Strick Lecture 3 March 22, 2017 Page 1

Size: px

Start display at page:

Download "Strick Lecture 3 March 22, 2017 Page 1"

Louise Gregory
6 years ago
Views:

1 Strick Lecture 3 March 22, 2017 Page 1 Cerebellum OUTLINE I. External structure- Inputs and Outputs Cerebellum - (summary diagram) 2 components (cortex and deep nuclei)- (diagram) 3 Sagittal zones (vermal, paravermal and lateral) II. III. IV. Internal structure- wiring diagram Cell and afferent fiber types (diagram) Cerebellar disorders (Neurophysiological basis) a. Hypotonia (diagram) b. Delayed onset and termination of movement (also reduction in force) (diagram) c. Decomposition of movement (diagram) d. Tremor (diagram)(videotape segment) Examples of Cerebellar Function - Adaptive Control a. Cerebellar Adaptive Control of Posture b. Orbital Position Dependent Dysmetria c. Prism adaptation I. Cerebellum - is the mass of neurons sitting above the pons and medulla Overview - (summary diagram, Fig. 3-1) Cerebellar inputs: Diverse. Originate from multiple cortical areas and from spinal cord ascending systems. Cerebellar output: Via the ventrolateral thalamus to cortical motor areas and to areas of prefrontal and posterior parietal cortex (new concept). The Cerebellum consists of 2 components: Cerebellar Cortex and the Deep Cerebellar Nuclei External structure, Inputs and Outputs Cerebellar Cortex- (Fig. 3-2) A. Transverse Organization = Lobes - Lobules - folia 3 major lobes= anterior, posterior and flocculonodular - the primary fissure separates the anterior and posterior lobes; - the posterolateral fissure separates the posterior and flocculonodular B. Sagittal Organization (the most functionally relevant scheme) 3 zones: 1 = Vermus zone (midline zone) 2 = intermediate zone (or paravermal zone) 3 = lateral zone [Hemisphere = intermediate and lateral zones] Deep Nuclei- (Fig. 3-3)

2 Strick Lecture 3 March 22, 2017 Page 2 Each zone of cerebellar cortex projects to a different deep cerebellar nucleus (i.e., 3 zones - 3 deep nuclei) A. the vermal zone projects to the Fastigial nucleus B. the paravermal cortex (intermediate cortex) projects to the Intermediate nucleus = the interpositus nucleus of primates = the globose (medial and posterior) and the emboliform (lateral and anterior) nuclei of humans C. the lateral cortex projects to the Dentate nucleus Functionally, there are 3 Cortico-nuclear zones- Different effects are produced by stimulation or lesions of each zone: medial = intermed= lateral = effects on whole body posture and locomotion effects on the control of distal movements effects are still somewhat of a mystery, but both distal and proximal movements are involved. The flocculonodular lobe is often considered as part of the medial zone. It is involved in vestibular and oculomotor functions. Given this sagittal organization, remember to ask where the lesion is when someone talks about a cerebellar patient. We will focus on the skeletomotor functions of the cerebellum. However, cerebellar involvement in behavior is wide-ranging. There is evidence for cerebellar control of attention, cardiovascular function, respiration, feeding behavior, sleep, speech, and possibly memory. II. Cerebellum - Internal structure (Fig. 3-4) Cortex types of afferent fibers: mossy fibers and climbing fibers 2. 5 cell types: Purkinje cell, granule cell, golgi cell, stellate cell, basket cell 3. 1 output cell: Purkinje cell We will focus on the circuits involving Purkinje, granules and the two types of afferent inputs. Mossy fibers originate from multiple sources, i.e., pons, spinal cord, etc. Mossy fibers make contact with granule cells. The axons of granule cells ascend to the outer molecular layer of cerebellar cortex and form parallel fibers. These parallel fibers run for considerable distances and make contact with the dendritic spines of many Purkinje cells. Thus, a single mossy fiber influences many Purkinje cells and a single Purkinje cell receives input from many mossy fibers. Climbing fibers originate from a single source (inferior olive). Only one climbing fiber contacts each Purkinje cell. If you record from Purkinje cells:

3 Strick Lecture 3 March 22, 2017 Page 3 1) The activity of a climbing fiber produces a complex spike in a Purkinje cell. 2) In contrast, the activity of a mossy fiber input evokes simple spikes in Purkinje cells. Recordings of complex spike and simple spike discharge in awake animals show (Fig. 3-5) Slide 6 1) Climbing fiber discharge = irregular and infrequent, often not well-related to movement = "infrequent" error signal 2) Mossy fiber discharge = spontaneously active, modulates with somatosensory or motor signals = "moment by moment" signal Current concept- Climbing fiber activity modifies the response of a Purkinje cell to subsequent parallel fiber input = Basis of Motor Learning. Temporal coincidence of climbing fiber input with parallel fiber input will modify the response of a Purkinje cell to subsequent parallel fiber input. It is still unclear whether the Purkinje cell becomes more or less responsive to a parallel fiber input. III. Cerebellar disorders (Neurophysiological basis)(fig. 3-6) Cerebellar dysfunction leads to 6 basic motor problems: a) hypotonia, reduced force production, delayed onset and termination of movement, intention tremor, hypo- and hypermetria, movement decomposition. A. Hypotonia (Fig. 3-7) = reduced response to perturbations, reduced ability to maintain tone Neurophysiological basis (a disorder in the cerebello-thalamocortical pathway): I. Cerebellar lesion reduces tonic excitability of M1 1. cerebellum output projects to VL; VL projects to the primary motor cortex 2. neurons in the deep cerebellar nuclei have relatively high tonic rates of discharge 3. If this tonic input to the primary motor cortex is removed, then the excitability of the primary motor cortex is decreased. and/or II. Cerebellar lesion removes a source of signal for corrective response 1. the cerebellum receives a signal from periphery that there has been a perturbation 2. the signal reaches primary motor cortex and generates a corrective response 3. a lesion of cerebellum reduces or abolishes this signal B. Delayed onset and termination of movement (also reduction in force) (Fig. 3-8) Neurophysiological basis: The relation between dentate and interpositus neuron activity and movement onset DENTATE 1. neurons in the primary motor cortex discharge before movement 2. neurons in the dentate nucleus also discharge before movement 3. dentate neurons are thought to be a source of the central commands for initiating motor cortex activity and movement 4. dentate lesions delay movement onset by 100 msec, but movement occurs INTERPOSITUS 1. neurons in interpositus (globose and emboliform of the human) discharge at or just after movement onset. 2. Thus, these neurons are not likely to be involved in the process of movement initiation

4 Strick Lecture 3 March 22, 2017 Page 4 3. However, they may be involved in movement termination or correcting errors during the course of movement 4. Interpositus lesions do not cause a delay in movement onset C. Tremor (Fig. 3-9) Slide 10, particularly at the onset and termination of movement Types of Cerebellar tremor- Intention tremor, e.g., finger to nose test Postural tremor, e.g., ataxia One viewpoint is that intention tremor is actually successive overshoots and undershoots about a goal which leads to oscillation, i.e., a type of dysmetria. EMG basis of Dysmetria (Fig. 3-10) For a movement to be accurate, both the size and the duration of the Agonist and Antagonist bursts must be precisely adjusted in amplitude and timing. For example- - if the Agonist is too large = movement would be hypermetric - if the Agonist is too small = movement would be hypometric -similar problems would arise if the amplitude of the antagonist burst were not properly adjusted -in addition, bursts that are too long or short in duration would lead to dysmetria D. Decomposition of movement (Fig. 3-11) Definition: Test: a breakdown in the correct spatio-temporal features of simple movement sequences. Examine the ability to produce repeatable sequences of rapidly alternating movements. EMG basis (Fig. 3-10): (elemental deficit) 1. Normal subjects display a decrease in activity in antagonist muscles prior to any change in agonist activity 2. This decrease has been termed the Huffschmidt phenomenon 3. Some patients with cerebellar lesions lack the Huffschmidt phenomenon 4. Thus, these subjects are unable to turn off muscle activity that opposes their movement. Also No "Sequence Length Effect" in cerebellar patients (higher order deficit) 1. Normal subjects show an increase in the reaction time to perform the first movement in a sequence as the number of elements in the sequence increases = "sequence length effect" (Fig. 3-12) 2. Cerebellar patients do not show this effect 3. In cerebellar patients, each element in a sequence is performed as if it was a reaction time task. 4. The interbutton interval is prolonged in cerebellar patients 5. Thus, cerebellar patients are unable to quickly and easily perform one movement right after another without a reaction time between each movement.

5 Strick Lecture 3 March 22, 2017 Page 5 This is a higher-order motor deficit. Cerebellar output is directed at primary motor and premotor areas. The absence of a "sequence length effect", the prolonged interbutton intervals and reaction time delays reflect a difficulty in combining simple movements together into a sequence. This may be due to interruption of cerebellar input to premotor areas involved in higher order aspects of motor programming. IV. Examples of Cerebellar Function - Adaptive Control Figure 1 a. Cerebellar Adaptive Control of Posture (Fig. 3-13, 3-14, 3-15, 3-16) b. Orbital Position Dependent Dysmetria (Fig. 3-17) c. Prism Adaptation (Demonstration)

6 Strick Lecture 3 March 22, 2017 Page 6 Figure 2 Figure 3

7 Strick Lecture 3 March 22, 2017 Page 7 Figure 4

8 Strick Lecture 3 March 22, 2017 Page 8 Figure 5 Figure 6

9 Strick Lecture 3 March 22, 2017 Page 9 Figure 7 Figure 8

10 Strick Lecture 3 March 22, 2017 Page 10 Figure 9 Figure 10

11 Strick Lecture 3 March 22, 2017 Page 11 Figure 11 Figure 12

12 Strick Lecture 3 March 22, 2017 Page 12 Figure 13 Figure 14

13 Strick Lecture 3 March 22, 2017 Page 13 Figure 15 Figure 16

14 Strick Lecture 3 March 22, 2017 Page 14 Figure 17 Figure 18

15 Strick Lecture 3 March 22, 2017 Page 15 Figure 19

16 Strick Lecture 3 March 22, 2017 Page 16 Figure 20

The Cerebellum. Outline. Lu Chen, Ph.D. MCB, UC Berkeley. Overview Structure Micro-circuitry of the cerebellum The cerebellum and motor learning

The Cerebellum. Outline. Lu Chen, Ph.D. MCB, UC Berkeley. Overview Structure Micro-circuitry of the cerebellum The cerebellum and motor learning The Cerebellum Lu Chen, Ph.D. MCB, UC Berkeley 1 Outline Overview Structure Micro-circuitry of the cerebellum The cerebellum and motor learning 2 Overview Little brain 10% of the total volume of the brain,