Motor learning in patients with cerebellar dysfunction.

Brain (1990), 113, 103-120

MOTOR LEARNING IN PATIENTS WITH CEREBELLAR DYSFUNCTION by JEROME N. SANES, 1 BOZHIDAR DIMITROV 2 and

MARK HALLETT

{From the Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA) SUMMARY This study examined whether cerebellar dysfunction resulted in deficiencies of motor learning. Patients with cerebellar atrophy only or cerebellar atrophy combined with atrophy of the brainstem and age-matched normal subjects performed two tasks to assess improvements in skilled performance. The first task was repetitive tracing with the hand of an irregular geometric pattern with normal visual guidance, and the second task was repetitive tracing of a different geometric pattern with mirror-reversed vision. Patients with pathology limited to the cerebellum showed impairments in the skilled performance of the movement performed with normal vision that may have been related to a failure to alter movement strategy. Patients with added pathology in the brainstem exhibited impairments in adapting to mirror-reversed vision. Subsidiary experiments indicated that improvements of movements guided by mirror-reversed vision were mediated by vision. These results indicate that the cerebellum and its associated input pathways are involved in motor skill learning. INTRODUCTION

Evidence has been accumulating that the cerebellum and its input and output pathways play a significant role in motor learning. The anatomical regularity and precision of the inputs to the Purkinje cells, the output neurons of the cerebellar cortex, suggest that the cerebellum could be a substrate for adaptive behaviour and especially motor learning (Brindley, 1964; Eccles et al., 1967). Marr (1969) hypothesized that the two main inputs to the Purkinje cells of the cerebellar cortex, the climbing and mossy fibres, provide distinctive signals in the establishment and maintenance of associative events. Marr (1969), and later Albus (1971), suggested that the climbing fibre inputs to the Purkinje cells, originating in the inferior olive, provide 'teaching' signals and that the mossy fibre inputs, originating in the pontine nuclei, provide important contextual information to form new associations based on the climbing fibre inputs to the Purkinje cells. Gilbert and Thach (1977) provided some indirect evidence for these theories by showing that complex spike activity of Purkinje cells, which reflects the climbing fibre input, is transiently increased in some cells when animals are actively adapting to a new movement situation. Evaluation of the cerebellar contribution to the plasticity of the vestibulo-ocular reflex and to the formation and retention of the classically conditioned nictitating membrane 1 Correspondence to: Dr Jerome N. Sanes, Center for Neural Science, Box 1953, Brown University, Providence, RI 02912, USA. 2 Permanent Address: Institute of Physiology, Bulgarian Academy of Sciences, Acad. G. Bontchev St., bl. 23, 1113 Sofia, Bulgaria.

© Oxford University Press 1990

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response has contributed significantly to understanding the role of the cerebellum in adaptive behaviour. Although the site of the 'plastic' synapse involved in vestibulo-ocular reflex adaptation has been suggested to be either in the flocculus (Ito, 1982) or the vestibular nuclei (Lisberger and Pavelko, 1986), it is nevertheless clear that cerebellar mechanisms are important in adaptation of visuomotor reflexes (Stone and Lisberger, 1986). Additionally, the work on the conditioned nictitating membrane response has generally supported the Marr-Albus models. In particular, stimulation of climbing fibres can act as an unconditioned teaching stimulus (Mauk etal., 1986), whereas stimulation of mossy fibres can act as a conditioned learning stimulus (Steinmetz et al., 1986; Lavond et al., 1987a). In contrast, lesions confined to the cerebellar hemisphere only transiently disrupt the acquisition and retention of the nictitating membrane response (Lavond et al., 1987b; but see Yeo et al., 1985). Thus, for the nictitating membrane response at least, the cerebellar cortex appears to integrate the major brainstem inputs but does not appear to be necessary for retention of the conditioned nictitating membrane response. There have been numerous descriptions of the deficits in voluntary and involuntary movement disorders of the limbs and eyes in humans with cerebellar dysfunction (Holmes, 1917, 1939; Hallett et al., 1975; Selhorst et al., 1976; Beppu et al., 1984, 1987; Friedemann et al., 1987; Sanes et al., 1988). In contrast, there has been a paucity of studies concerned with motor learning in these patients. Those studies that have been done have mostly been concerned with motor adaptation to altered visual environment (Gauthier et al., 1979; Weiner et al., 1983). In the latter study, cerebellar patients exhibited poorer than normal short-term adaptation when they wore distorting prisms and also had smaller than normal visuomotor after-effects when the prisms were removed. It is also likely that patients with cerebellar dysfunction have deficits in the learning of new skills, as suggested by Marr (1969). In the present study, we evaluated a series of patients with cerebellar disease on two tasks of skill acquisition, including one in which complex movements were made with reversed vision. METHODS Subjects Eleven patients, aged 18 — 70 (mean 48.5) yrs, presenting with clinical signs of cerebellar dysmetria in the upper extremities and 8 age-matched normal controls, aged 20—66 (mean 44.3) yrs, participated in these experiments. The patients were divided into two groups according to clinical and diagnostic criteria: group 1 consisted of patients with cerebellar hemisphere and/or vermis atrophy, and group 2 included patients with olivopontocerebellar atrophy syndrome (OPCA). The patients in group 1 were considered to have pathology limited to the cerebellum itself, whereas the patients in group 2 had atrophy both in the cerebellum and medullary and pontine regions of the brainstem. The patients' clinical descriptions are shown in Table 1. None of the patients exhibited tremor as a clinical symptom. Informed consent according to an NIH committee on human experimentation was obtained from all participants. All subjects were naive with respect to the design and goals of the study. Apparatus A GTCO digitizing tablet coupled with an electromagnetic stylus was used to measure reaching movements of the arm. The tablet, with its embedded electromagnetic search coil, had an active square-shaped


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MOTOR LEARNING IN CEREBELLAR DYSFUNCTION TABLE I. CLINICAL DESCRIPTION OF THE CEREBELLAR PATIENTS Case Age (yrs)/sex Diagnosis Group 1 (cerebellar hemisphere pathology) HI 55 F Cerebellar degeneration, autosomal recessive pattern H2 67 M Cerebellar degeneration, sporadic type H3 18M Cerebellar degeneration, sporadic type H4 70 M Cerebellar degeneration, sporadic type H5 29 M Cerebellar degeneration, sporadic type H6 67 F Cerebellar degeneration, autosomal dominant pattern H7 51M Cerebellar degeneration, alcoholic aetiology Group 2 (OPCA) 01 45 F OPCA, autosomal dominant pattern O2 56 F OPCA, sporadic type O3

56 F

OPCA, sporadic type

04

20 F

OPCA, sporadic type

Computed tomography.

b

Radiological findings Hemisphere and vermis atrophyb Slight hemisphere atrophya Diffuse cerebellar atrophyb Midline atrophy3 Hemisphere and vermis atrophyb Mild diffuse cerebellar atrophya Hemisphere and vermis atrophya

Cerebellar and brainstem atrophya Cortical atrophy with mild pontine atrophyb General cerebellar and pontine atrophyb Marked hemisphere and vermis atrophy; moderate atrophy of pons, medulla and upper spinal cordb

Upper limb alaxia Moderate Moderate Severe Moderate Moderate Mild Mild

Moderate Mild Moderate Moderate

Magnetic resonance imaging.

measurement field of 0.258 m2. The stylus, which emitted an electromagnetic wave and resembled a fountain pen, was used to evaluate the location of the hand by providing X and Y coordinates via an interface attached to the tablet. A glass plate was placed over the digitizing tablet, and the stylus was fitted with a nylon tip to allow it to slide with relatively low friction across the glass. The spatial accuracy of the system was nominally 0.25 mm, and spatial coordinates were digitized at 100 Hz. The tablet was mounted on a tilt table that was tilted at about 10° towards the subject. A frame mounted on the far end of the tilt table could hold a mirror that was used in the mirror adaptation experiments. For these experiments, the hand was hidden from direct view by having the subject place the right hand in a U-shaped wooden enclosure on the data tablet. Procedures Three separate experiments were conducted in two sessions, each lasting from 15 to 60 min. For each experiment, subjects traced with the point of the stylus an irregular geometric pattern that appeared on a piece of paper placed directly onto the tablet (fig. 1). Patients used the right hand throughout the motor skill evaluation. The patterns were sufficiently large so that subjects had to move more than the fingers and wrist to accomplish the task. Typically, the movement involved shoulder and elbow joint rotations, as well as adjustments of the wrist and occasionally the fingers. Speed of execution was emphasized as the most important movement parameter. Subjects were instructed to slide the stylus across the data tablet as rapidly as possible, but with the proviso that each movement segment begin and end in the small squares that enclosed each vertex of the pattern. Subjects were cautioned not to pause at the vertices, but rather to execute the movement in one continuous sequential movement. Subjects were informed that the lines


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FIG. 1. Patterns used for tracking movements, A, tracking pattern for movements with normal vision. For this and subsequent patterns, the asterisk is next to the starting position, and the arrow (not shown on the patterns viewed by the subjects) designates the requested direction of movement. The squares surrounding the vertices were target zones for the beginning and end of each segmental movement. B, pattern used for the first set of mirror tracking movements, c, pattern used for the second set of mirror tracking movements.

connecting the vertices were intended as a general guide for the sequential movement. In practice, most segments did begin and end in the squares, although this was not always evident for the highest velocity movements and for movements made with mirror vision. The room lights were dim at all times. No practice trials were allowed for any of the patterns. Subjects performed the series of sequential movements with typically no more than 5 s between successive movements, although longer rest periods were allowed at any time. In the first session, subjects traced a 5-vertex pattern (fig. 1A) with normal visual guidance for 50 movements. In the second session, subjects traced a 4-vertex pattern (fig. 1B) without direct visual guidance, but instead viewed the hand and the pattern with a mirror placed in front of them while performing 50 repetitions of moving around the 4-vertex pattern. Then a new 4-vertex pattern was presented (fig. lc), and they performed 10 additional movements with the mirror-reversed vision. One of the normal subjects was not tested with the 5-vertex pattern. Data from all cerebellar patients were collected successfully on all tasks. Data analysis X and Y coordinate data and the tangential velocity of the hand from each sequential movement were inspected on a computer display. Minima in velocity that corresponded to the end of one segment and to the beginning of the next movement segment were marked with an electronic cursor. The total movement time (MT, 10 ms resolution) required to complete the movement, the average, peak, and end-point error per segment, and the number of times the tangential acceleration crossed zero during the complete trajectory were obtained. This last measure was a crude indication of movement smoothness, insofar as repeated start-stop movements during the trajectory and even limb ataxia of significant magnitude would be reflected in an accumulation of zero crossings in the tangential acceleration profile. Average error was the sum of the perpendicular distance for each digitized X-Y sample from an ideal path between two vertices divided by the number of digitized sample points required to complete that segment. The procedure to calculate average error with respect to the number of sampled points was used to avoid inappropriate error scores due to the total time taken to complete the movement. If time was not considered in the calculation, then a trajectory that was, for example, 1 cm away from ideal and completed in 1 s (100 sample points) would have the same error score as a trajectory that was 0.5 cm away from ideal and completed in 2 s (200 sample points). If an observed coordinate was beyond the region in which a perpendicular distance could be obtained, then the straightline distance between the coordinate and the nearest vertex related to the movement segment was derived and summed to the total. No consideration was given to whether individual coordinates were inside or outside the pattern. The segmental errors were summed to derive error scores for the complete movement. Two separate repeated measures analyses of variance were done for each measured variable;


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one was for the first 15 trials and the other was for all 50 trials, blocked into groups of 5 trials each. These data were expressed as a percentage of the first trial (15 trial analysis) or the average of the first 5 trials (50 trial analysis). Linear correlation methods were used to compare the results from the first two experiments and for comparisons between MT and accuracy data or acceleration zero crosses. The rationale for using normalized data were twofold. First, there was a wide, and overlapping, range of response times and accuracy scores among the three groups and specifically a few patients showed very long times for the first few trials in the mirror adaptation task. Secondly, this investigation was concerned with the magnitude of behavioural change independent of a subject's performance level. Thus the absolute level of performance, because of overlapping scores, could have easily obscured any significant results in relation to behavioural adaptation. Despite our primary concern with relative scores, we do report the analyses of absolute performance. Unless noted, the data reported are on the normalized data. Reporting of the raw data values is prefixed with the word 'absolute'.

RESULTS

Normal vision The major features of the repetitive performance with normal vision are shown as sample trajectories in fig. 2 and as averaged data in fig. 3. The normal subjects and both patient groups decreased the MT needed to track the pattern with movement repetition (P < 0.05). However, the analysis of MT showed that the hemisphere patients differed from the normal subjects in performance across the 50 trials. For these patients, the MT scores decreased less than those of the normal subjects (P < 0.0002). The results of the MT analysis for the first 15 trials were similar to those for the 50 trials (fig. 3B). Although the normal subjects and both cerebellar groups showed improvements in MT over the 15 trials {P < 0.0001), the hemisphere patients exhibited a slower rate

fruils 41-50

FIG. 2. Movement trajectories with normal visual guidance, A, 10 superimposed movement trajectories from normal subject C51 from the first (left) and last (right) 10 movements performed with normal vision. The average time required to complete the track was 7.45 s for the first 10 movements and 4.71 s for the last 10 movements. B, 10 superimposed movement trajectories from Case H5 with a pure hemisphere lesion from the first (left) and last (right) 10 movements performed with normal vision. The average time required to complete the track was 9.58 s for the first 10 movements and 9.85 s for the last 10 movements. Accuracy was unchanged between the first and last 10 movements.



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•a

I

c B > o

10 15 20 25 30 35 40 45 Trial •a

M

g

>
0.79, P < 0.001, combined statistics for the three groups). Mirror vision The major features of performance with mirror-reversed vision are shown as sample trajectories from each of the three groups in fig. 5 and as averaged data in fig. 6. The first movements of all groups were slower than performance during the normal vision task. In addition, directional errors were common, especially during the first few trials. The segmental trajectories between the vertices, when performed without major errors in direction, were rarely straight, even for the normal subjects at the end of the 50 trials. Despite this deterioration in performance, in comparison to that observed during normal vision, the normal subjects and both patient groups decreased the total MT needed to track the pattern with movement repetition with mirror-reversed vision (P < 0.05). The OPCA patients did not improve their MT as much as the normal subjects or hemisphere patients (group by trial interaction, 50 trials, P < 0.05; 15 trials, P < 0.05, normal subjects only). However, and in contrast to the results on the normal vision task, the normalized MT performance of the hemisphere patients was nearly identical to that of the normal controls. The absolute MT values for the mirror reversal movements are shown in the right portions of Table 2. Initially, the OPCA patients had the fastest times, though by the last trials the normal subjects had improved their absolute MT to less than that for the Trial 1

Trial 5

Trial 10

Trial 50

FIG. 5. Trajectories during mirror-reversed vision, A, movements of normal subject C51 are illustrated, B, movements of Case H6 with hemisphere pathology are shown, c, movements of Case O4 with OPCA are depicted. The arrow in part A indicates the required initial direction of movement and each X symbol indicates the vertices of the pattern.


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5 10 15 20 25 30 35 40 45 L

1

5 10 15 20 25 30 35 40 45 L Trial

1 3

3

5

7 9 Trial

5

7 9 Trial

11

13

15

13

15

FIG. 6. Movement time and accuracy during mirror-reversed vision task, A, average MT to complete moving around the 5-vertex pattern. The normal and hemisphere groups showed decreased MT with repetition, B, average error during the complete track. No group showed increased error, c, average MT to complete the movement for each of the first 15 trials. Note that all groups reach the approximate asymptotic level of performance within the first 10 trials, D, average error for the first 15 trials. Note that the overall trend observed for all 50 movements was not apparent by performance of Trial 15 and that the variability amongst trials was high for each group. Error bars were omitted from some plots because of their large size. Symbols as in fig. 3.

OPCA group. The hemisphere patients were always slower than the OPCA patients, although their magnitude of improvement was greater than for the OPCA patients. There were no significant differences in the amount of average, peak, or end-point error between the normal and both cerebellar groups for performance during the 50 trials with mirror-reversed vision. In addition, there were no changes in average error with repetition of performance with mirror-reversed vision for any group. During performance on the first 15 trials, the average error of cerebellar hemisphere patients differed from the normal subjects (P < 0.05), insofar as the performance of the normal subjects was unchanged from the first to the fifteenth trial, whereas the average error of the hemisphere patients declined by about 40% from the first to the fifteenth trial. The number of zero crossings of the tangential acceleration profile during the mirror adaptation task paralleled the results for MT. Although all subjects showed a decrease



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in the number of acceleration zero crosses with repetition of the movement with mirror-guided vision (P < 0.05), there were significant differences between the groups of subjects. The reduction in the zero crosses of the OPCA patients was significantly less than that of the normal subjects (Patient x Repetition interaction, P < 0.01). Despite the large absolute number of acceleration zero crosses in the hemisphere patients, there was no difference between the patients and the normal subjects when reduction in the zero crosses was analysed. 1.0;

1.0

0.5-

0.5-

c

•S o.o

n

I

-0.5-

-1.0 J

Average error^\

End-point „ error MT

0.0

Average vs end-point error _ , _ O J

A Average error y

End-point yerror MT

Average vs end-point error

FIG. 7. Correlation analysis of performance variables during the mirror reversal task, A, comparisons for all 50 trials. B, comparisons for the first 15 trials. Ordinate axis label in B is the same as in A. *P < 0.05. Symbols as in fig. 4.

FIG. 8. Movement trajectories using the alternate pattern with mirror-reversed vision (see fig. lc). Representative trajectories of 3 normal (A), 3 hemisphere (B) and 3 OPCA (c) patients for the first in the series of 10 movements. Most subjects (except H3) made little or no error in the direction of the first movement segment as measured 3 cm from the starting point.


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The correlation analyses relating MT and average or end-point error in the mirror adaptation task are illustrated in fig. 7. The only significant correlation between MT and an error measure was for the hemisphere patients during performance of the first 15 trials (fig. 7B). Only the normal subjects had a significant correlation between average and end-point error during performance on all trials (fig. 7A). There were no significant correlations between average and end-point error during performance on the first 15 trials. MT and the number of zero crossings in the tangential acceleration profile (not illustrated) were highly correlated for all groups of subjects during performance with mirror-reversed vision (r > 0.81, P < 0.001, combined statistics for the three groups). First trial performance with a second pattern using mirror-reversed vision is shown in fig. 8. This pattern was rotated about 45° with respect to the original mirror-reversed pattern (fig. lc). Both the normal subjects and the patients, except possibly Case H3, moved in the correct direction and generally with the correct metric on the first trial when presented with this alternate pattern. The average angular deviation from an ideal trajectory of the first movement segment measured 3 cm from the starting point was 0.14±0.77° for the normal subjects, -1.33±3.53° for the OPCA patients, and 6.67 ±3.82° for the hemisphere patients. The patients' angular deviation from the expected trajectory did not differ from that of the normal subjects. Over the 10 trials done under mirror-reversed vision with the alternate pattern, there were no differences in the change of MT among the different subject groups. DISCUSSION

Many studies concerned with the role of the cerebellum in motor learning have focused on the acquisition and retention of simple reflexes or responses (Leaton and Supple, 1986; Thompson, 1986), adaptation of the vestibulo-ocular reflex (Ito, 1982; Lisberger et al., 1984), and in a few cases more complex behaviour involving visuomotor adaptation by humans (Gauthier et al., 1979; Weiner et al., 1983) or learning of a novel skill by monkeys (Gilbert and Thach, 1977). In general, these studies support the notion that cerebellar processes, either intrinsic or involving input or output structures of the cerebellum, are involved in adaptive, and long-term, processes of motor control. Others, however, have argued against a fundamental role for the cerebellum in the establishment of long-lasting associations for motor behaviour (Bloedel, 1987; Lou and Bloedel, 1988). The present results indicate that the cerebellum and related brain structures are involved in motor learning processes. Motor learning can be classified as motor skill acquisition and motor adaptation. The acquisition of a motor skill can broadly be defined as an improvement in the quality of motor performance, involving accuracy, speed, and a minimum of energy expenditure (Adams, 1987). Furthermore, skill, which is acquired, must be distinguished from the ability to perform, since individual skills often peak at different proficiency levels, although they presumably improve with repetition. These definitions of skill are closely related to voluntary motor behaviour and include the concept of acquiring a new motor ability. Motor adaptation, which includes changes in the vestibulo-ocular reflex and



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perhaps the speed-accuracy trade-off (Fitts, 1954), involves exchange of one behaviour for another in response to an alteration in either sensory inputs or task demands. We studied alteration of performance, especially the speed of movement, with repetition of relatively novel movements with normal and mirror-reversed vision, thus permitting assessment of motor learning. Acquisition of a motor skill has occurred when increases in speed are not simply related to a trade-off with accuracy (Fitts, 1954). Increases in speed of movement at the cost of accuracy might be considered motor adaptation. The aggregate performance strategy of the hemisphere patients differed from that of the normal and OPCA subjects on the normal vision task possibly because the dynamic range of their motor performance, especially regarding MT, is reduced under normal visual guidance conditions. This is supported by the observation that the hemisphere patients were initially operating at a higher speed than normal, and with a higher inaccuracy rate. Although both of these kinematic variables changed moderately with repetition, the diminution of the inverse changes in MT and accuracy, in comparison with normal and OPCA subjects, may have been associated with the hemisphere patients' inability to decrease their MT any further. The restriction of MT is supported by the absence of evidence that they could move faster than the time they showed at the end of the normal vision task. This could be related to the early suggestion that patients with pure cerebellar atrophy are bradykinetic (Holmes, 1917). Normally there is a trade-off between speed and accuracy in performance of movements with varying amplitude and accuracy requirements (Fitts, 1954). Thus faster movements are often performed with low accuracy, and movements with high accuracy requirements are often performed slowly. These relationships hold for patients with parkinsonism (Sanes, 1985). In the normal vision task, the normal subjects and 3 of the 4 OPCA patients showed the expected inverse relationships between MT and average or end-point error. These two groups of subjects did not exhibit motor skill learning in this task, but instead simply altered their performance strategy. This might be viewed as motor adaptation. In contrast, the patients with cerebellar hemisphere atrophy showed only modest, but qualitatively similar, changes in MT and accuracy by the fiftieth trial. Jerkiness of the movement trajectories may have contributed to the failure of cerebellar hemisphere patients and OPCA patients to improve their performance on the normal vision and mirror reversal tasks, respectively. One strategy for movement production is to minimize the rate of change of acceleration, or jerk (Nelson, 1983; Hogan, 1984). Indeed, trajectories performed under a minimum jerk strategy have an optimal smoothness (Flash and Hogan, 1985; but see Stein et al., 1988). Furthermore, in normal subjects, MT and jerk apparently decrease in parallel with repeated performance of the same movement (Schneider and Zernicke, 1989). Although we did not explicitly measure jerk, the number of zero crossings in the tangential acceleration profiles provides a crude measure of movement smoothness, or movement optimality. That is, a lower number of zero crossings would likely imply a more faithful reproduction of the target trajectory performed with uninterrupted segmental movements. The acceleration zero crossing data indicated that the hemisphere patients had less improvement in movement smoothness


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than normal subjects on the normal vision task and that the OPCA patients similarly had less improvement on the mirror adaptation task. These results paralleled those for MT, and may have been the causal factor in prolonging MT for the two cerebellar groups on the normal vision and mirror reversal tasks. The normal subjects showed improved speed but no changes in accuracy on the reversed vision task, a violation of the common performance law of reciprocal changes in speed and accuracy and evidence for true improvements in motor skill. The failure of the OPCA patients to match the MT performance of the normal subjects, and the absence of a change in accuracy for these patients during the mirror-reversed vision task can be interpreted not as a speed-accuracy trade-off but as a deficit in motor skill learning. Findings from studies concerned with modification of simple behavioural responses in animals with cerebellar pathology offer support for the involvement of the cerebellum and its input structures in the motor skill learning evaluated in the present study. The impairments in forming conditional associations found in animals with lesions to the input pathways of the cerebellum (McCormick et al., 1985; Lewis et al., 1987) could be related to the failure of OPCA patients to learn new associations between the apparent visual world, as distorted by the mirror, and conflicting information from planned movement trajectories and the ensuing kinaesthetic feedback. The associative properties of signals transmitted along either climbing or mossy fibre pathways are supported by observations that electrical stimulation of these pathways substitutes successfully for exteroceptive sensory stimuli that act as conditional or unconditional stimuli (Mauk et al., 1986; Steinmetz et al., 1986; Lavond et al., 1987a). Thus it is possible that the transformations necessary to resolve conflict between visual and kinaesthetic inputs gain access to the cerebellum via either climbing or mossy fibre pathways. Impaired resolution of sensory conflict in cerebellar patients might be related to general difficulties in integration of sensory information in cerebellar dysfunction. It is known that afferent information is transmitted to the cerebellum via climbing and mossy fibres (Gilman etal., 1981; Gellman etal., 1983, 1985; Glickstein etal., 1985; Kim et al., 1986). These inputs, and in particular somatosensory afferent information, may signal changes in environmental conditions (Gellman et al., 1983, 1985). The alterations of Purkinje cell activity due to inferior olivary input observed when monkeys were required to change the muscle activity needed to maintain a relatively static posture (Gilbert and Thach, 1977) could be related to novelty detection. Another possible role of the cerebellum is to integrate sensory inputs with motor commands (Chapman et al., 1986). In this regard, the ability to use visual guidance during ramp or step tracking movements is impaired in patients with cerebellar pathology (Beppu et al., 1984, 1987). The relative smoothness of the trajectories performed by the OPCA patients on the mirror reversal task was rather surprising. The smoothness was evident on their first trial, even though the performance of the normal and hemisphere patients was grossly impaired {see Trial 1 in fig. 5). The significance of these observations is uncertain, but may be related to deficits in visual information processing in the OPCA patients. Visual inputs that normally access the cerebellum via climbing and mossy fibres (Gilman



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etal., 1981) are probably compromised in OPCA patients. Thus, these patients, unlike normal subjects and cerebellar hemisphere patients, may not have to resolve the discrepancy between proprioceptive inputs and mirror-reversed visual information. Indeed, if OPCA patients rely mostly, but not exclusively, on proprioception for regulation of ongoing movements, then their initial trajectories would be smooth (Beppu, 1987; Sanes et al., 1988). However, the OPCA patients must have used visual information at least to process the directional requirements of the task. Thus it is possible that they used vision in a discrete sampling mode, but relied on proprioception for on-line movement regulation. Additionally, since improvements in skill on the mirror reversal task must entail resolution between the conflicting visual and proprioceptive inputs, patients without the initial conflict would not be expected to exhibit improvements in motor skill. Since the trajectories of the OPCA patients were not as smooth during the mirror reversal task as during the normal vision task, they also relied, but probably less than the normal and hemisphere subjects, on visual information to perform the movements with mirror-reversed vision. An inability to decrease MT below a minimum imposed by combined cerebellar and brainstem pathology may have kept the OPCA patients from additionally decreasing their MT during repetitive trials in the mirror reversal task. A floor effect that restricted MT would not necessarily explain their performance on the mirror reversal task, since the OPCA patients were able to move faster when they used normal vision than the time recorded at the end of the mirror reversal task {see Table 2). Despite this capability, and the observation that the decrease in absolute MT at the end of the mirror reversal task was comparable with that of the normal subjects, the proportionate decrease in MT at the end of the mirror reversal task was much greater for normal subjects than for OPCA patients. The MT results obtained with the second of two patterns used with mirror-reversed vision indicated that both groups of cerebellar patients, not only the hemisphere group, acquired some information about movements performed under altered visual conditions. Both groups of patients showed equal performance generalization to the new pattern after experience in moving around the first pattern. Further, the patients and normal subjects showed comparable performance on the first segment of the first movement. If, on the second pattern, they had made the first movement in the direction required by the first segment of the first pattern, we could have concluded that MT improvements with movement repetition in the mirror reversal task are dependent, in part, on knowledge of results derived from processing of kinaesthetic information or that all subjects used some visual information to make the movements. These results support the general conclusion that the cerebellum is involved in learning in the motor system. The patients with pathology limited to the cerebellum showed a deficit in the normal vision task that can be interpreted as their adopting a different strategy than normal controls and might be viewed as a failure of motor adaptation. The patients with combined cerebellar and brainstem atrophy, which probably altered transmission of information to the cerebellum via the climbing and mossy fibres, showed a deficit in the mirror-reversed vision task that can probably be interpreted as a failure


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in motor skill learning. It appears, as was postulated 25 years ago (Brindley, 1964), that the cerebellum contributes to learning of movement skills, but that the structures providing inputs to the cerebellum are critical in this process.

ACKNOWLEDGEMENTS We thank B. J. Hessie for skilful editorial assistance and the helpful suggestions of two anonymous reviewers.

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