Cerebellum
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).
