are achieved smoothly and accurately.
• By acting as a timing device. The CBM (especially the pon- toCBM) converts descending motor signals into a sequence of motor activation so that movement is performed in a smooth and coordinated fashion, with balance and posture maintained by the vestibule and spinoCBM.
• By initiating and storing movements. The existence of a modify able synapse at the level of the PuC means that the CBM is capable of storing motor information and updating it. Therefore, under the appropriate circumstances, the right sequence for a movement can be accessed and fed through the supraspinal motor pathways, and by so doing an accurate learnt movement is initiated (see also Chapter 35).