Tropical splenomegaly syndrome associated with cytomegalovirus infection.

The tropical splenomegaly syndrome (TSS) is characterized by massive splenomegaly with hypersplenism, moderate hepatomegaly, and lymphocytic infiltration of the hepatic sinusoids. In previous reports this syndrome has been shown to be a consequence of a disordered immunologic response of the host to malarial infection. Treatment with antimalarial drugs has resulted in a decrease in malarial antibody titers and a reduction in splenic size. We report a child who had TSS associated with cytomegalovirus infection rather than malaria. Our results suggest that TSS may be precipitated by a variety of infections producing chronic antigenic stimulation and perhaps by autoantigenic stimulation as well.

Adaptive programming of arm movements.

Adaptations of goal-directed elbow movements of moderate speed, called "continuous" movements and recognized by their single-peaked velocity profiles, were studied for two monkeys that were learning to perform a motor task. The animals were rewarded for what they did, namely, to carry out a step-tracking and holding task by means of discrete elbow movements, but not for how they did it, that is, for any particular mode of movement execution. Yet, both animals increased the use of the programmed, continuous movements when they began to carry out the behavioral task requirements appropriately. Furthermore, continuous movements adapted with increases of peak and of average velocity such that the ratio of these parameters tended to be maintained or decreased. These velocity changes were incorporated into remembered movement programs late in motor learning when the animals approached their best performance proficiencies.

'Error' potentials in limbic cortex (anterior cingulate area 24) of monkeys during motor learning.

Two monkeys were trained to lift a lever with wrist extension in response to a visual cue. The animals were chronically implanted with electrodes for recording transcortical field potentials. Unique 'error' potentials were observed in the anterior cingulate cortical area 24 during a transitional learning-stage when the animals were uncertain about fulfilling the required task appropriately. At that stage (III) about 40-60% of the movements were made appropriately within the required cue-time. Error potentials followed inappropriate lever lifts made with wrist movements that were self-paced and hence non-rewarded, but such potentials did not follow appropriately made, i.e. visually initiated, and rewarded lifts.

How does the limbic system assist motor learning? A limbic comparator hypothesis.

This paper offers a new hypothesis about how the limbic system might assist motor learning. It is proposed that interactions of limbic and sensorimotor-related systems are essential for learning what to do in a motor task (appropriate, relevant behavior) and how to do it best (motor skill). Limbic modulations of sensorimotor-related neural centers are envisaged to result from comparisons in various neural centers of converging inputs from the relevance-sensitive amygdala and from corollary, cortically-modulated recipients of amygdaloid information. Such comparisons of relatively 'raw' limbic inputs and their 'processed', corollary forms could be achieved in a side-loop manner resembling that in the cerebellum. This 'limbic comparator' hypothesis was prompted by studies of motor learning that show how monkeys develop skill only after gaining insight into appropriate, task-related behavior, and that inappropriate behavior during transition into the insightful state produces 'error' signals from the anterior cingulate cortex. Known sites of limbic projections that could serve corollary comparisons are examined with regard to their possible influence on motivation, appropriate, task-related behavior and motor skill. Anatomical and functional tests of convergence and comparison in sensorimotor-related neural centers are suggested in order to stimulate investigations of the limbic comparator hypothesis.

Cerebellar functions in motor control.

How does the cerebellum help to harness the machinery of movement to the intent of the individual, or how is motor "set" implemented? Cerebellar guidance is essential for this purpose, and there is growing agreement that this guidance is based on comparisons of intended and ongoing motor activity. Surprisingly little information exists however, on how guidance is translated into muscle action. Three cerebellar contributions to motor control are considered: Conveyance of set (implemention of motor programs), adaptibility of implementing set under changed conditions (plasticity), and incidental adjustment to circumstances of the moment (ongoing control). Current evidence is examined and found largely negative as to whether these cerebellar functions are carried out through modulation of alpha-gamma coactivation, with the possible exception of the fine control of learned movements.

Movement programming depends on understanding of behavioral requirements.

Use of programmed movements seems to depend on comprehension of the required behavior of which the movements are part. Once this understanding becomes evident by correct behavior, smooth movement take-offs and landings are programmed together. Monkeys were trained to perform a step-tracking task that required accurate self-paced elbow movements of moderate speed. Behavioral aspects of the task, such as correct successive movement directions and timing, were all learned at about the same rates. Use of programmed movements however, increased only after these behavioral requirements had been learned to near the 50% level, i.e., the beginning of behavioral sureness. Movements were programmed as a whole, accelerations together with decelerations, from earliest training onwards.

Motor control. How posture and movements are governed.

This article is a review of the nature of motor control: the abilities and limitations of the body, the principles of doing and learning, how parts of the nervous system interact, and how information is processed to generate the blend of sensory, perceptive, and motor functions that we call motor control. The relation to physical therapy is stressed: PT is regarded as an emerging applied science of motor control, and motor control is regarded as a basic science of physical therapy.

Participation of the principal olivary nucleus in neocerebellar motor control.

A new method for reversible cooling of the inferior olivary nucleus has been used in chronically prepared monkeys. Local olivary cooling depressed discharge of complex spikes of Purkinje cells in contralateral cerebellar cortex. Selective cooling of the principal olive (lateral and dorsal lamellae) produced movement oscillations at about 3-5 Hz of the contralateral arm during cooling in a monkey trained to make prescribed arm movements in the horizontal plane. The effects resemble those of dentate dysfunction. Selective cooling of the dorsal accessory olive and/or the overlying reticular formation, in 3 monkeys, produced during cooling a tendency for postural drift of the contralateral arm and for reduction of its movement amplitudes. These changes tended to vary together according to the degree of cooling. Arm oscillations did not occur. It is concluded that climbing fiber projections from the principal olivary nucleus are essential in the primate for optimal neocerebellar control of arm movements.

Parallel pathways for movement initiation of monkeys.

Participation of the pathway from the cerebellum through "motor" thalamus to motor cortex in movement initiation was tested in three. Cebus monkeys. The animals performed a simple reaction time (RT) task involving prompt elbow flexion or extension in response to an audiovisual "GO!" signal. RTs were not changed by reversible cooling of the arm area of the contralateral ventral lateral (VL) thalamus, that includes rostral VPL. In contrast, cooling the cerebellar dentate nucleus ipsilateral to the operant arm prolonged RTs by about 80 ms, as tested in two of the same monkeys. The results confirm cerebellar participation in prompt generation of well-learned intended arm movements; but they also indicate that although the route through VL-thalamus may be important, it is not essential for initiation of the same movements.

Late muscular responses to arm perturbations persist during supraspinal dysfunctions in monkeys.

This study was conducted to determine which supraspinal structures, if any, are essential for generation of late (M2 and M3) EMG responses to perturbations. EMGs were recorded during active arm movements made by Cebus monkeys trained to resist perturbations applied to a handle and/or during passive movements imposed on sedated or anesthetized animals. EMGs were tested during active movements after ablation of the arm areas of the sensory and caudal motor cortices, during cooling part of the sensorimotor cortex along the central sulcus, and during cooling the arm area in the ventral lateral (VL) thalamus. EMG responses to passive movements were tested after decerebration and decerebellation, after lesions of the motor and/or sensory cortices, during surface cooling the same, and during cooling the VL arm area and the cerebellar dentate nucleus. M1, M2, and M3 were not abolished in any monkey. Decreases in the magnitudes of these responses occurred in some animals, but no reproducible changes in the sizes of M2 and M3 (in comparison to M1) were observed following any procedure. The effects of cortical lesions on M1, M2, and M3 responses to passive movements were found to depend on the level of arousal of the animal. These results demonstrate that M1, M2, and M3 can be produced in the primate spinal cord and brainstem and that the sensorimotor cortex can facilitate these responses.

Increased dependence on visual information for movement control in patients with Parkinson's disease.

Studies were made of visually and non-visually guided movements by patients with Parkinson's disease. The subjects moved a light, horizontal handle using rotation primarily about the elbow. During visually guided trials both handle and target positions were displayed to the subject; during non-visually guided trials only the handle position was displayed. During non-visually guided trials all patients showed a tendency for an overall flexion drift, although there was no change in average movement amplitude. The overall error in position by the end of the non-visually guided trials was greatly in excess of the reported values for passive displacement thresholds in normal subjects. It is suggested that the data indicate an increased dependence on visual information for control of motor activity in Parkinson's patients.

Basal ganglia cooling disables learned arm movements of monkeys in the absence of visual guidance.

Unilateral local cooling in the region of the globus pallidus of Cebus monkeys produced a severe breakdown in the performance of learned flexion-extension elbow movements when animals had no visual information about arm position but not when such information was displayed to them. This result indicates that visual information enables an animal to compensate to a large degree for the motor disorder produced by globus pallidus dysfunction, and it may explain why some previous workers have failed to see motor impairments in monkeys with lesions in the globus pallidus who were observed in their cages.

Precentral unit activity following torque pulse injections into elbow movements.

(1) Precentral neural activity was studied in relation to transient load changes on self-paced elbow movements. Four Cebus monkeys were trained to turn a freely moving handle back and forth between two targets by alternating self-paced elbow flexions and extensions. Torque pulses (of 10 or 100 msec) injected randomly to load or unload the movements stretched or slackened the appropiate prime movers: biceps or triceps. Perturbed movements oscillated at about 5.5 Hz but were completed successfully in about the same time as unperturbed movements. (2) Torque pulses evoked distinct "early" responses with latencies of 20-40 msec in 134 out of 153 precenteral neurons. Oppositely directed torque pulses evoked reciprocal (i.e. increased or decreased) early responses in 61 neurons, and uniform responses in 27 neurons. (3) Early responses were followed by "late" responses with peaks succeeding one another at about 5.5 Hz in 111 neurons, but another 16 exhibited late responses only. (4) Timing of both early and late cortical responses was tightly coupled to peripheral changes. Early responses were timed by the initial torque-induced passive elbow jerk. Timing of late responses was best related to subsequent peak decelerations of accelerations. Intensity of the early but not of all late precentral responses was tightly coupled to peripheral events. (5) Torque pulses that impeded flexions or extensions evoked spinal stretch reflexes in biceps or triceps with EMG latencies of about 15 msec, leading to an acceleration peak about 25 msec later. A second EMG burst followed the first in about 30 msec. The second burst occurred about 20 msec after onset of the early precentral response, which is thought to have caused it, as well as a second acceleration peak that was seen about 60 msec after precentral response (for flexion load pulses). Peaks of late precentral responses were followed by acceleration peaks within about 70 msec. (6) An interaction akin to the spinal stretch reflex is thus revealed between elbow perturbations, early responses of precentral neurons and subsequent elbow movements: discharges of neurons that usually fire in relation to an intended movement can be altered by sudden load changes so that the neurons tend to reduce mismatch between intended and actual movements (cortical load compensation), created by the perturbation. An analagous interaction may also occur with late cortical responses.

Effects of dentate cooling on precentral unit activity following torque pulse injections into elbow movements.

(1) The effects were studied of brief, reversible cooling of the dentate nucleus of two Cebus monkeys on the activity of 69 precentral neurons that were related to self-paced elbow flexions or extensions. Sixty-two neurons were studied when movements were randomly perturbed by transient load changes. (2) During unperturbed movements dentate cooling altered precentral activity and movement parameters in the same direction. Extension movements and extension-related precentral neurons developed oscillations and rhythmical activity at about 4 Hz with increased peak values of acceleration and discharge intensity. Flexion peak accelerations and dynamic properties of flexion-related precentral neurons decreased. (3) Dentate cooling had no major effects on the "early" precentral responses to torque pulses and on the initial rapid movement adjustment. (4) Dentate cooling decreased intensity of "late" precentral responses and slowed their frequency together with associated movement oscillations from 5-6 Hz to 3-4 Hz. EMG bursts of biceps and triceps were prolonged accordingly. (5) It is concluded that the tightly coupled interaction between precentral motor cortex and the evolving movement was independent of dentate function in the early stage of the cortical load compensation. The dentate nucleus was involved, however, in adjusting intensity and frequency of subsequent late precentral responses and of movement oscillations.