Kinematic analysis of manual tracking in monkeys: characterization of movement intermittencies during a circular tracking task.

Segmentation of the velocity profiles into the submovements has been observed in reaching and tracking limb movements and even in isometric tasks. Submovements have been implicated in both feed-forward and feedback control. In this study, submovements were analyzed during manual tracking in the nonhuman primate with the focus on the amplitude-duration scaling of submovements and the error signals involved in their control. The task consisted of the interception and visually guided pursuit of a target moving in a circle. The submovements were quantified based on their duration and amplitude in the speed profile. Control experiments using passive movements demonstrated that these intermittencies were not instrumentation artifacts. Submovements were prominent in both the interception and tracking phases and their amplitude scaled linearly with duration. The scaling factors increased with tracking speed at the same rate for both interception and pursuit. A cross-correlation analysis between a variety of error signals and the speed profile revealed that direction and speed errors were temporally coupled to the submovements. The cross-correlation profiles suggest that submovements are initiated when speed error reaches a certain limit and when direction error is minimized. The scaling results show that in monkeys submovements characterize both the interception and pursuit portions of the task and that these submovements have similar scaling properties consistent with 1) the concept of stereotypy and 2) adding constant acceleration/force at a specific tracking speed. The correlation results show involvement of speed and direction error signals in controlling the submovements.

Motor skill learning in patients with cerebellar degeneration.

To explore the role of the cerebellum in learning a complex motor task, we studied nineteen patients with cerebellar degeneration and sixteen healthy subjects who attempted to improve their performance in generating a trajectory connecting five via points on a data tablet. Multijoint arm movements were performed at a constant total movement time, and spatial error was measured. Subjects performed 100 trials at a movement time of 3.5 s (slow movements), and another 100 trials at maximum speed (fast movements). With slow movements, patients and normal subjects reduced the error over trials to the same extent, but in patients, the rate of improvement was slightly slower. With fast movements, patients showed less improvement than normal subjects. When tested 24 h later, patients demonstrated significant retention of acquired skill and tended to improve more rapidly when performing both slow and fast movements than during the first session. We conclude that patients with cerebellar degeneration can exhibit almost normal performance in skill learning with slow movements, but with fast movements, their performance improves to a lesser extent. The problem may be difficulty in the refinement of motor execution, which is more of a requirement for fast movements than for slow ones.

The intermediate cerebellum may function as a wave-variable processor.

A newly developed model suggests that the intermediate cerebellum and spinal cord gray matter may contribute to movement control by processing control signals as wave variables. Within specialized communication systems, wave variables are combinations of forward and return signals that ensure stable exchange between two sites despite transmission delays. The composition of signals transmitted in the ventral spinocerebellar tract appears to be consistent with that of a wave variable, and computer simulations of the model yield signals similar to those observed in the monkey interpositus nucleus. Wave-variable communication may enable the animal motor system to maintain stable, high-performance feedback control in the presence of potentially destabilizing signal transmission delays.

Proton magnetic resonance spectroscopic imaging in patients with cerebellar degeneration.

Using proton magnetic resonance spectroscopic imaging, we studied the cerebellum of 9 patients with cerebellar degeneration and of 9 age-matched normal control subjects. This technique permits the simultaneous measurement of N-acetylaspartate, choline-containing compounds, creatine/phosphocreatine, and lactate signal intensities from four 15-mm slices divided into 0.84-ml single-volume elements. Because patients with cerebellar degeneration often show substantial atrophy on magnetic resonance imaging (MRI), we specifically chose to analyze the spectroscopic signals only from tissue that did not have an atrophic appearance on the MRI. The spectroscopic findings showed a significant reduction of N-acetylaspartate in all parts of the cerebellum, a significant correlation with MRI scores of cerebellar atrophy, and a significant correlation with clinical rating scores of cerebellar disturbance. Our method of analysis suggests the presence of a neurodegenerative process in cerebellar areas that do not appear to be atrophic on the MRI. Some limitations of proton magnetic resonance spectroscopic imaging in the present study were related to the partial field inhomogeneity characteristics of the posterior fossa, the anatomical location of the cerebellum, and the particularly severe cerebellar atrophy in some of the patients.

An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan.

OBJECTIVE: To determine whether L-5-hydroxytryptophan (L-5-HTP) associated with eosinophiliamyalgia syndrome (EMS) like illness contains impurities in a fashion similar to that described in L-tryptophan associated with EMS. METHODS: Members of a family who became ill after exposure to L-5-HTP were evaluated at the National Institutes of Health. Data from patients with extended exposure to L-5-HTP were also examined. Samples of L-5-HTP were examined using high performance liquid chromatography. RESULTS: One member of the family had EMS, and 2 others had eosinophilia. No patient in the other group reviewed developed the syndrome, although 2 patients developed eosinophilia. The L-5-HTP used by the family contained an impurity not present in samples from the other patient group. After replacement with L-5-HTP not containing this impurity, eosinophilia in 2 family members resolved. CONCLUSION: Some L-5-HTP contains impurities that may be related to L-5-HTP associated EMS.

Deficit in classical conditioning in patients with cerebellar degeneration.

There is evidence from animal experiments that the cerebellum and its associated brainstem circuitry are involved in the acquisition of the conditioned response. In order to obtain evidence for their involvement in humans, we studied classical delay conditioning, using the eye-blink conditioned response, in five patients with pure cerebellar cortical atrophy and seven patients with olivopontocerebellar atrophy. The results were compared with those obtained in a group of neurologically healthy volunteers matched with the patients for age and sex. The two groups of patients had similar abnormalities in the acquisition of the conditioned response and produced fewer conditioned responses than in the control subjects in any given block of trials. Many of the patients' conditioned responses were inappropriately timed with respect to the conditioned stimulus. These results support the role of the cerebellum in the expression and timing of the conditioned response.

Physiologic studies of dysmetria in patients with cerebellar deficits.

A feature of cerebellar ataxia is dysmetria, which is characterized by inaccurate movements. Studies of rapid movements at a single joint show prolonged acceleration phases and prolonged initial bursts of EMG activity in the agonist muscle. These two features correlate with each other, suggesting that the prolongation of the neural signal is responsible for the kinematic abnormality. This explains a tendency to hypermetria. Studies of multijoint movements show abnormalities in relative timing of the different joints. During locomotion, knee and ankle motions can be delayed differentially with respect to the gait cycle. Subjects attempting straight-line movements with the arm have systematic deviations that reflect incoordination of the shoulder and elbow with respect to each other. A possible explanation of dysmetria is a failure of sufficient force generation within the necessary time to accomplish a coordinated movement. Another possible explanation is that the cerebellum is responsible for timing of brain functions.

A limit cycle mathematical model of the REM sleep oscillator system.

A limit cycle mathematical model of the rapid-eye-movement (REM) sleep oscillator system has been developed from a structural model of interaction of populations of REM-on and REM-off neurons. The marked differences in latency, amplitude, and duration of the first REM sleep period seen with circadian variation and depressive pathology are modeled by beginning the REM oscillation at different initial points relative to the final position in the limit cycle. Beginning from a point that is graphically interior to the limit cycle produces a long-latency, short-duration, and less intense first REM period. Beginning from a point graphically exterior to the limit cycle produces a short-latency, long-duration, and more intense first REM period. In the model the determinant of whether the oscillation begins exterior or interior to the limit cycle is the time course of decay of the REM-off population discharge activity at sleep onset. When this time course is made to depend on circadian phase, the model produces a very close match to the empirically observed large shifts between the first and second REM periods in duration (often a 50% change) and intensity and also closely mimics the empirically observed shifts in REM latency as human sleep begins at different circadian phases. Although this variation in limit cycle entry accounts for the major changes in REM sleep over the night, the model also postulates a continuous but small circadian variation (of the order of +/- 5% change in REM parameters) acting throughout the course of a night's sleep. Because the model is derived from actual physiological data, rather than being a purely ad hoc or phenomenological construct, it offers the possibility of direct tests of its postulates through neurobiological studies in animals, by circadian phase-related manipulations of the sleep cycle, and through perturbations of the system in humans by the use of drugs. Indeed, an explicit phase-response curve of the system to cholinergic agonists has been developed; this will permit experimental tests of the model in both animals and humans.

Further discussion of a model of the REM sleep oscillator.

The limit cycle feature and the grounding of our model in physiology are endorsed by Daan and Beersma [Am. J. Physiol. 251 (Regulatory Integrative Comp. Physiol. 20): R1030-R1032, 1986.] as well as the fundamental postulate of the model that the latency, duration, and intensity of the first rapid-eye-movement (REM) period depends on whether the limit cycle is entered from an internal or external trajectory, and the fact that this trajectory is determined by circadian modulation of conditions at sleep onset. We describe our reasons for preferring a more explicit formulation of the sleep onset conditions than provided in our earlier "Karma" version of this model and provide additional details of how the control of the REM-off population decline is modeled. Additional empirical evidence is cited for the continuous circadian modulation of REM cycle parameters. We emphasize that, compared with the original simple model, the present version of the model adds only one additional "free" initial condition parameter (circadian phase) that is used to model normal sleep begun at different circadian phases and the resultant variations in REM latency, duration, intensity, and period length. We present specific predictions of the model and new supporting empirical data.