Visuomotor control abnormalities in patients with unilateral parkinsonism.

Visuomotor performance is known to be disturbed in patients who have advanced Parkinson's disease (PD). The degree of impairment in the early stages of PD was investigated in both the symptomatic and asymptomatic hand of patients with unilateral disease. We examined the visuomotor performance of 10 early unilateral parkinsonian patients and 15 control subjects by using several tracing and tracking tasks that were performed with unseen hands, in which feedback was given through a screen cursor. Significant impairment in control of movement direction was found in tracing of screen paths but not in tracking. Significant slowing of movement was found in target tracking, whereas tracing velocity was normal. Although all patients were judged by standard clinical criteria to be unilaterally affected, visuomotor functions were found to be impaired equally in both hands. Visuomotor control of movement direction and movement velocity is performed independently. Performance along both control dimensions is impaired in the mild stages of parkinsonism, even before the appearance of motor symptoms.

Two-dimensional tracing and tracking in patients with Parkinson's disease.

We investigated the execution of two-dimensional, visually guided hand movements in patients with Parkinson's disease (PD) and in control subjects. Testing involved moving an unseen handle along a straight line or a sinusoidal path over a horizontally placed digitizing tablet. The path was displayed on a computer screen together with a pointer that represented the handle's location. The size of all video displays corresponded, with a 1:1 ratio, to the actual movements. We used the following tests. (1) Tracing, in which each subject was asked to move the pointer over the entire path, from left to right, with no speed requirements. (2) Tracking along a displayed path: a small circle moved along the path at a speed of 4, 7, or 10 mm/sec. The subject was asked to maintain the pointer inside the circle throughout its movement. When missed, the circle stopped moving until the pointer was again brought inside it. (3) Tracking along an unseen path: same as (2), except that the path was not displayed. Analysis of movement accuracy and of movement kinematics revealed that the patient's ability to control the direction of hand movement was impaired and that this impairment was evident in tracing as well as in tracking, was greater for sinusoidal than for straight-movement paths, and was independent of movement speed.

Trajectory-selective neuronal activity in the motor cortex of rhesus monkeys (Macaca mulatta).

Neuronal activity recorded in the primate motor cortex reflected movement parameters in addition to the distance and direction of a target. These neurons may reflect the selection, from memory, of a detailed movement trajectory to be executed in response to visuospatial instructions.

Improvement in cognition associated with novel antipsychotic drugs: a direct drug effect or reduction of EPS?

BACKGROUND: Administration of novel, versus classic, antipsychotic agents to patients suffering from psychosis is associated both with moderately better scores on cognitive tests, and with fewer extrapyramidal symptoms (EPS). Because improved motor functioning may enable better performance on some components of cognitive test batteries, and because the advantages of the novel antipsychotics on cognitive performance are not very large, it is sometimes difficult to discern if improvement in a given cognitive task is due to a direct effect of the novel antipsychotic drug, or is secondary to the novel drug's decreased propensity to induce EPS. In an attempt to distinguish between these two possibilities, the present study examined the ability of patients suffering from schizophrenia receiving classic, versus novel antipsychotics, to perform a computerized visuo-motor test (VMT). VMT assesses planning capabilities, attention and executive functions known to be impaired in schizophrenia, which are suggested to be affected by novel antipsychotics. METHODS: Seventy-six patients suffering from schizophrenia or schizophreniform disorder, receiving haloperidol (23 patients, mean dose 10.01+/-6.1mg/day), olanzapine (26 patients, mean dose 10.56 +/- 4.9 mg/day) or risperidone (27 patients, mean dose 4.35 +/- 1.7 mg/day) were assessed for EPS using the parkinsonian subscale of the Extrapyramidal Symptom Rating Subscale (ESRS), and with the VMT. RESULTS: Cognitive functioning as measured by the VMT was better for patients receiving risperidone or olanzapine, compared with those receiving haloperidol (F=6.636, df=2,67, P=0. 002), while the patients receiving haloperidol or risperidone suffered from more severe EPS compared with the patients receiving olanzapine (F=3.996, df=2,71, P=0.023). DISCUSSION: Although the patients receiving risperidone suffered from EPS similar in severity to the EPS of the patients receiving haloperidol, their performance on a task involving visuo-motor and attentional skills was similar to that of the patients receiving olanzapine. This finding implies that there is a dissociation between the antipsychotic drug's ability to affect cognitive functioning, and EPS. This dissociation indirectly suggests that the advantages offered by novel antipsychotics on cognitive performance are a direct effect, rather than being entirely mediated by improved movement abilities.

Reduction of NMDA-induced Ca2+ transients by a mu-opioid receptor agonist in dorsal horn neurons.

The effect of DAMGO, a mu-opioid receptor agonist, on intracellular Ca2+ transients evoked by the application of NMDA, was studied in freshly dissociated neurons from the superficial dorsal horn in the spinal cord of young rats. DAMGO (5-10 microns) reduced the amplitude of the Ca2+ transients measured with Fura-2 to 58 +/- 17% of the controls in 41% of the neurons tested. The effect of DAMGO was dose dependent and reversible. The reduction of NMDA-induced Ca2+ transients by DAMGO was prevented by application of the opioid antagonists naloxone (0.1-5 microM) and CTAP (0.2-2 microM). DAMGO also reduced Ca2+ transients induced by high K+ in 29% of the neurons. These data suggest that mu-receptor activation regulates NMDA-induced Ca2+ transients in a complex manner, by reducing both a depolarization-induced component and the NMDA-channel component of this Ca2+ signal.

Auditory- and movement-related neural activity interact in the pulvinar of the behaving rhesus monkey.

We recorded the activity of 101 pulvinar nucleus neurons in a rhesus monkey performing an auditory discrimination task. The monkey was trained to push a lever to the left after hearing a noise burst and to the right after hearing a tone. When the stimulus was presented every 3 s the auditory evoked potentials (AEPs) habituated very rapidly to about 10% of initial height. With a stimulation rate of 1 every 15 s, however, the AEPs maintained full amplitude. A movement-related increase in firing rate was recorded in 81 units (80%) and could usually be detected 100-200 ms before onset of arm EMG. A stimulus-related firing was detected in 70 units (69%). Most of the stimulus-driven units (65/70) were also movement-driven. No responses correlated to the movement or to the sound stimuli were seen during passive conditions, i.e. when the monkey was not engaged in task performance. The occurrence of both stimulus- and movement-related activity in single pulvinar units suggests sensory-motor interaction possibly related to the decision to perform a certain movement.

The response of single units in the auditory cortex of rhesus monkeys to predicted and to unpredicted sound stimuli.

Rhesus monkeys were trained to predict the nature of short auditory signals of two different types, to which they responded differentially. Prediction was based on visual signals that preceded the auditory ones. The monkey's use of the visual signals as predictors was assessed through two behavioural criteria. (1) performance in trials in which the visual signals was followed by the correct auditory signal (true conditioning) vs performance in trials in which the visual signal was followed by the wrong auditory signal (false conditioning). (2) Reaction time in trials with different types of conditioning. The response of single auditory cortex units to correctly and to incorrectly predicted auditory signals was recorded. The unconditioned response of every unit to each type of auditory stimulus was also obtained. Of 92 units that were analysed in detail, the response of about half was affected by the predictability of the stimulus. Units were affected in two different ways. One involved facilitation of the response to correctly predicted signals and inhibition of the response to incorrectly predicted signals. The other involved facilitation of the response to incorrectly predicted signals and base line response to correctly predicted signals. These findings were discussed in terms of neural mechanisms that relate to prediction.

Evoked unit activity in auditory cortex of monkeys performing a selective attention task.

Single-unit responses were recorded from the auditory cortex of rhesus monkeys performing a selective atteintion task which used combined light and sound stimuli. The animals were first trained to push a lever to the left for a noise burst and to the right for a tone burst, and then trained to push left for a left light and right for a right light. Subsequently, one of the four possible light and sound stimulus combinations (Noise + Left Light, Noise + Right Light, Tone + Left Light, Tone + Right Light) was randomly presented on each trial. In blocks of 100 trials only one part of the combined stimulus (either the light or the sound) determined the direction of lever push that would be reinforced. Responses of single units to identical sound stimuli were compared for blocks in which sound was the relevant cue and blocks in which light was the relevant cue. Typically, differences were in response strength without alteration of response pattern. Even the earliest response components (15-20 msec latency) could show changes. Two-thirds of the response comparisons showed differences in strength depending upon whether sound or light was the relevant cue, with about as many responses stronger for light relevant as for sound relevant. Independent of which modality was relevant, unit responses for trials in which both parts of the combined light and sound stimulus indicated the same direction of lever push were generally stronger than unit responses for trials in which the two parts of the combined stimulus signalled opposite directions of lever pushes.

Deprenyl monotherapy improves visuo-motor control in early parkinsonism.

Deprenyl is a potent MAO-B inhibitor which is commonly prescribed for treatment of parkinsonism. Despite prevalent use its effects on the symptoms and course of Parkinson's disease (PD) are still debated. The present study was therefore undertaken in order to measure quantitatively changes in visuo-motor control (VMC), consequent to deprenyl monotherapy in early PD. Previous work from our laboratory has shown typical VMC deterioration in PD patients, that correlates with disease severity. Thus, measurements of such changes provides a sensitive tool with which the symptomatic effects of drug treatment can be assessed quantitatively. Fourteen newly diagnosed, PD patients with light symptoms were studied. The VMC of all patients was tested after the first neurological examination, before drug treatment commenced. A second test was done after 30 days of treatment with deprenyl at a dose of 2.5 mg/day. Following this test, dosage was increased to 10 mg/day and a third VMC test was given after 30 more days of treatment. Our results show significant improvement in VMC functions following 30 days of 2.5 mg/day treatment and a continuing improvement after the next 30 days of 10 mg/day treatment. This improvement pertains mainly to directional control of self initiated movements and is smaller for movements that are guided externally. We conclude that deprenyl monotherapy has a clear symptomatic beneficial effect for patients with early PD.

The effect of deprenyl treatment on directional and velocity control of arm movement in patients with early stages of Parkinson's disease.

Visual motor control (VMC) of arm movements is disturbed in patients with Parkinson's disease. The effect of antiparkinsonian medications on VMC is unknown. To assess the effect of deprenyl, a monoamine oxidase type B inhibitor, on VMC in the early stages of parkinsonism. Fourteen recently diagnosed, unmedicated patients with primary degenerative parkinsonism, mean age 61.9 +/- 2.8 years, were assessed by a computerized VMC system for tracking and tracing on a sine wave, circle, and square. Score was given for total time of test performance, directional error, arm velocity, and number of interruptions in tracking. All patients performed the first VMC test at baseline, prior to any antiparkinsonian treatment. The second test was performed after a month of treatment with 2.5 mg/d of deprenyl, and the third test was done after an additional month of treatment with 10 mg/d of deprenyl. Results were compared with 15 healthy volunteers with a mean age of 63.1 +/- 1.2 years. Parkinsonian patients performed significantly poorer on the VMC when compared to controls. Tracing was more affected than tracking. Tracing total time was almost twice as long as for controls (p < .0005). Treatment with 2.5 mg/d and 10 mg/d of deprenyl improved performance significantly (p < .05 and p < .005, respectively). Velocity of arm movement was not affected by deprenyl treatment in either dose. Directional control (tracing), severely disturbed in the parkinsonian group, improved back to the performance of healthy controls after 10 mg/d of deprenyl. In recently diagnosed parkinsonian patients internally guided VMC tasks were disturbed more than externally guided ones. Deprenyl treatment selectively improved directional control of arm movement in a dose related manner.

L-DOPA improves visuo-motor coordination in stable Parkinson's disease patients.

The visuo-motor coordination of 26 stable, treated, Parkinson's disease (PD) patients with average Hoehn and Yahr rating of 1.75+/-0.6, was assessed by use of several tracing and tracking tests before and 30min after ingestion of the mid-day levodopa (L-DOPA) dose. Significant improvement was found in all aspects of visuo-motor coordination 30min after drug intake. This included the ability to control the direction and velocity of hand-movement, and the capacity to persist in tracking. A subgroup of 12 patients was tested 30min and 1h after L-DOPA intake. A continuing (but small) improvement in directional and velocity control could still be seen an hour after drug intake, while tracking persistence remained unchanged with respect to the preceding test. We conclude that changes in executional capabilities can be documented in "stable" PD patients, consequent to L-DOPA intake, when high-level skills, such as visuo-motor coordination, are tested.

Stroke rehabilitation. Three exercise therapy approaches.

The purpose of this study was to compare the therapeutic efficacy of three exercise therapy approaches. Three groups of adult stroke patients (N = 131) participated in the study. The first group received conventional treatment that consisted of traditional exercises and functional activities. The treatment of the second group was based on proprioceptive neuromuscular facilitation techniques. The third group was treated using the Bobath approach. The improvement of each patient was evaluated after six weeks of treatment in terms of functional gains in activities of daily living as measured using the Barthel index, changes in the muscle tone of the involved limbs as measured using a five-point ordinal scale, changes in the isolated motor control of the ankle and wrist as measured by tests of muscle strength and range of motion, and changes in the patients' ambulatory status as measured using a nominal scale of four categories. The therapeutic effects of exercise according to each of the three approaches were compared using descriptive and nonparametric statistical methods. No substantial advantage could be attributed to any one of the three therapeutic approaches.

Reaction and movement times in patients with hemiparesis for unilateral and bilateral elbow flexion.

BACKGROUND AND PURPOSE: This work was designed to study the effects of bilateral elbow flexion on the reaction and movement times of the impaired upper extremity of patients with hemiparesis. SUBJECTS: The subjects consisted of an experimental group of patients with hemiparesis (n = 25) and a control group of age-matched healthy volunteers (n = 26). METHODS: Each subject performed three sets of 16 elbow flexion trials. Two of these sets required unilateral movements, one for each upper extremity. The third set of movements required simultaneous elbow flexions of both upper extremities. In each trial, subjects were instructed to flex their elbows in response to an auditory signal from a supported initial position of 150 degrees through a goal orientation of 120 degrees. "Reaction time" was defined as the time between the auditory signal and movement initiation. "Movement time" was defined as the time between movement initiation and the completion of 30 degrees of elbow flexion. RESULTS: When subjects were asked to bilaterally flex their elbows, the reaction and movement times increased in both extremities. CONCLUSION AND DISCUSSION: It was speculated that in patients with hemiparesis, movement time of the nonparetic extremity in the bilateral task is limited by the rate of performance of the paretic extremity. The decrease in speed of these performance-determining variables in the bilateral task warrants consideration during physical therapy intervention for patients with hemiparesis.

Electromyographic responses of distal ankle musculature of standing hemiplegic patients to continuous anterior-posterior perturbations during imposed weight transfer over the affected leg.

This study was undertaken to evaluate the influence of weight shift over the affected leg of standing hemiplegic patients on the electromyographic responses of the medial gastrocnemius and tibialis anterior muscles during continuous anterior-posterior movements of the base of support. Recordings were taken from 10 hemiplegic subjects and from 9 healthy subjects of comparable age. Each subject was first tested standing with both feet on a level surface and then with either leg (in healthy subjects) or the unaffected leg (in hemiplegic subjects) raised on a step. The second testing position caused unloading of the elevated leg and weight shift, that is, loading of the other leg. The measured variables were modulation of muscular activity, determined by a modulation index formulated for that purpose, and the relative amount of integrated electromyographic activity in each muscle. Changes in both variables in the uneven stance position as compared with even stance, occurred primarily in the unaffected (unloaded) leg in the hemiplegic subjects. These changes were comparable to changes in the unloaded leg of the healthy subjects. Thus, imposed loading on the affected leg of the hemiplegic subjects did not significantly improve either the reduced modulation or the relatively low IEMG activity of the investigated muscles. Further studies are required to evaluate the contribution of weight shift to recovery of postural responses in the affected leg of hemiplegic patients.

The surgical control of acute epileptic foci in the cat's cerebral cortex.

Topectomy is the treatment of choice for patients suffering from intractable focal epilepsy not responding to pharmacological treatment. A disadvantage of this method is the neurological deficit produced by excision of functional neurons. For this reason the excision of epileptic foci in vital cortical regions is avoided. Thus patients suffering from intractable focal epilepsy in the motor area do not, as yet, have a satisfactory medical or surgical solution to their problem. The purpose of this work is to suggest a different surgical approach on the basis of new data regarding vertical neural connections in the cortex that are vital to the maintenance of the epileptic foci. This possibility has been investigated so far only in acute animal experiments with the intention of applying this method next in chronic animal experiments and then, if successful, in human beings.

Induction of semichronic epileptic foci using cobalt oxide.

This paper describes a new method for production of semichronic epileptic foci in the cerebral cortex of cats. Cortical lesions that turned into epileptic foci were induced by extradural application of cobalt oxide powder. These lesions extended through the entire depth of the gray matter, but did not cause gross macroscopic damage. The cobalt oxide powder was removed from the dura mater 7 days after its application, at which time the lesion already showed epileptic activity; this activity did not diminish 7, 14, or 21 days later. Testing of epilepsy was done with a special procedure that allowed work with anesthetized animals. Before treatment with cobalt oxide began, the maximal dose of convulsant drug that would not cause an epileptic electrocorticogram response was determined for each animal (the "trigger dose"). Subsequent testing of potential epileptic foci consisted of monitoring the electrocorticographic responses to rapid intravenous injections of the trigger convulsant dose. The success of the present method in production of epileptic foci is evaluated by several criteria and is compared with other methods.

Surgical control of semichronic epileptic foci in the cat's sensorimotor cortex.

The present work was undertaken in order to find out whether delicate subpial incisions can be used to stop the epileptic activity of cortical lesions induced by cobalt oxide. Epileptic foci were produced in cats by epidural application of cobalt oxide powder. The presence of epilepsy was demonstrated a week later in anesthetized cats by injections of a "trigger dose" of pentamethylenetetrazole. Performance of subpial incisions through the focus area immediately abolished all ongoing epileptic activity. Such activity could not be evoked again by subsequent injection of pentamethylenetetrazole trigger doses throughout a 2-week period. The practical implications of this result are discussed. Some theoretical consequences of the similarity between the response of penicillin foci and that of cobalt oxide foci to the application of subpial incisions were evaluated. Finally, an attempt is made to explain the differences between our results and those produced by other investigators who also attempted to inactivate cobalt lesions in the cortex.

Responses of ankle musculature of healthy subjects and hemiplegic patients to sinusoidal anterior-posterior movements of the base of support.

The responses of the medical gastrocnemius and tibialis anterior muscles to continuous sinusoidal perturbation of the base of support were studied in two groups of subjects, forty-two volunteers aged 20 to 84 years and 17 hemiplegic patients aged 52 to 81 years. EMGs were recorded while subjects stood on a platform oscillating in the anterior-posterior direction. Movement amplitude was adjusted to the maximum the subject could sustain without assisted support within the limits of the instrument. In healthy subjects, two basic activation modes were indicated: (a) a reciprocal contraction pattern in which activity of the medial gastrocnemius and tibialis anterior muscles was concentrated in the anterior and posterior half of the oscillation, respectively. This pattern prevailed in the younger subjects whose maximal movement amplitude reached the highest limit of the instrument; (b) a less discrete pattern, characterized by tonic contraction and periods of coactivation of the two muscles, was seen in older subjects who had difficulties in maintaining stance on the moving platform. The disruption of the discrete reciprocal response mode in this group of patients was related to decline in function of postural mechanisms with aging and demanded additional stiffening of the ankle join, presumably a manifestation of reduced automatism in favor of closer CNS modulation. The typical response mode in the sound leg of the hemiplegic patients was variable coactivation of the two muscles. In the afflicted leg, the establishment of a motor set was impaired: Low tone was associated with negligible muscular activity, although with more elevated tone, low level uniform cocontraction was evident.

Accuracy of reproducing hand position when using active compared with passive movement.

BACKGROUND AND PURPOSE: Evaluating proprioception is relevant to physical rehabilitation because of its significance in motor control. One method of proprioceptive testing involves having subjects either imitate or point at a joint position or movement which was presented via a passive movement. However, as the muscle spindles are subject to central fusimotor control, the proprioceptive system may be better-tuned to movements created by active muscular contraction than to passive movements. The objective of the present study was to determine whether accuracy of reproducing hand position is dependent on whether proprioceptive input is obtained via an active or a passive movement. METHOD: Thirty-nine healthy volunteers (mean age (+/- SD) 24.6 (+/- 3.6) years) participated in the study. Subjects' right hands, which were obscured from view, were acoustically guided to five targets on a digitizer tablet with either an active or passive upper extremity movement. Subjects were then asked to reproduce the targets' location by either reaching to them with the unseen hand or by use of a laser beam. Distance from target and angular deviations were calculated in both absolute and relative terms. Repeated measures analysis of variance (ANOVA) was performed for each variable followed by predetermined contrasts. RESULTS: Comparison between the active and passive conditions when reconstruction of target location was guided kinaesthetically indicates significant differences in absolute distance, range and angular deviation. The comparison when reconstruction of target location was guided visually indicates significant differences in absolute distance, absolute angle and angular deviation. CONCLUSIONS: The ability to reproduce hand position accurately is enhanced when position is encoded by active upper extremity movement compared with passive movement. The results have implications for the design of strategies for evaluating as well as treating patients with impaired proprioception and limited movement.

Visual and kinesthetic control of goal-directed movements to visually and kinesthetically presented targets.

The study investigated the contribution of kinesthetic and visual input to the performance of reaching movements and identified rules governing the transformation of information between these two sensory modalities. The study examined the accuracy by which 39 subjects reproduced locations of five targets in a horizontal plane. Mode of target presentation and feedback during reproduction of a target's location was either visual, kinesthetic or a combination of both modalities. Thus, it was possible to examine performance when target presentation and reproduction involved feedback from the same sensory modality (intramodal) as well as from different sensory modalities (intermodal). Errors in target reproduction were calculated in terms of distance and systematic biases in movement extent. The major findings of the study are (1) Intramodal reproduction of a target's location on the basis of kinesthetic feedback is somewhat less accurate than intramodal reproduction on the basis of visual feedback (2) Intermodal performance is significantly less accurate than intramodal performance. (3) Accuracy of performance does not depend on the direction of information transfer between sensory modalities. (4) Intermodal performance is characterized by systematic biases in extent of movement which are dependent on the direction of information transfer between modalities. (5) When presentation of the target's location is bimodal, reproduction is adversely affected by the conflicting input. The results suggest that transformation rules, used to combine input from various sensory modalities, depend on environmental conditions and attention.