On-beam synchrony in the cerebellum as the mechanism for the timing and coordination of movement.

In trained reaching rats, we recorded simple spikes of pairs of Purkinje cells that, with respect to each other, were either aligned on a beam of shared parallel fibers or instead were located off beam. Rates of simple spike firing in both on-beam and off-beam Purkinje cell pairs commonly showed great variety in depth of modulation during reaching behavior. But with respect to timing, on-beam Purkinje cell pairs had simple spikes that were tightly time-locked to each other (either delayed or simultaneous) and to movement, despite the variability in rate. By contrast, off-beam Purkinje cell pairs had simple spikes that were not time-locked to each other, neither delayed nor simultaneous. We discuss the implications of these observations for the cerebellar role in timing and coordinating movement.

Signal-to-noise ratio improvement in multiple electrode recording.

Recordings of spike trains made with microwires or silicon electrodes include more noise from various sources that contaminate the observed spike shapes compared with recordings using sharp microelectrodes. This is a particularly serious problem if spike shape sorting is required to separate the several trains that might be observed on a particular electrode. However, if recordings are made with an array of such electrodes, there are several mathematical methods to improve the effective signal (spikes) to noise ratio, thus considerably reducing inaccuracy in spike detection and shape sorting. We compare the theoretical basis of three such methods and evaluate their performance with simulated and real data.

Patellar ligament reconstruction using allograft patellar ligament: a case report.

This report describes a method of patellar ligament reconstruction. Our patient sustained a rupture of the patellar ligament and had reconstruction with allograft patellar ligament after failed primary repair. At the 2-year follow-up, his range of motion was 0 degrees to 110 degrees and he was able to return to unrestricted standing work.

No clock signal in the discharge of neurons in the deep cerebellar nuclei.

We examined the spike activity of deep cerebellar nuclear cells recorded from awake, behaving monkeys to determine if there was a tendency for periodic discharge at or near 10 Hz. Data were obtained from four Rhesus monkeys trained to perform either targeted flexions and extensions of the wrist in relation to a visual cue (2 monkeys) or instrumented digit movements and natural reaches (2 monkeys). We determined the interspike intervals of 274 isolated cells. We looked for periodicity by autocorrelating the interval data and Fourier transforming the resulting autocorrelation function. The autocorrelograms and the Fourier transforms failed to reveal periodicity at or near 10 Hz for any cell. This lack of oscillatory discharge in deep nuclear cells of the cerebellum is consistent with our previously reported results that the complex spike of the Purkinje cell is aperiodic. Our failure to observe a clocklike timing signal in awake, behaving animals in either the Purkinje cell complex spike or the deep nuclear cell discharge argues against a popular idea that the inferior olive may act through the cerebellum as a motor clock.

Throwing while looking through prisms. I. Focal olivocerebellar lesions impair adaptation.

Normal human subjects and patients with lesions of the olivocerebellar system threw balls of clay at a visual target while wearing wedge prism spectacles. Normal subjects initially threw in the direction of prism-bent gaze, but with repeated throws adapted to hit the target. Patients with generalized cerebellar atrophy, inferior olive hypertrophy, or focal infarcts in the distribution of the posterior inferior cerebellar artery, in the ipsilateral inferior peduncle, in the contralateral basal pons or in the ipsilateral middle cerebellar peduncle had impaired or absent prism adaptation. Patients with infarcts in the distribution of the posterior inferior cerebellar artery usually had impaired or absent adaptation but little or no ataxia. By contrast, patients with damage in the distribution of the superior cerebellar artery or in cerebellar thalamus usually had ataxia but preserved adaptation. These results implicate climbing fibres from the contralateral inferior olive via the ipsilateral inferior cerebellar peduncle, mossy fibres from the contralateral pontocerebellar nuclei via the ipsilateral middle cerebellar peduncle, and posterior inferior cerebellar artery territory cortex as being critical for this adaptation. The dentatothalamic projection and the superior cerebellar artery territory cortex are not necessary for this adaptation.

Throwing while looking through prisms. II. Specificity and storage of multiple gaze-throw calibrations.

Human subjects threw balls of clay at a visual target while looking through wedge prism spectacles. In studies of short-term adjustment, subjects threw in the direction of their prism-bent gaze, missing the target to that side. Within 10-30 throws, they gradually adapted with a wider gaze-throw angle and hit the target. Immediately after removal of the prisms the wide gaze-throw angle persisted and throws missed the target to the opposite side, the so-called 'negative after effect'. Repeated throws were required to adapt back to the normal gaze-throw angle and hit the target. The adaptation was specific both to the body parts trained and the type of throw trained: training with the right hand did not generalize to throwing with the left; overhand training seldom generalized to underhand throwing. In a study of long-term adjustment, two subjects threw with the same hand (right) and the same type of throw (overhand) alternately, with and without prisms, over a period of 6 weeks. They gradually learned to hit the target on the first throw, with and without prisms. The two gaze-throw calibrations (prism and no-prism) were retained for > 27 months. The long-term adjustment was shown to consist of a coordinated relationship of eye-in-head, head-on-trunk and trunk-on-arm angles.

Cerebellar ataxia: abnormal control of interaction torques across multiple joints.

1. We studied seven subjects with cerebellar lesions and seven control subjects as they made reaching movements in the sagittal plane to a target directly in front of them. Reaches were made under three different conditions: 1) "slow-accurate," 2) "fast-accurate," and 3) "fast as possible." All subjects were videotaped moving in a sagittal plane with markers on the index finger, wrist, elbow, and shoulder. Marker positions were digitized and then used to calculate joint angles. For each of the shoulder, elbow and wrist joints, inverse dynamics equations based on a three-segment limb model were used to estimate the net torque (sum of components) and each of the component torques. The component torques consisted of the torque due to gravity, the dynamic interaction torques induced passively by the movement of the adjacent joint, and the torque produced by the muscles and passive tissue elements (sometimes called "residual" torque). 2. A kinematic analysis of the movement trajectory and the change in joint angles showed that the reaches of subjects with cerebellar lesions were abnormal compared with reaches of control subjects. In both the slow-accurate and fast-accurate conditions the cerebellar subjects made abnormally curved wrist paths; the curvature was greater in the slow-accurate condition. During the slow-accurate condition, cerebellar subjects showed target undershoot and tended to move one joint at a time (decomposition). During the fast-accurate reaches, the cerebellar subjects showed target overshoot. Additionally, in the fast-accurate condition, cerebellar subjects moved the joints at abnormal rates relative to one another, but the movements were less decomposed. Only three subjects were tested in the fast as possible condition; this condition was analyzed only to determine maximal reaching speeds of subjects with cerebellar lesions. Cerebellar subjects moved more slowly than controls in all three conditions. 3. A kinetic analysis of torques generated at each joint during the slow-accurate reaches and the fast-accurate reaches revealed that subjects with cerebellar lesions produced very different torque profiles compared with control subjects. In the slow-accurate condition, the cerebellar subjects produced abnormal elbow muscle torques that prevented the normal elbow extension early in the reach. In the fast-accurate condition, the cerebellar subjects produced inappropriate levels of shoulder muscle torque and also produced elbow muscle torques that did not very appropriately with the dynamic interaction torques that occurred at the elbow. Lack of appropriate muscle torque resulted in excessive contributions of the dynamic interaction torque during the fast-accurate reaches. 4. The inability to produce muscle torques that predict, accommodate, and compensate for the dynamic interaction torques appears to be an important cause of the classic kinematic deficits shown by cerebellar subjects during attempted reaching. These kinematic deficits include incoordination of the shoulder and the elbow joints, a curved trajectory, and overshoot. In the fast-accurate condition, cerebellar subjects often made inappropriate muscle torques relative to the dynamic interaction torques. Because of this, interaction torques often determined the pattern of incoordination of the elbow and shoulder that produced the curved trajectory and target overshoot. In the slow-accurate condition, we reason that the cerebellar subjects may use a decomposition strategy so as to simplify the movement and not have to control both joints simultaneously. From these results, we suggest that a major role of the cerebellum is in generating muscle torques at a joint that will predict the interaction torques being generated by other moving joints and compensate for them as they occur.

Nonclock behavior of inferior olive neurons: interspike interval of Purkinje cell complex spike discharge in the awake behaving monkey is random.

1. Complex spikes of cerebellar Purkinje cells recorded from awake, behaving monkeys were studied to determine the extent to which their discharge could be quantified as periodic. Three Rhesus monkeys were trained to perform up to five different tasks involving rotation of the wrist in relation to a visual cue. Complex spike activity was recorded during task performance and intertrial time. Interspike intervals were determined from the discharge of each of 89 Purkinje cells located throughout lobules IV, V, and VI. Autocorrelation and Fourier transform of the autocorrelation function were performed on the data. In addition, the activity from one cell was transformed so that the discharge occurred on the beat of a 10-Hz clock, and in a further transformation, on the beat of a noisy 10-Hz clock. These transformed data were then analyzed as described above. 2. Fourier transform of the autocorrelogram function of the data that had been transformed to a 10-Hz clock, and that of the noisy 10-Hz clock, both showed a prominent peak at 10 Hz. However, the autocorrelograms and the Fourier transforms of the autocorrelogram functions failed to reveal a prominent periodicity for the actual discharge of any of cells, at any frequency up to 100 Hz: the discharge appeared random with respect to the interspike interval. The discharge was not random with respect to behavior. Complex spike activity was commonly time locked to the start of wrist movement. We examined this discharge to see whether oscillatory discharge could be seen after alignment of the data on the start of wrist movement, or after alignment of the data on the complex spike occurring peri-start of wrist movement. No oscillation was seen for either alignment. 3. The inferior olive, which sends its climbing fibers to the cerebellum, has been implicated in such different activities as 1) pathological tremor of the soft palate, 2) physiological tremor, 3) the normal initiation of all bodily movement, and 4) motor learning. Previous work in pharmacologically or surgically treated animals has shown that, under some conditions, the discharge of these neurons is periodic and synchronous. This firing pattern has been interpreted to support a role in the first two activities. But measurements reported here in the awake monkey show just the opposite: the discharge is aperiodic to the extent of being random. As such, the inferior olive cannot be a "motor clock" in the general role that has been proposed.(ABSTRACT TRUNCATED AT 400 WORDS)

Preserved simple and impaired compound movement after infarction in the territory of the superior cerebellar artery.

A patient with an infarct in the distribution of the right superior cerebellar artery was studied with regard to his ability to make simple movements (visually triggered, self-terminated ballistic wrist movements), and compound movements (reaching to a visual target and precision pinch of a seen object). Movements on the right side of the body alone were affected. Control movements were made by the normal left upper extremity. Wrist movement on the right side was normal in reaction time, direction, peak velocity, and end-point position control as compared to the left. By contrast, both reaching and pinching movements on the right were impaired. Reaching movements showed marked decomposition of the compound elbow-shoulder movement into seriatim simple movements made alternately at elbow and shoulder. Pinching movements were not made, and instead winkling movements (a movement of index alone) were substituted. These results are compared to similar results of controlled inactivation of the cerebellar dentate nucleus in monkeys. We conclude that one function of the cerebellum may be to combine elements in the movement repertoires of downstream movement generators. When that ability is lost, a strategy may be voluntarily adopted of using the preserved simple movements in place of the impaired compound movements.

The cerebellum and the adaptive coordination of movement.

Based on a review of cerebellar anatomy, neural discharge in relation to behavior, and focal ablation syndromes, we propose a model of cerebellar function that we believe is both comprehensive as to the available information (at these levels) and unique in several respects. The unique features are the inclusion of new information on (a) cerebellar output--its replicative representation of body maps in each of the deep nuclei, each coding a different type and context of movement, and each appearing to control movement of multiple body parts more than of single body parts; and (b) the newly assessed long length of the parallel fiber. The parallel fiber, by virtue of its connection through Purkinje cells to the deep nuclei, appears optimally designed to combine the actions at several joints and to link the modes of adjacent nuclei into more complex coordinated acts. We review the old question of whether the cerebellum is responsible for the coordination of body parts as opposed to the tuning of downstream executive centers, and conclude that it is both, through mechanisms that have been described in the cerebellar cortex. We argue that such a mechanism would require an adaptive capacity, and support the evidence and interpretation that it has one. We point out that many parts of the motor system may be involved in different types of motor learning for different purposes, and that the presence of the many does not exclude an existence of the one in the cerebellar cortex. The adaptive role of the cerebellar cortex would appear to be specialized for combining simpler elements of movement into more complex synergies, and also in enabling simple, stereotyped reflex apparatus to respond differently, specifically, and appropriately under different task conditions. Speed of learning and magnitude of memory for both novel synergies and task-specific performance modifications are other attributes of the cerebellar cortex.