Signals of motor command bias joint position sense in the presence of feedback from proprioceptors.

Joint position sense is believed to be mediated by muscle afferent signals. Because a "phantom" hand produced by a sensory and motor nerve block appears to move in the direction of voluntary effort, signals of "motor command" or "effort" can influence perceived joint position. To determine whether this occurs when sensory signals are available, three studies assessed position sense when motor command and afferent signals were available, but joint movement was prevented. First, the hand was positioned to stop movement at the proximal joint of the middle finger, and movement at the distal joint was impossible because the muscles had been "disengaged". Voluntary efforts produced illusory position changes in the direction of the effort (12.6 +/- 2.0 degrees distal joint; 12.3 +/- 2.3 degrees proximal joint for efforts at 30% maximum; means +/- SD). Second, when subjects attempted to move the index finger under isometric conditions, the index finger appeared to move 7.4 +/- 1.2 degrees in the direction of efforts. These illusions graded with the level of effort (10 or 30% maximum) and far exceeded any real joint movement. Finally, because changes in muscle afferent feedback might have accompanied the voluntary efforts, all forearm and hand muscles were completely paralyzed by locally infused rocuronium. During paralysis, passive wrist position was signaled accurately, but, during attempted efforts (30% maximum), perceived wrist position changed by 9.7 +/- 4.9 degrees . Before paralysis, isometric efforts changed it by 6.7 +/- 3.6 degrees . Thus all studies concur: when joint movement is prevented, signals of motor command contribute to joint position sense.

Principles of brain plasticity in improving sensorimotor function of the knee and leg in healthy subjects: a double-blind randomized exploratory trial.

BACKGROUND: Principles of brain plasticity is used in the treatment of patients with functional limitations to improve sensorimotor function. Training is included in the treatment of knee injury to improve both patient-reported function and sensorimotor function. However, impairment in sensorimotor function often persists despite training. Therefore, it was suggested that training programs need to be more effective to improve sensorimotor function after knee injury. The aim of the current study was to investigate if principles of brain plasticity that have been successfully used on the hand and foot to improve sensorimotor function can be applied on the knee. We hypothesized that temporary anesthesia of the skin area above and below the knee would improve sensorimotor function of the ipsilateral knee and leg. METHODS: In this first double-blind exploratory study, 28 uninjured subjects (mean age 26 years, range 19-34, 50% women) were randomized to temporary local cutaneous application of anesthetic (EMLA) (n = 14) or placebo cream (n = 14). Fifty grams of EMLA, or placebo, was applied on the leg 10 cm above and 10 cm below the center of patella, leaving the area around the knee without cream. Measures of sensory function (perception of touch, vibration sense, knee kinesthesia) and motor function (knee muscle strength, hop test) were assessed before and after 90 minutes of treatment with EMLA or placebo. The paired t-test was used for comparisons within groups and the independent t-test for comparisons between groups. The number of subjects needed was determined by an a priori sample size calculation. RESULTS: No statistically significant or clinically relevant differences were seen over time (before vs. after) in the measures of sensory or motor functions in the EMLA group or in the placebo group. There were no differences between the groups due to treatment effect (EMLA vs. placebo). CONCLUSION: We found no effect of temporary cutaneous anesthesia on sensorimotor function of the ipsilateral knee and leg in uninjured subjects. The principles used in this study remain to be tested in subjects with knee injury.

Long-lasting tolerance to alcohol following a history of dependence.

Tolerance to alcohol effects is one of the defining features of clinical alcohol dependence. Here, we hypothesized that the post-dependent state may include tolerance to sedative-hypnotic alcohol actions. To address this question, we used a recently developed animal model in which repeated cycles of alcohol intoxication and withdrawal trigger long-lasting behavioral plasticity. This animal model shares important features with the clinical condition. Animals were exposed to 7 weeks of intermittent alcohol vapor, allowed to recover for 3 weeks, and tested in protracted abstinence to exclude contributions from acute withdrawal. Post-dependent and control rats were injected with a hypnotic dose of alcohol (3 g/kg), and the loss of righting reflex (LORR) was recorded, blood alcohol levels were monitored, and the elimination rate was calculated. Post-dependent animals showed a decrease in LORR. Alcohol metabolism and elimination kinetics did not differ between groups. In conclusion, a history of alcohol dependence induces long-lasting hypnotic tolerance. This process may play an important role in maintaining the dependent state.

Effects of Parkinson's disease and levodopa on functional limits of stability.

BACKGROUND: The voluntary, maximum inclined posture reflects the self-perceived limits of stability. Parkinson's disease is associated with small, bradykinetic postural weight shifts while standing but it is unclear whether this is due to reduced limits of stability and/or to the selection of abnormal strategies for leaning. The aim of this study was to investigate the effects of Parkinson's disease and levodopa medication on voluntary limits of stability and strategies used to reach these limits. METHODS: Fourteen subjects with Parkinson's disease (OFF and ON levodopa) and 10 age-matched controls participated in the study. Functional limits of stability were quantified as the maximum center of pressure excursion during voluntary forward and backward leaning. Postural strategies to achieve functional limits of stability were assessed by (i) body segments alignment, (ii) the difference between center of pressure and center of mass in preparation for a lean, (iii) the timing and the velocity of the preparation phase. FINDINGS: Functional limits of stability were significantly smaller in subjects with Parkinson's disease compared to control subjects. Subjects with Parkinson's disease maintained their stooped posture while leaning, initiated leaning with a smaller difference between center of pressure and center of mass and had a slower leaning velocity compared to control subjects. Levodopa enlarged the limits of stability in subjects with Parkinson's disease because of an increase in maximum forward, but not backward leans, but did not significantly improve postural alignment, preparation for a leaning movement, or velocity of leaning. INTERPRETATION: Parkinson's disease reduces functional limits of stability as well as the magnitude and velocity of postural preparation during voluntary, forward and backward leaning while standing. Levodopa improves the limits of stability but not the postural strategies used to achieve the leaning.

Disrupted integration of sensory stimuli with information about the movement of the body as a mechanism explaining LSD-induced experience.

LSD (lysergic acid diethylamide) is a model psychedelic drug used to study mechanism underlying the effects induced by hallucinogens. However, despite advanced knowledge about molecular mechanism responsible for the effects induced by LSD and other related substances acting at serotonergic 5-HT2a receptors, we still do not understand how these drugs trigger specific sensory experiences. LSD-induced experience is characterised by perception of movement in the environment and by presence of various bodily sensations such as floating in space, merging into surroundings and movement out of the physical body (the out-of-body experience). It means that a large part of the experience induced by the LSD can be simplified to the illusory movement that can be attributed to the self or to external objects. The phenomenology of the LSD-induced experience has been combined with the fact that serotonergic neurons provide all major parts of the brain with information about the level of tonic motor activity, occurrence of external stimuli and the execution of orienting responses. Therefore, it has been proposed that LSD-induced stimulation of 5-HT2a receptors disrupts the integration of the sensory stimuli with information about the movement of the body leading to perception of illusory movement.

Haptic Feedback Manipulation During Botulinum Toxin Injection Therapy for Focal Hand Dystonia Patients: A Possible New Assistive Strategy.

Abnormality of sensorimotor integration in the basal ganglia and cortex has been reported in the literature for patients with task-specific focal hand dystonia (FHD). In this study, we investigate the effect of manipulation of kinesthetic input in people living with writer's cramp disorder (a major form of FHD). For this purpose, severity of dystonia is studied for 11 participants while the symptoms of seven participants have been tracked during five sessions of assessment and Botulinum toxin injection (BoNT-A) therapy (one of the current suggested therapies for dystonia). BoNT-A therapy is delivered in the first and the third session. The goal is to analyze the effect of haptic manipulation as a potential assistive technique during BoNT-A therapy. The trial includes writing, hovering, and spiral/sinusoidal drawing subtasks. In each session, the subtasks are repeated twice when (a) a participant uses a normal pen, and (b) when the participant uses a robotics-assisted system (supporting the pen) which provides a compliant virtual writing surface and manipulates the kinesthetic sensory input. The results show (p-value using one-sample t-tests) that reducing the writing surface rigidity significantly decreases the severity of dystonia and results in better control of grip pressure (an indicator of dystonic cramping). It is also shown that (p-value based on paired-samples t-test) using the proposed haptic manipulation strategy, it is possible to augment the effectiveness of BoNT-A therapy. The outcome of this study is then used in the design of an actuated pen as a writing-assistance tool that can provide compliant haptic interaction during writing for FHD patients.

Effects of ethanol on kinaesthetic perception.

In normal subjects, alcohol increases handwriting size, but the mechanism is not understood. Here we show that the alcohol effect on handwriting can be explained by a selective impairment of kinaesthetic perception. Thirty volunteers (15 male, aged 18-29 years) took part in an open study. They were tested before and after a drink containing vodka intended to produce a blood alcohol concentration of about 80mg/100ml. Tests included kinaesthetic distance estimation, in which volunteers worked with preferred hand and arm behind a screen which hid their movements; visual distance estimation; and measures of handwriting and drawing. Blood alcohol concentration at 55min, based on breathalyser measurements, was 76.7mg/100ml (SD 9.8). When asked to move the hand and mark a distance of 10cm from a starting point, distances estimates increased by 7-10% (p 0.01). Similar increases were seen for writing words and drawing characters. Signatures were increased in height but not in length. Distances estimated visually were increased much less, by 3-4% (p 0.05). Tests of psychomotor performance indicated the expected effects of ethanol. These results suggest that ethanol affects writing size by reducing kinaesthetically perceived distances.

Incoordination of a sequential motor task in Parkinson's disease.

The quality of life in persons with Parkinson's disease (PD) has increased significantly with improved medicines. However, as the disease progresses difficulty in performing activities of daily life occur and occupational therapy intervention is sought (Deane et al., 2001). Reviews describing the efficacy of occupational therapy intervention in PD are inconclusive (Murphy and Tickle-Degnen, 2001; Gaudet, 2002). The purpose of this study is to establish an occupational therapy protocol for PD based upon research on motor control, sensory feedback and bradykinesia. As a first stage, the present study investigated the contribution of sensory feedback in generating the most prevalent symptoms of PD, that is, bradykinesia. Fast reach-to-grasp movement without kinesthetic or visual dependence in PD patients under on-drug and off-drug conditions were investigated. Seven normal participants and 11 patients with PD voluntarily participated in the study. Movements of the upper arm as a measure of reach, and movements of the index finger as a measure of grasp were recorded using magnetic trackers. Compared to the normal participants, this index to upper arm movement relationship was severely disturbed in the patients with PD and was improved following medications. Inter-onset latency (IOL), that is, the time lag between the initiation of upper arm movement and index movement, was significantly longer in PD patients compared to normal subjects. Medications reduced IOL which lead to improvement of the relationship of upper arm and index. The results suggest that bradykinesia is due to the breakdown of co-ordination between joint movements as a result of presumably slow executive processing of motor programmes. Individual joint movements are initiated out of sequence resulting in uncoordinated movements even with antiparkinsonian drugs. It is suggested that occupational therapy intervention in PD patients should be directed to occupations that require co-ordination of joint movements essential for successful completion of various activities of daily living tasks.

Parkinson's disease: reorganization of the reach to grasp movement in response to perturbation of the distal motor patterning.

This study assessed the kinematic changes to the reach to grasp movement in response to a perturbation of object size in 15 Parkinson's disease (PD) and 15 control subjects. For non-perturbed trials subjects reached 35 cm to grasp and lift either an illuminated small (0.7 cm) or large (8 cm) diameter cylinder. For perturbed trials (20%), illumination shifted unexpectedly from the small to the large or from the large to the small cylinder at the onset of the reach. For Condition One trials subjects were given no instructions as to which grasp to use. With perturbation, they thus naturally changed grasp from precision grip to whole hand prehension or vice versa. The results for the PD subjects indicated a slowness at the transition from one to another grasp. This contrasted to the smooth transitions when perturbation required only a change of grasp aperture (precision grip--Condition Two; whole hand prehension--Condition Three). PD subjects thus showed dysfunction in the suppression/activation of different grasp programs rather than deficits in the on-line modification of an operating program.

Detailed behavioral analysis of water maze acquisition under APV or CNQX: contribution of sensorimotor disturbances to drug-induced acquisition deficits.

N-methyl-D-aspartate (NMDA) receptor antagonists disrupt acquisition of the water maze and cause sensorimotor disturbances. In a detailed behavioral analysis in male rats, it was found that the NMDA antagonist DL-2-aminophosphonovaleric acid (APV) caused sensorimotor disturbances in behaviors required for maze performance and that these correlated with acquisition impairments in both hidden and visible platform versions of the maze. Behavioral disturbances included thigmotaxic swimming, swimming over and deflecting off the platform, abnormal swim behavior, and hyperactivity. Rats familiar with the behavioral strategies involved in the task performed normally under APV. The results are consistent with the known role of NMDA receptors in sensorimotor mechanisms and suggest that drug-induced sensorimotor disturbances contributed to poor acquisition scores in naive rats. NMDA may contribute to but does not appear to be essential for spatial learning in the water maze.

Interaction between recovery from behavioral asymmetries induced by hemivibrissotomy in the rat and the effects of apomorphine and amphetamine.

Spontaneous and drug-induced turning behavior and thigmotactic scanning were tested either acutely (4-6 hr) or chronically (9 days) after unilateral removal of vibrissae in rats. Rats that were tested acutely scanned more with the intact vibrissae side. This asymmetry was reduced in rats that were tested chronically, indicating behavioral recovery. The indirect dopamine agonist amphetamine induced a reversed asymmetry after 9 days because the animals then scanned more with the side lacking the vibrissae. Postsynaptic doses of apomorphine administered to acutely tested rats induced more scanning with, and more turning toward, the intact vibrissae side. A negative correlation was found in the chronically tested rats between the asymmetry in spontaneous scanning and the asymmetry after apomorphine. Nonrecovered rats showed indications of a reversal after apomorphine. The results are discussed in relation to mechanisms of neural plasticity in the basal ganglia, such as receptor supersensitivity and changes in nigrostriatal afferents.

The effects of dextroamphetamine on kinesthetic figural aftereffects.

The effect of dextroamphetamine, primarily a central stimulant, on kinesthetic figural aftereffects (KFAEs) was examined. The subjects were selected after preliminary testing with the Eysenck Personality Inventory and were classified into three groups: extraverts, ambiverts, and introverts. d-Amphetamine was used at three dose levels and a control group was included for purposes of comparison. The 3 X 4 randomized block design was replicated ten times. KFAEs were measured under two sets of conditions, i.e., before and after the induction experience. The results support the following conclusions: (1) neither personality grouping nor drug treatment during preinduction trials significantly affected KFAE; (2) both types of variables were, however, significantly related to behavior during the postinduction trials; (3) the extraverted subjects showed larger KFAEs than ambiverted and introverted subjects under placebo condition; (4) the extent of KFAE was reduced in extraverted and enhanced in introverted subjects under the influence of the drug; (5) there were significant interactions between the drug treatments and personality variables in effects on KFAE.

Caffeine differentially affects kinesthetic aftereffect in high and low impulsives.

The effects of caffeine on kinesthetic aftereffect (KAE) were examined. Following a between-subjects design, high and low impulsive male postgraduate students were administered placebo and four doses of caffeine (1, 2, 3 and 4 mg/kg body weight) in a laboratory situation. A double blind procedure was adopted for drug administration. The study supports the following conclusions: (1) caffeine reduces KAE in high impulsive subjects; (2) the larger dose of caffeine (4 mg/kg) enhances KAE in low impulsive subjects; (3) caffeine produces profound effects on the performance of high impulsives; (4) caffeine leads to different dose-response trends in the two groups.

The effect of smoking on perception of muscle tension.

It has been suggested that smoking may reduce affect in high-arousal situations by blocking peripheral physiological cues. The effects of smoking on perception of one type of physiological response, muscle activity, was evaluated in two studies. In study 1 male and female smokers were exposed to four conditions: high and low arousal crossed with smoking or deprivation. Results showed that smokers produce less muscle activity during high- than low-arousal situations, and that smoking reduced sensitivity to muscle activity in females, but enhanced it in males. These perception differences were not related to arousal as assessed by heart rate, which was elevated in all high-arousal situations. When compared to nonsmokers, smokers in a deprived state generate more muscle activity during the perception task, but showed no differences in sensitivity. These results represent the initial demonstration that smoking can alter the perception of physiological processes. Study 2 was designed to determine whether the effects of smoking were specific to muscle tension or indicative of a more generalized perceptual change. Perception of muscle tension and decibel levels were compared in smoking or deprived female smokers who were in the high-arousal situation. Results for muscle-tension perception in high-arousal situations were similar to those in study 1, but smoking did not alter perception of auditory stimuli.

Effect of clozapine on motor function in schizophrenic patients.

It is well established that clozapine is less likely than typical antipsychotic drugs to cause clinically discernible extrapyramidal side-effects. There is a paucity of data, however, on clozapine's motor effects. In this report we compare normal controls to groups of chronic schizophrenic patients treated with either typical antipsychotic drugs or with clozapine. Motor function was measured with a target-matching task, a test relying on submaximal sustained force control. Results indicated that patients on clozapine performed with significantly lower accuracy (greater variability) of force control. Even though the clozapine patients were treatment resistant to typical antipsychotic drugs, and many had a history of tardive dyskinesia, we postulate that the observed deficit is likely due to clozapine treatment rather than to earlier treatments or other factors. The observed force control deficit may be the result of an increase in myoclonus and a generally lower level of overall motor activity.

A simple, computer-assisted system for measuring latencies of contact placing.

A system for measuring the latencies of two components of contact placing, limb withdrawal and landing, is described. Timing functions are performed by a microcomputer, which also records and displays the latencies, and summarizes the data. Procedures for testing contact placing are also described, and data collected from morphine-treated, Long-Evans hooded rats are presented.

Effect of alcohol on the threshold for detecting angular acceleration.

We investigated the effects of a low blood alcohol level (mean BAC = 0.037%) on subjects' ability to detect acceleration and deceleration of angular motion. The angular motion thresholds of six alcohol and six placebo subjects, all of whom had private pilot certificates, were tested under double-blind conditions in an enclosed simulator apparatus prior to drinking, after drinking, and at a time when the BAC's of alcohol subjects had reached zero. Mean threshold values for the three threshold determination sessions were 0.282, 0.376, and 0.343 degrees.s-2 respectively for the alcohol subjects, and 0.263, 0.262, and 0.262 degrees.s-2 for placebo subjects. A significant alcohol x test-session interaction (p < 0.005) reflected the elevated thresholds shown by all alcohol subjects after consuming alcohol (p < 0.001). Of the six alcohol subjects, four continued to have elevated thresholds after their BAC's reached zero (p < 0.001). Alcohol and placebo subjects showed similar performance on the ancillary tasks of maintaining altitude and reporting a specified number when it appeared on a digital display. Both groups also reported that they had experienced similar levels of discomfort symptoms before and after drinking. The results indicate that a pilot's ability to detect angular motion can be compromised by low BAC levels, and this effect may continue for some pilots after their BAC reaches zero.

A comparison of some effects of three antimotion sickness drugs on nystagmic responses to angular accelerations and to optokinetic stimuli.

While the basic efficacy of antimotion sickness drugs is rooted in the reduction of motion sickness symptoms, adverse side effects are important practical considerations of their usage in aviation. This study examined the influence of three established antimotion sickness drugs on nystagmic eye movement responses to angular acceleration (whole-body movement) with vision either permitted or denied, and to optokinetic stimulation (visual field movement). Dimenhydrinate and promethazine hydrochloride, particularly at higher dose levels, reduced optokinetic nystagmus, thereby making less accurate the following ability of the eye. During whole-body motion in darkness, there was little placebo-drug difference in the vestibular response under alert conditions; under relaxed conditions, dimenhydrinate and promethazine hydrochloride produced significant declines in the vestibular eye movements. These same drugs also interfered with the ability of the individual to fixate adequately on a visual task during motion. Subjects who received a combination of promethazine plus d-amphetamine were able to suppress vestibular eye movements and maintain good visual fixation under the task condition. Thus, the effect of a drug on nystagmus may be a poor indicator of its value in preventing motion sickness. Moreover, assessments of antimotion sickness drugs for many practical situations should include, as a possible adverse side effect, the inability to maintain visual fixation during motion.

Do joint receptors modulate the motoneuron excitability?

The purpose of this study was to test the effect of joint receptor afferent discharge, during rest and during small excursion movement on kinesthetic sensation and on the excitability of alpha-motoneurons in the ankle joint in normal subjects. Movement kinesthesia was tested using a specially designed test that measured the delay time between the actual and the perceived movement during slow 5 degrees/sec), passive, 20 degrees movement excursion. These data were correlated to a second kinesthetic test using a visual analog scale in which the subject compared movements of the joint being tested and the contralateral control limb joint. The excitability of alpha-motoneurons was tested using soleus H-M recruitment curve with incremented electrical stimuli to the posterior tibial nerve at the back of the knee joint. The H-reflex recovery curve was also tested using double-identical stimuli of increasing interstimulus intervals. Joint receptors were desensitized by iontophoretic application of 3 cc. of 2% xylocaine using 5 mAmp direct current for 30 min, and movement kinesthesia and H-reflexes were tested over time up to 30 min after termination of iontophoresis. Movement kinesthesia was significantly decreased (p less than 0.05) following anesthesia, and the decrease lasted during the time of the experiment. No statistically significant changes were recorded in the H-M recruitment or H-reflex recovery curves. These results indicate that joint receptor afferents may lack the spontaneous activity recorded in other receptors, such as the skin and muscles, and do not provide position sensation at the ankle joint during rest. These results also indicate that joint receptor afferents may inform the central nervous system about movement sensation in the middle range, but this information has minimal effect on the excitability of the motoneurons as measured by H-reflexes.

Effects of levodopa on vividness of motor imagery in Parkinson disease.

INTRODUCTION: Motor imagery during functional magnetic resonance imaging is commonly used to understand the neural underpinnings of complex movements. This approach has recently been applied to individuals with Parkinson disease (PD) to better understand how brain function may relate to movement dysfunction. However, the ability of individuals with PD to imagine movements when "Off" dopamine replacement medication is poorly understood. Therefore, the primary purpose of the current study is to test the ability of people with PD to imagine movements while "On" and "Off" anti-Parkinson medication. METHODS: Vividness of imagery was assessed in 28 individuals with mild to moderate PD (Hoehn and Yahr stages 1-3) via the Kinesthetic Visual Imagery Questionnaire (KVIQ-20) both "On" and "Off" anti-Parkinson medication. Vividness of imagery of 32 age-matched older adults was also assessed. RESULTS: No differences in vividness of imagery were observed between "Off" and "On" medication states (p = 0.15). Imagery was similar between controls and PD both "Off" (p = 0.25) and "On" (p = 0.46) anti-Parkinson medication. A significant correlation was observed between imagery and disease severity while "On" anti-Parkinson medication (r = -0.49; p = 0.008). DISCUSSION AND CONCLUSIONS: Vividness of movement imagery was not different between "Off" and "On" anti-Parkinson medications or between PD and controls. These results suggest that people with PD are able to imagine similarly to older adults both when "On" and "Off" anti-Parkinson medication, and supports the use of motor imagery in the "Off" medication state.