NEUR3101 Motor Control Lecture 10 - Cerebellum PDF

NEUR3101 Motor control Lecture 10 Cerebellum and motor control: learning & disorders A/Prof Ingvars Birznieks  Purves et al., Neuroscience (6th Ed) Chapter 19, Modulation of movement by the cerebellum. Kandel et al., Principles of Neural Science (5th Ed)...

NEUR3101 Motor control Lecture 10 Cerebellum and motor control: learning & disorders A/Prof Ingvars Birznieks  Purves et al., Neuroscience (6th Ed) Chapter 19, Modulation of movement by the cerebellum. Kandel et al., Principles of Neural Science (5th Ed) Chapter 42, The cerebellum  Overview Flourens (1824): “all movements persist following ablation of the cerebellum: all that is missing is that they are not regular and coordinated”. Comprises ~10% of the total brain by volume, but contains more than 50% of the number of neurons. Neurons arranged in a basic circuit that is repeated throughout the cerebellum. Divided into distinct regions which perform similar functions Jean Pierre Flourens 1794-1867 receive signals from different parts of the brain and spinal cord project to different motor systems  Cerebellum Regulates precise timing and appropriate patterns of skeletal muscle contraction. Involved in programming of ballistic movements. Detects discrepancy between intended and actual movement (“motor error”). Corrects ongoing movements based on internal & external feedback. These corrections can be made immediately during the course of the movement, or as a form of motor learning when the correction is stored in memory. Cerebellum Primary fissure Anterior Lobe Posterior Lobe Flocculo- nodular lobe (FN lobe) Folia  Functional divisions of the cerebellum Vestibulocerebellum – evolutionary oldest division controls balance and coordinates head-eye movements. Spinocerebellum - ongoing control of voluntary movement, posture and locomotion. - Vermis receives somatic sensory input (touch and proprioception). Cerebrocerebellum – evolutionary most recent, with the regulation of highly skilled movements, especially the planning, rehearsal and execution of complex spatial and temporal sequences of movement (including speech). Figure 19.1  Figures 19.1&2 Superior peduncle is almost entirely efferent pathway  Receives information regarding plans for movement from structures associated with programming and Input execution of movement. Receives information about motor performance from sensory feedback. Input from proprioceptors is relayed by the dorsal nucleus of Clarke and travels along the spinocerebellar tract. The inferior olive receives input from a wide variety of structures including the cerebral cortex, the reticular formation, and the spinal cord. Electrotonic gap junctions are abundant among neurons in the inferior olive, and these evidently play an important role in the timing of responses in the cerebellum. Figure 19.3  Somatotopic order The somatic sensory input remains topographically mapped in the spinocerebellum. The spinocerebellum contains at least two maps of the body. Unlike cerebrum, cerebellum holds ipsilateral representations. Figure 19.4 Thus, the topographical organization of the cerebellum would explain that cerebellar damage may disrupt the coordination of movements performed by some muscle groups but not the others. Regular alcohol abuse may cause damage to the vermis specifically affecting movement in lower limbs. The consequences include a wide and staggering gait, but with relatively little impairment of arm or hand movements. Output to the cortex The output from the cerebellar cortex is relayed via deep cerebellar nuclei. Adjusts outputs of descending motor pathways by projections to the motor cortex via thalamus. Sends projections to virtually all upper motor neurons. Figure 19.6 Output to the brainstem motor systems  Circuits within the cerebellum Figure 19.9 This basic circuit is repeated over and over throughout every subdivision of the cerebellum in all mammals. It is the fundamental functional module of the cerebellum.  Circuits within the cerebellum Purkinje cells The main output cells integrating information in the cerebellum. Mossy fibres The axons from the pontine nuclei and most other sources of cerebellar input from the cerebral cortex, and spinal cord are called mossy fibres because of the appearance of their synaptic terminals. They have access to the Purkinje cells only via parallel fibres of granule cells. Parallel fibres Parallel fibres of granule cells bifurcate in the molecular layer to form T-shaped branches that extend for several mm parallel to the surface. Purkinje cell dendrites branch extensively in a plane at right angles to the trajectory of the parallel fibres. Each Purkinje cell receives input from a large number of parallel fibres (about 200,000), and each parallel fibre can contact a very large number of Purkinje cells (on the order of tens of thousands). Figure 19.9  Circuits within the cerebellum Climbing fibres Purkinje cells also receive a direct modulatory input on their dendritic shafts from the climbing fibres, all of which come from the inferior olive located in the medulla oblongata (note that superior olive in contrast is involved in auditory processing). Each Purkinje cell receives about 1000 (!) synaptic contacts from a single climbing fibre. Climbing fibres provide a "training“ signal” that modulates the effectiveness of the parallel fibre connection with the Purkinje cells. Local circuits Golgi cells form an inhibitory feedback circuit that controls the gain of the granule cell input to the Purkinje cells. Basket cells provide lateral inhibition that may focus the spatial distribution of Purkinje cell activity. Figure 19.9  Circuits within the cerebellum The Purkinje cells project to the deep cerebellar nuclei. They are the only output cells of the cerebellar cortex. Since Purkinje cells are GABAergic, the output of the cerebellar cortex to deep cerebellar nuclei is wholly inhibitory. Neurons in the deep cerebellar nuclei also receive excitatory input from collaterals of the mossy and climbing fibres. The inhibitory projections of Purkinje cells serve to shape the discharge patterns that deep nuclei neurons generate in response to direct mossy and climbing fibres input. Figure 19.10  Circuits within the cerebellum The deep cerebellar nuclei receive excitatory inputs from the mossy and climbing fibres, in the same time their activity patterns are sculpted by the descending inhibitory inputs of Purkinje cells, which are driven by these same two pathways. For their part, Purkinje cells integrate these principal inputs and invert their "sign" by responding to excitatory drive with an inhibitory output. Thus, Purkinje cells convey the product of computations performed by an inhibitory loop that comprises the circuitry of the cerebellar cortex. Figure 19.10  Motor learning Figure 19.13 Learned changes in the vestibulo-ocular reflex in monkeys Normally, this reflex operates to move eyes as head moves, so that the retinal image remains stable. When the animal observes the world through minifying spectacles, the eyes initially move too far with respect to the “slippage” of the visual image on the retina.  Motor learning Figure 19.13 After some experience, however, the gain of the VOR is reset and the eyes move an appropriate distance in relation to head movement, thus compensating for the altered size of the visual Image. If the cerebellum is damaged or removed, the ability of the VOR to adapt to the new conditions is lost. These observations support the conclusion that the cerebellum is critically important in error reduction during motor learning.  Pain avoidance behaviour Cerebellum is involved in nociceptive processing. The cerebellum receives nociceptive input from both descending cortico-cerebellar pathways and ascending spino-cerebellar pathways, through the pontine nuclei and inferior olives. Some of this information is used to learn how to perform movement and minimise nociceptive inputs. In healthy individuals this facilitates learning of most efficient and injury free way to perform movement. Nociceptive inputs driving these behavioural adjustments should not necessarily be consciously perceived. In case of musculoskeletal injury or even internal organ dysfunction this mechanism may induce persisting pathologic movement patterns or may result in chronic postural changes. In long term this causes more damage than good. Therefore physiotherapeutic intervention is required.  Motor learning Cerebellar Normal infarction Before Before Prisms Prisms After After Darts Kandel, Figure 42.13  Typical signs of cerebellar damage Kandel, Figure 42.1 A. A lesion in the left cerebellar hemisphere delays the initiation of movement. The patient is told to clench both hands at the same time on a “go” signal. The left hand is clenched later than the right, as is evident in the recordings from a pressure bulb transducer squeezed by the patient. B. A patient moving his arm from a raised position to touch the tip of his nose exhibits inaccuracy in range and direction (dysmetria) and moves his shoulder and elbow separately (decomposition of movement). Tremor increases as the finger approaches the nose. This is called intention or action tremor. C. A subject was asked to alternately pronate and supinate the forearm while flexing and extending at the elbow as rapidly as possible. Position traces of the hand and forearm show the normal pattern of alternating movements and the irregular pattern (dysdiadochokinesia) typical of cerebellar disorder.  Typical signs of cerebellar damage Hypotonia – decreased resistance to passive movement, pendular reflexes. Slow corrective movements. Cerebellar ataxia – jerky imprecise movement, lack of muscle coordination, errors in the range and force of movement (dysmetria, dysdiadochokinesia), problems with multi-joint movements. Delay in initiating movements, but no problem to initiate goal directed movement. Difficulty performing rapid alternating movements, distorted timing in movement sequences and impaired sequence learning. Intention tremor – is one type of action tremor seen during movement, particularly at movement endpoint characterised by impaired accuracy. Dysarthria – impairment of speech production due to motor dysfunction. Gait impairment – wide-based stance, ataxic gait. Alcoholism can affect vermis. Such damage specifically affects movement in the lower limbs, which are represented in the anterior spinocerebellum. Movement errors are always on the same side of the body as the damage to the cerebellum, reflecting the cerebellum's unusual status as a brain structure in which sensory and motor information is represented ipsilaterally rather than contralaterally.