Coordination of a multi-joint movement in normal humans and in patients with cerebellar dysfunction

The contribution of the cerebellar cortex to coordination of a multi-joint throwing movement was studied by measuring various movement and EMG parameters while normal control subjects and patients with cerebellar cortical atrophy threw a ball at a target. Although patients did not throw as accurately as controls, several coordination measurements were normal in the patients. These included parameters used by us to assess elbow-wrist coordination and the coordination of hand opening with activation of more proximal arm muscles. Postural support for the movement at the shoulder was also normal in that the shoulder was not pushed backwards by the reaction forces resulting from the rapid forward acceleration of the forearm and hand. In contrast, however, patients were unable to coordinate the muscles so as to produce the same hand direction from trial to trial when throwing at the same target. In addition, EMG onset times were abnormal in the antagonist muscles relative to agonist EMG bursts and kinematic parameters of the movement. In conclusion, our patients with cerebellar cortical atrophy showed abnormalities in visual-motor coordination, in that they were unable to consistently produce the appropriate hand direction in response to a visual target. Agonist-antagonist relationships were also impaired. Other aspects of coordination, such as the relative timing of EMG onsets of agonist muscles, even when these were active at different joints, were normal.     

Hand orientation for grasping and arm joint rotation patterns in healthy subjects and hemiparetic stroke patients

We previously demonstrated that the hand orientation for grasping (azimuth) is strongly coupled to arm movement direction in the horizontal plane. The question is whether this coupling is directly controlled or secondary to a regulation of the arm angular configuration. To this purpose, we quantified hand orientation and arm joint rotations during unconstrained reaching movements in healthy subjects and in patients with hemiparesis due to stroke since they use altered joint rotation patterns for reaching. Seven healthy subjects and eight patients with a right hemiparesis participated (four had a moderate and four had a mild disorder). Four electromagnetic sensors were used to measure hand orientation and to compute the wrist, elbow and shoulder joint angles. Hand azimuth at the time of grasping was correlated to arm movement direction in all the healthy and hemiparetic individuals. In healthy subjects, a regression analysis of the arm joint rotations suggested that the coupling between hand azimuth and movement direction was not due to a correlation with a particular degree of freedom. Patients used different hand orientations for grasping and different joint rotation patterns that varied according to their level of disability and the use of compensatory strategies. The findings observed in both healthy subjects and patients with stroke show that the coupling of hand azimuth for grasping to movement direction was controlled independently of the set of joint rotations used for reaching. This suggests that it is a basic synergy directly controlled by the motor system.     

Representation of accuracy in the dorsal premotor cortex

The endpoint accuracy of a reaching movement strongly affects kinematics, particularly during the final phases of movement. However, where and how accuracy is represented in the central nervous system remains unknown. In this study, the discharge of 150 neurons located primarily in the dorsal premotor cortex (PMd), were recorded from monkeys performing an instructed delay, centre-out reaching task in which movement direction and target size were systematically varied. Linear regression analyses were used to assess the dependence of movement kinematics and cell discharge on target direction, size and tangential velocity (i.e. speed). The speed and timing of the movement were dependent on both direction and target size. Initially direction was the dominant predictor whilst target size became more important as the hand reached the target. A temporal multiple linear regression analysis found significant correlations with target size in 99 of 150 cells. The discharge of 134 cells was directionally tuned and 83 cells modulated with mean speed. Significant correlations of discharge with target size occurred throughout the task as did correlations with direction. However, correlations with direction preferentially occurred early in the task, prior to movement onset, whilst correlations with target size tended to occur late, well after movement onset. This temporal dependency of the firing in relationship to target direction and size mirrored that observed for the kinematics. We conclude that the discharge of PMd cells is highly correlated with the accuracy requirement of the movement. The timing of the correlations suggest that accuracy information is available for the planning and for the on-line control of endpoint accuracy.     

Three-dimensional tuning profile of motor cortical activity during arm movements

The neural firing activity in the primary motor cortex was modulated to the direction of hand movement. In contradiction to previous reports, a recent study found a non-uniform distribution of preferred directions of neurons while monkeys made center-out reaching movements in a horizontal plane. To re-examine the distribution of preferred directions in three-dimensional space, we recorded the activity of 117 arm-related neurons in the primary motor cortex and electromyographic signals of shoulder and upper arm muscles of a monkey while it performed center-out reaching movements towards 26 target points placed on a sphere-shaped workspace. We found that the distribution of preferred directions of neurons was non-uniform and that it was correlated to muscle activity and arm joint rotations.     

Proprioceptive Localization Deficits in People With Cerebellar Damage

It has been hypothesized that an important function of the cerebellum is predicting the state of the body during movement. Yet, the extent of cerebellar involvement in perception of limb state (i.e., proprioception, specifically limb position sense) has yet to be determined. Here, we investigated whether patients with cerebellar damage have deficits when trying to locate their hand in space (i.e., proprioceptive localization), which is highly important for everyday movements. By comparing performance during passive robot-controlled and active self-made multi-joint movements, we were able to determine that some cerebellar patients show improved precision during active movement (i.e., active benefit), comparable to controls, whereas other patients have reduced active benefit. Importantly, the differences in patient performance are not explained by patient diagnosis or clinical ratings of impairment. Furthermore, a subsequent experiment confirmed that active deficits in proprioceptive localization occur during both single-joint and multi-joint movements. As such, it is unlikely that localization deficits can be explained by the multi-joint coordination deficits occurring after cerebellar damage. Our results suggest that cerebellar damage may cause varied impairments to different elements of proprioceptive sense. It follows that proprioceptive localization should be adequately accounted for in clinical testing and rehabilitation of people with cerebellar damage.     

Quinpirole- and amphetamine-induced hyperdipsia: influence of fluid palatability and behavioral cost

The present study focussed on the development and interaction of reaching and posture in supine position in young infants. The kinematics of goal directed reaches and the concurrent ground reaction forces of the total body centre of pressure (COP) in cranial-caudal and medial-lateral direction were recorded in twelve healthy fullterm infants at 4 and 6 months of age. From eight infants, data were available at both ages. The results indicated that between 4 and 6 months, postural stability during reaching in supine position increased, as the oscillatory COP displacement in the medial-lateral direction decreased significantly with increasing age. Concurrently, reaching performance improved, which was reflected by a decrease in the number of movement units (MU), the length of the displacement-path of the hand and an increase of the length and duration of the first MU. The kinematic data of the reaching movements and the COP data were correlated at both ages, but the nature of the relation changed. At 4 months of age, the number of MU was related to the number of COP oscillations in the cranial-caudal direction, whereas at 6 months the maximum velocity of the hand movement was related to the maximum velocity of COP displacement in cranial-caudal and medial-lateral direction. This change might point to the development of a more subtle control of postural adjustments during reaching movements in supine position.     

X-ray kinematic analysis of forelimb movements during target reaching and food taking in the cat

We have used a three-dimensional X-ray cinematographic approach to investigate the kinematics of the forelimb during target reaching and food taking in five cats. Measurements of the trajectory of the limb during the reaching movement showed that the movement paths of the metacarpophalangeal joint (MCP) and the wrist were sigmoidal with a long nearly linear segment. The elbow followed a bent movement path with maximal inflection in the middle. The path of the humerus had an ascending parabola-like characteristic. The velocity profiles of the MCP and wrist were nearly bell-shaped and skewed to the left, whereas the profiles of the elbow joint were more or less double peaked with the second peak occurring 60-40 ms before object contact. Several different velocity peaks reflecting specific aspects of the task existed when the bell-shaped velocity profiles were divided in their vectorial components. Angular motion of the elbow consisted of a flexion-extension sequence during the reach and a flexion during the subsequent retraction. After an initial flexion during lift-off the wrist was extended. It kept this extended position during orienting towards the food container. During the retraction phase it was further extended. The angle between the wrist axis and the parasagittal plane changed during the movement. It first increased, then decreased during the last 100 ms before the object was reached. During the retraction it increased again to support the object weight against gravity. The position of the wrist was established by radio-ulnar supination and movements of the whole arm around the shoulder joint. We hypothesize that the position of the wrist axis is the controlled variable during protraction and retraction, regardless of whether it is achieved by radio-ulnar supination or by movements around the shoulder.     

Prediction of the body rotation-induced torques on the arm during reaching movements: evidence from a proprioceptively deafferented subject

Reaching for a target while rotating the trunk generates substantial Coriolis and centrifugal torques that push the arm in the opposite direction of the rotations. These torques rarely perturb movement accuracy, suggesting that they are compensated for during the movement. Here we tested whether signals generated during body motion (e.g., vestibular) can be used to predict the torques induced by the body rotation and to modify the motor commands accordingly. We asked a deafferented subject to reach for a memorized visual target in darkness. At the onset of the reaching, the patient was rotated 25° or 40° in the clockwise or the counterclockwise directions. During the rotation, the patient's head remained either fixed in space (Head-Fixed condition) or fixed on the trunk (Head Rotation condition). At the rotation onset, the deafferented patient's hand largely deviated from the mid-sagittal plane in both conditions. The hand deviations were compensated for in the Head Rotation condition only. These results highlight the computational faculty of the brain and show that body rotation-related information can be processed for predicting the consequence of the rotation dynamics on the reaching arm movements.     

Discrepancy between dysmetric centrifugal movements and normometric centripetal movements in psychogenic ataxia

A method to unravel an aberrant motor behaviour in psychogenic ataxia is reported. The kinematic features of fast reaching movements in the vertical plane are described in a patient presenting a psychogenic ataxia. The procedure compared centrifugal and centripetal movements. Path ratios were computed for each phase, as well as the ratios of the paths for centrifugal and centripetal directions. Trajectories of centrifugal phases were erratic but centripetal movements were very regular, whereas both centripetal and centrifugal movements were irregular in patients presenting an organic cerebellar syndrome. A similar incongruity between movements in opposite directions is also shown for a second patient exhibiting psychogenic ataxia. Discrepancies between the centrifugal phase and the centripetal phase of multi-joint reaching movements support the diagnosis of a psychogenic movement disorder.     

A loss of a velocity‐duration trade‐off impairs movement precision in patients with cerebellar degeneration

Current theories discussing the role of the cerebellum have been consistently pointing towards the concept of motor learning. The unavailability of a structure for motor learning able to use information on past errors to change future movements should cause consistent metrical deviations and an inability to correct them; however, it should not boost “motor noise.” However, dysmetria, a loss of endpoint precision and an increase in endpoint variability (“motor noise”) of goal‐directed movements is the central aspect of cerebellar ataxia. Does the prevention of dysmetria or “motor noise” by the healthy cerebellum tell us anything about its normal function? We hypothesize that the healthy cerebellum is able to prevent dysmetria by adjusting movement duration such as to compensate changes in movement velocity. To address this question, we studied fast goal‐directed index finger movements in patients with global cerebellar degeneration and in healthy subjects. We demonstrate that healthy subjects are able to maintain endpoint precision despite continuous fluctuations in movement velocity because they are able to adjust the overall movement duration in a fully compensatory manner (“velocity‐duration trade‐off”). We furthermore provide evidence that this velocity‐duration trade‐off accommodated by the healthy cerebellum is based on a priori information on the future movement velocity. This ability is lost in cerebellar disease. We suggest that the dysmetria observed in cerebellar patients is a direct consequence of the loss of a cerebellum‐based velocity‐duration trade‐off mechanism that continuously fine‐tunes movement durations using information on the expected velocity of the upcoming movement.     

Drug treatment and familiar music aids an attention shift from vision to somatosensation in Parkinson's disease on the reach-to-eat task

Sensory control of the natural skilled movement of reaching for a food target to eat (reach-to-eat) is closely coupled to the successive phases of the movement. Control subjects visually fixate the target from hand movement onset to the point that the digits contact the food, at which point they look away. This relationship between sensory attention and limb movement suggests that whereas limb advance is under visual control, grasping, limb withdrawal, and releasing the food to the mouth is guided by somatosensation. The pattern of sensory control is altered in Parkinson's disease (PD). PD subjects may visually fixate the target for longer durations prior to movement initiation, during the grasp, and during the initial portion of hand withdrawal suggesting that vision compensates for a somatosensory impairment. Because both medication and listening to favorite musical pieces have been reported to normalize some movements in subjects with PD, the present study compared the effect of medication and listening to preferred musical pieces on sensory attention shifts from vision to somatosensation during the reach-to-eat movement. Biometric measures of eye movement and the movement of the reaching limb were collected from PD subjects and aged-matched control subjects in four conditions in their own homes: off medication, off medication with music, on medication, and on medication with music. Unmedicated PD subjects were slower to visually disengage the target after grasping it. Their disengage latency was shortened by both music and medication. Medication and music did not improve other aspects of reaching, including reaching duration and the ratings of the movement elements of limb advance, grasping, and limb withdrawal. The results are discussed in relation to the idea that one way in which medication and music may aid movement in PD by normalizing somatosensory control of forelimb movement thus reducing compensatory visual monitoring.     

The Functional Role of the Cerebellum in Visually Guided Tracking Movement

We propose a new method to provide a functional interpretation of motor commands (i.e., muscle activities) and their relationship to movement kinematics. We evaluated our method by analyzing the motor commands of normal controls and patients with cerebellar disorders for visually guided tracking movement of the wrist joint. Six control subjects and six patients with cerebellar disorders participated in this study. We asked the subjects to perform visually guided smooth tracking movement of the wrist joint with a manipulandum, and recorded the movements of the wrist joint and activities of the four wrist prime movers with surface electrodes. We found a symmetric relationship between the second-order linear equation of motion for the wrist joint and the linear sum of activities of the four wrist prime movers. The symmetric relationship determined a set of parameters to characterize the muscle activities and their similarity to the components of movement kinematics of the wrist joint. We found that muscle activities of the normal controls encoded both the velocity and the position of the moving target, resulting in precise tracking of the target. In contrast, muscle activities of the cerebellar patients were characterized by a severer impairment for velocity control and more dependence on position control, resulting in poor tracking of the smoothly moving target with many step-like awkward movements. Our results suggest that the cerebellum plays an important role in the generation of motor commands for smooth velocity and position control.     

Coupling between reaching movement direction and hand orientation for grasping

In a previous work, we demonstrated that orientation of the hand in the horizontal plane (azimuth) at the time of grasping depends on the direction of the reaching movement in the horizontal plane. Here we report three experiments to further investigate the generality of this coupling. Azimuth of the hand for grasping was studied while subjects were reaching for objects placed at various locations on a horizontal board. Hand movements were recorded with an electromagnetic sensor giving information about hand 3D position and orientation. As expected, hand azimuth for grasping was coupled with movement direction in the central part of the workspace (but reached a limit for rightmost reaching directions). The coupling did not depend on the direction of where the object had to be put after grasping. Various initial positions and azimuths of the hand were compared to the most comfortable initial hand posture. The coupling between hand azimuth and movement direction remained whatever the initial hand azimuth. This demonstrates that reaching movement direction is coupled with azimuth at the time of grasping and not with a rotational hand movement. The coupling between hand azimuth and movement direction subsisted when the initial upper trunk orientation was changed. Thus our results cannot be explained by an invariance of the coupling coded in hand-centered or shoulder-centered coordinates. They rather suggest that the movement is produced in a frame of reference associated with the environment.     

Comparison of cerebellar intention tremor under isotonic and isometric conditions

The characteristics of cerebellar intention tremor were investigated by comparing the properties of tremor following movements about the elbow with that following isometric contractions of biceps and triceps brachii. Cerebellar dysfunction was produced by local, reversible cooling of the dentate and interposed nuclei in three Cebus monkeys. Cerebellar nuclear cooling disrupted isometric contractions to the aimed target and produced oscillations in torque. Whereas the cerebellar tremor that followed movements was regular and had a frequency of 3-5 Hz, the oscillations in the isometric task were irregular and were often of a lower frequency. In addition, cycles of tremor following movements were in phase from trial to trial, while the oscillations that occurred following isometric contractions did not show this phase-relationship. It is concluded that a cerebellar tremor can occur in an isometric situation but that movement about a joint is required for development of a rhythmic 3-5-Hz cerebellar intention tremor.     

Internally driven control of reaching movements: a study on a proprioceptively deafferented subject

We investigated the possibility of controlling reaching movements on the sole basis of central mechanisms, i.e., without peripheral feedback on hand and target positions. A deafferented subject (GL) and control subjects reached with the unseen hand for a straight-ahead target that could be displaced laterally at movement onset. The shifted target was continuously or briefly lit, or not visible. In this latter condition, a beep from either side of subjects' head single-handedly signaled the change in the movement goal, so that movements could only be controlled through an internal representation of the memorised target position. Compared to controls, GL showed quantitatively similar corrections (77% of the target displacement, on an average) and similar reaction times to the target shift (mean = 516 ms), regardless of target visual information. These results highlight a remarkable capacity for controlling reaching movements on the sole basis of internally driven processes. On the other hand, trajectories in double-step trials differed drastically between GL and controls. Controls' trajectories were composed of two segments, the second of which brought the hand directly toward the displaced target. The patient produced three-segment, stair-like trajectories. The first and third segments were mainly in the sagittal plane and the second segment was a vector-image of the lateral target shift. A control experiment showed that GL's trajectories were not the result of a voluntary strategy used to adjust movement trajectory in the absence of peripheral information on hand position. We suggest that GL's trajectories reflect a deficit in interjoint coordination in the absence of proprioception.     

A Japanese girl with leukoencephalopathy with vanishing white matter

A Japanese girl with peculiar leukoencephalopathy was reported. Following normal development until 1 year of age, she showed progressive neurological deterioration with ataxia, epilepsy, pyramidal tract signs and choreic movement. Serial brain computed tomographies (CTs) revealed markedly low density and progressive volume loss in whole white matter. In extensive laboratory investigations, the level of glycine in the urine was elevated. She died at the age of 4 years, and the neuropathological findings were comprised of severe extensive changes in cerebral and cerebellar white matter, such as marked rarefaction or cystic degeneration with axonal loss. The pontine central tegmental tracts were also affected. Neuronal loss was seen in the cerebellar cortex. These features were compatible with leukoencephalopathy with vanishing white matter, which was recently established as a clinical entity. To our knowledge, this is the first report of a non-Caucasian patient with this new type of leukoencephalopathy.     

Impaired temporal prediction and eye-hand coordination in patients with cerebellar lesions

This study investigated the effect of cerebellar lesions on temporal prediction and coordination in eye and hand movements. Nine patients with cerebellar lesions were compared to controls while they made saccades with and without simultaneous pointing movements towards a target that was either temporally predictable or non-predictable. The direction and amplitude of the target step was always predictable. Patients made much more early and late saccades than controls, but an equal amount of visually triggered saccades. This suggests that inappropriate saccades could be suppressed during the preparation of a goal-directed saccade. Hand movement frequency did not differ between both groups. Thus, cerebellar lesions can induce inappropriate saccades more easily than inappropriate hand movements. Controls, but not patients, generated visually triggered saccades of shorter latencies when the target was temporally predictable. Thus, the patients could not use information about target timing to synchronise visually triggered saccades with the target. They could, however, use this information to improve the suppression of inappropriate saccades. Regarding coordination, patients showed impairments in synchronising saccades with hand movements. Nevertheless, hand movements led to an enhancement of anticipatory saccades in patients as in controls. Moreover, hand movements and temporal predictability affected saccadic accuracy in both groups similarly. These results suggest that cerebellar lesions do not generally prevent access to temporal information on the rhythm of a target sequence or the timing of a planned hand movement. More specifically, the cerebellum seems to be crucial for synchronizing saccades with such learned or planned temporal events.     

Evaluations of combined premotor and supplementary motor cortex lesions on a visually guided arm movement

The kinematics of a visually guided, multi-joint arm movement were examined before and after combined bilateral premotor and supplementary motor cortex lesions. Two rhesus monkeys were trained to move a manipulandum from a start zone to one of three equally spaced target zones and then return to the initial start zone. Various features of the movement trajectory including space error, time error, peak velocity and turnaround time were quantified and analyzed before and after the premotor and supplementary motor cortex ablations. Statistical analysis showed no major differences in the trajectories toward or away from the target between the pre- and postlesion state. The major difference following the ablation was increase in the time spent in the target zone, reflecting an increase in time spent in redirecting the trajectory. Normalization of the movement duration revealed a slight delay in the initial part of the movement. These results suggest the premotor and supplementary motor cortex are involved in redirecting the trajectory and/or obtaining the target zone during the execution of a complex movement.     

A neuropathological study of early onset Cockayne syndrome with chromosomal anomaly 47XXX.

We present the clinical and neuropathological findings in a female patient with early onset Cockayne syndrome and a chromosomal anomaly (47XXX). The girl was the only child of healthy, unrelated parents. She was born with a birth weight of 1,930 gm. She had progeroid facial features with bilateral cataracts. A diagnosis of 47XXX was made on the basis of a chromosomal study. Physical shortness became increasingly prominent while her weight remained stationary. Psychomotor retardation was noted, and she could never sit alone. A brain CT scan showed cerebral atrophy and calcification of the basal ganglia. Cultured skin fibroblast exhibited significant sensitivity to the ultraviolet light. She died from a chest infection at the age of 7 years and 4 months. Microscopically, the renal glomeruli showed diffuse sclerotic changes with thick capillary basement membranes. A neuropathological examination revealed a very small brain (295 gm), extensive myelin deficiency, gliosis in the white matter, and calcifications in the basal ganglia, and cerebral and cerebellar cortices. The loss of both Purkinje and granular cells was noticed in the cerebellar cortex. This is the first report of a case with the Cockayne syndrome and 47XXX, and the 47XXX in this patient seems to be coincidental.