帕金森病静止性震颤机理的模型仿真

目的研究帕金森病静止性震颤特征与人体反应迟缓的内在联系。方法结合上肢腕关节的动力学建模,研究腕关节内外翻方向自由度运动特征。引入人体自主控制环节,以控制系统的时滞概念模拟帕金森患者反应延迟特性,进行人体腕关节不自主运动的稳定性分析和动力学响应。结果通过时滞系统稳定性分析和数值求解,发现当反应延迟一定程度时,帕金森患者的腕关节将发生不自主震颤,与帕金森患者静止性震颤病症契合。结论帕金森病静止性震颤属于神经系统感觉和动作延迟引起。     

Attenuation of pathological tremors by functional electrical stimulation I: Method

In this study we explored the possibility of suppressing pathological tremors using closed-loop functional electrical stimulation (FES) to activate the tremorogenic muscles out-of-phase. A displacement signal monitored with a transducer was filtered so as to be “tuned” to the tremor frequency at the wrist or elbow. The filtered signal was used to amplitude-modulate the electrical stimulation. The design process was based on measurements of the open-loop frequency response characteristics of the forearm and hand to stimulation of the elbow and wrist flexors and extensors in a number of subjects. These data allowed us to identify closed-loop configurations, which attenuated 2–5 Hz tremors substantially, while only minimally attenuating functional movements in the 0–1 Hz range. There was a fairly delicate balance between efficacy and the risk of instability. However, designs were identified that offered enough tremor suppression and adequate immunity to muscle/load variations for the technique to be considered seriously for clinical application.     

The direction of oscillation in spiral drawings can be used to differentiate distal and proximal arm tremor

The assessment of the extent of involvement of the distal and proximal joints in a complex arm tremor is important clinically, as tremor generated around the distal and proximal arm joints can be differentially alleviated by surgical intervention to the thalamic and subthalamic targets, respectively. We observed that the tremor present in spiral drawings shows a diagonal directional preference. We hypothesized that the directional preference of tremor within spiral drawings could be related to the involvement of different arm joints. In this study, we tested this hypothesis by: (1) studying simulated tremulous drawings performed by healthy subjects with the joints selectively restrained; (2) recording surface EMGs from the forearm extensor and deltoid muscles during drawing; and (3) mathematical modelling the kinematics of the arm in 2D drawings. Our data showed that a "main diagonal" axis of orientation of the tremor along the orientation of the forearm indicates a predominantly proximal tremor driven by the shoulder, and a "cross diagonal" axis of orientation of tremor (i.e. perpendicular to the forearm) indicates that the tremor is predominantly distal and driven by the elbow or wrist. We conclude that the spiral drawing task can be used as an objective and quantitative method for differentiating the involvement of the proximal and distal arm joints in complex arm tremors.     

Transient reversal of the stretch reflex in human arm muscles.

1. Load perturbation responses can violate the law of reciprocal innervation between antagonist muscles under particular conditions. Thus flexor and extensor muscles of wrist and elbow joints are reflexly coactivated by the impact of a ball on the hand during a catching task. The aim of this study was to determine whether reflex coactivation can be preset within the central nervous system (CNS) or whether it is entirely due to the peripheral stimulus. To this end, we studied the behavior of stretch reflex responses of arm muscles evoked by torque motor perturbations applied before and during the catching task. 2. Subjects were instructed to catch a ball dropped from 1.6 m. A torque motor delivered perturbations to the elbow joint, resulting in angular motion at both elbow and wrist joints because of their dynamic mechanical coupling. Two series of experiments were performed that differed in the perturbation waveform. In the first series, a single torque pulse could be randomly applied at different times during the task. The corresponding responses were recovered by subtracting the average of the unperturbed trials from the averages of perturbed trials. In the second series of experiments, a train of pseudorandom pulses was applied continuously during each trial. The time-varying impulse responses were computed at 20-ms intervals by cross-correlation methods. 3. The pattern of the short-latency electromyographic responses evoked by either single pulses or pseudorandom perturbations obeyed the law of reciprocal innervation of antagonist muscles under basal conditions. However, the pattern of the responses evoked by the same perturbations around the time of ball impact on the hand consisted of a substantial coactivation of both stretched and shortening muscles. Reflex coactivation resulted from response patterns that differed at different joints. At the elbow, reflex coactivation resulted from a transient reversal of the direction of the short-latency responses of flexor muscles, with little changes of the responses of extensor muscles. At the wrist, instead, reflex coactivation resulted from simultaneous changes in the response waveform of both flexor and extensor muscles. 4. The peripheral conditions associated with the applied perturbations were constant before the time of ball impact. Thus, because the changes of the stretch reflex responses began before that time, they must have been generated within the CNS. It is here hypothesized that the reversal of the reflex responses is centrally gated by switching from the pathways of reciprocal inhibition to those of coactivation of antagonist alpha-motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

The onset of voluntary reactive movement is temporally influenced by the central oscillation in action tremor caused by multiple sclerosis

The influence of oscillatory activity in the motor system on the generation of voluntary movement has been previously studied by revealing temporal coupling between voluntary movements and associated physiological or pathological tremor. The present study aims to investigate whether there is any temporal correlation between the onset of a rapid reactive movement and the action tremor at the wrist in patients with multiple sclerosis (MS). In 13 MS patients, their reactive wrist movements and tremor were simultaneously recorded during a visually cued simple reaction time task. Significant correlation was found between the tremor-related and non-tremor-related measurements of the wrist movement. The onset of reactive movement was unevenly distributed over the tremor cycle peaking at 177 degrees in the direction opposite to the reactive movement, suggesting a temporal coupling between the reactive movements and tremor. No significant difference in reaction time was found between voluntary flexion and extension movements, and no significant differences in the mean values or the standard deviations of the reaction time between the movements in-phase and out-of-phase with tremor were detected, suggesting that entrainment of the spinal motor neurons is not influenced by tremor activity. In conclusion, in MS action tremor, the timing of the initiation of a rapid voluntary movement may be influenced by the pathological oscillator at a supra-spinal level.     

The effects of unilateral muscle fatigue on bilateral physiological tremor

The aim of this study was to examine the post-exercise effects of fatiguing the wrist extensor muscles of a single arm on postural tremor and muscle activity in both arms. Previous research has shown that, for neurologically normal subjects, the tremor seen within a single limb segment is uncorrelated to that seen contralaterally. However it has been speculated that some bilateral relation does exist, and that the nature of the relation may only become evident under conditions where the neuromuscular system is perturbed. To further investigate this potential bilateral relation, seven healthy subjects were required to adopt a bilateral postural pointing position after exercise-induced fatigue of the wrist extensor muscles of a single arm. Tremor from the forearm, hand and finger segments of each arm, surface EMG activity from extensor digitorum (ED) of each arm, and blood lactate data were collected prior to and after the exercise intervention. The main result was that fatiguing the distal muscles of one arm resulted in a bilateral increase in both the physiological tremor and ED activity. The change in tremor was confined to the index finger with no change in the tremor for the hand or forearm segments of either arm. While three peaks were seen in the frequency profile of the finger tremor, the effects of fatigue were confined to an increase in the peak power of the neurally generated 8–12 Hz tremor component. The contralateral increase in muscle activity was also reflected by a change in the frequency profile of the EMG output, with an increase in the peak power of both muscles following exercise of the wrist extensors of a single arm. The bilateral increases in physiological tremor and EMG activity of ED were only observed during the bilateral pointing task, with no changes in tremor or EMG activity seen for the non-exercised limb during the unilateral exercise protocol. The specificity of the resultant increases in the neurally generated 8–12 Hz component of finger tremor amplitude and EMG activity, coupled with the lack of any changes in tremor for the more proximal arm segments, indicate that these bilateral effects were mediated by an increase in the central neural drive to both limbs. Together this set of results challenges the general assumption of bilateral independence of tremor production, and further illustrate the task dependent nature of exercise-induced fatigue.     

Computer-based test-bed for clinical assessment of hand/wrist feed-forward neuroprosthetic controllers using artificial neural networks

Neuroprosthestic systems can be used to restore hand grasp and wrist control in individuals with C5/C6 spinal cord injury. A computer-based system was developed for the implementation, tuning and clinical assessment of neuroprosthetic controllers, using off-the-shelf hardware and software. The computer system turned a Pentium III PC running Windows NT into a non-dedicated, real-time system for the control of neuroprostheses. Software execution (written using the high-level programming languages LabVIEW and MATLAB) was divided into two phases: training and real-time control. During the training phase, the computer system collected input/output data by stimulating the muscles and measuring the muscle outputs in real-time, analysed the recorded data, generated a set of training data and trained an artificial neural network (ANN)-based controller. During real-time control, the computer system stimulated the muscles using stimulus pulsewidths predicted by the ANN controller in response to a sampled input from an external command source, to provide independent control of hand grasp and wrist posture. System timing was stable, reliable and capable of providing muscle stimulation at frequencies up to 24 Hz. To demonstrate the application of the test-bed, an ANN-based controller was implemented with three inputs and two independent channels of stimulation. The ANN controller's ability to control hand grasp and wrist angle independently was assessed by quantitative comparison of the outputs of the stimulated muscles with a set of desired grasp or wrist postures determined by the command signal. Controller performance results were mixed, but the platform provided the tools to implement and assess future controller designs.     

Pattern of projections of group I afferents from forearm muscles to motoneurones supplying biceps and triceps muscles in man

Summary (1) Two independent methods were used, in man, to assess the modifications of the excitability of biceps and triceps brachii motoneurone pools following the stimulation of group I afferents coming from muscles acting at the wrist: (a) the modifications of the excitability of a motoneuronal population were studied using a reflex technique, (b) the modifications of the excitability of an isolated motor unit were estimated using a post-stimulus time histogram (p.s.t.h.) method. (2) The activation of group I afferents contained in the median nerve, originating from wrist flexors and pronators, resulted in a strong, short-latency facilitation of the biceps brachii motoneurones. A similar effect was also evoked by stimulation of group I afferents in the radial nerve, distally to the branch supplying the brachio-radialis muscle. The latency of both median and radial-induced facilitations is compatible with a monosynaptic linkage. (3) The stimulation of group I afferents in the median or the radial nerves produced inhibition of triceps motoneurones, with a latency compatible with a disynaptic linkage. (4) The prolonged vibration of the tendon of the flexor carpi radialis (FCR) or of the extensor carpi radialis (ECR) raised the threshold for both the facilitation of biceps and the inhibition of triceps motoneurones. The same pattern of excitatory and inhibitory convergence could also be obtained when the electrical conditioning stimulus to the median or radial nerves was replaced by a tap applied to the tendons of FCR or ECR respectively. Both results suggest that the conditioning fibres were Ia fibres. (5) The pattern of distribution of Ia afferents from muscles acting at the wrist onto motoneurones of muscles acting at the elbow has been compared to that described in the cat and monkey. A comparison has also been made between Ia connections of muscles acting at different joints in the upper and lower limb in man. The differences are discussed in relation to the manipulating capacity of the hand.     

Interhemispheric inhibition in human wrist muscles

The interhemispheric interactions between homologous wrist extensor and flexor muscles representations in the right and left primary cortex (M1) were studied using a paired-pulse transcranial magnetic stimulation in healthy subjects. The magnitude of interhemispheric inhibition (IHI) was studied in 9 right-handed subjects at short (10 ms, SIHI) and long (40 ms, LIHI) interstimulus intervals between the magnetic conditioning (CS) and test stimulus in the motor dominant to non-dominant cortex and vice versa, while the right or left hand was at rest or performing a unimanual sustained tonic contraction (holding a pen with the hand contralateral to the CS). A bidirectional powerful interhemispheric inhibition could be elicited at the short and long IHI phases (SIHI and LIHI) in wrist extensor and flexor muscles in most of the subjects at rest. SIHI but not LIHI was significantly bidirectionally reduced during unimanual contraction of the hand contralateral to the CS stimulation in comparison with rest. The amount of IHI after the stimulation of the “non-dominant” right hemisphere was not reduced in comparison with IHI after stimulation of the “dominant” left hemisphere whatever the active or resting condition. IHI directed to the wrist muscles had a similar level than IHI directed to digit muscles (FDI) at rest. Our data indicate that contralateral wrist muscles activity evokes a global, bidirectional reduction in IHI which was more pronounced for SIHI. These results provide additional evidence that changes in interhemispheric interactions between the M1s are involved in the control of unimanual movements including suppression of unwanted motor activity in the opposite limb during unilateral movements.     

The effects of weight load and joint immobilization on reorganization of postural tremor

To investigate change in coordinative strategies due to wrist immobilization and index loading, postural tremors from the index, hand, and forearm were recorded during different postural holding tasks. The wrist joint was immobilized with a thermoplastic splint in the constrained condition, and a copper mass of 100 grams was applied to the index finger in the loaded condition. The structures of the postural tremors of all upper limb segments among the unloaded-unconstrained, unloaded-constrained, loaded-unconstrained, and loaded-constrained conditions were compared. Index loading exaggerated index/forearm postural tremor, while the load-induced tremor enhancement was no longer evident for wrist immobilization. In the unloaded condition, wrist immobilization resulted specifically in enhancement of carpal postural tremor, rather than in the index and forearm. Index loading induced a marked tremor peak and relative power in the range of 5-8 Hz. Wrist immobilization potentiated the carpal tremor peak of 1-4 Hz in association with enhancement of carpal-forearm mechanical coupling. In light of structural changes in postural tremor, our data suggest that (1) a wrist splint is effective to counteract load-induced enhancement of postural tremor, and (2) freezing of the wrist joint might facilitate compensatory strategies to minimize passive fluctuation transmission from the carpal to index.     

A case of psychogenic tremor associated with blepharospasm and myoclonus: an analysis with surface electromyogram

We report a 25-year-old woman with an unusual complex psychogenic movement disorders consisting of blepharospasm, tremor, and myoclonus. The tremor appeared in both arms and legs with resting, kinetic, and postural tremor of a variable amplitude, direction, and frequency. The analysis of the arm tremor with surface electromyogram revealed that it consisted of reciprocal and alternating contraction of the wrist flexor and extensor. No apparent co-activation of agonist-antagonist muscles could be seen at the onset of the tremor at rest or at its appearance while performing diadochokinesis.     

Neurophysiology of orthostatic tremor. Influence of transcranial magnetic stimulation

A 74-year-old patient suffers from painful muscle cramps when he stands since 30 years. He has no visible tremor but 16 Hz burst activity on EMG, indicating orthostatic tremor. Previous diagnosis was hysteria, stiff person syndrome or dystonia. This shows that EMG during standing should be part of the examination of patients with stiff muscles or muscle cramps. Tremor was not strictly orthostatic. It appeared in back muscles while sitting, when the patient supported a weight with outstretched arms. Phase between muscles differed between normal standing and standing on heels. Subthreshold transcranial magnetic stimulation modulated timing of the tremor bursts and inhibited them at higher intensity stimulation.     

A new method for selective measurement of joint movement in hand tremor in Parkinson's disease patients

Parkinson's disease (PD) is a progressive degenerative disorder of the central nervous system with tremor being one of its four main clinical features. Currently used methods can directly evaluate tremor amplitude and frequency but not joint movement in the affected limb. Measurement of joint movement facilitates the location of muscle groups that participate in PD tremor and this is important for treatment with local botulinum toxin injections. We developed and tested a method that measured tremor amplitude and frequency in a specific joint of the hand in PD patients. The tremor analysis method was based on force transducers adapted to record rest tremor of the wrist and metacarpophalangeal joints in two degrees of freedom for each joint. Direct measurements of joint movement in the hand can evaluate tremor amplitude and frequency and also locate the muscle groups that are most active in tremor movement, thus enabling their local treatment.     

Intraoperative acceleration measurements to quantify improvement in tremor during deep brain stimulation surgery

Deep brain stimulation (DBS) surgery is extensively used in the treatment of movement disorders. Nevertheless, methods to evaluate the clinical response during intraoperative stimulation tests to identify the optimal position for the implantation of the chronic DBS lead remain subjective. In this paper, we describe a new, versatile method for quantitative intraoperative evaluation of improvement in tremor with an acceleration sensor that is mounted on the patient’s wrist during surgery. At each anatomical test position, the improvement in tremor compared to the initial tremor is estimated on the basis of extracted outcome measures. This method was tested on 15 tremor patients undergoing DBS surgery in two centers. Data from 359 stimulation tests were acquired. Our results suggest that accelerometric evaluation detects tremor changes more sensitively than subjective visual ratings. The effective stimulation current amplitudes identified from the quantitative data (1.1 ± 0.8 mA) are lower than those identified by visual evaluation (1.7 ± 0.8 mA) for similar improvement in tremor. Additionally, if these data had been used to choose the chronic implant position of the DBS lead, 15 of the 26 choices would have been different. These results show that our method of accelerometric evaluation can potentially improve DBS targeting.     

Vib-bracelet: a passive absorber for attenuating forearm tremor

Tremor is a rhythmic, involuntary, oscillatory movement of a limb produced by alternating contractions of reciprocally innervated muscles. More than 4% of the population over 40 years old suffer from tremor. There is no cure for most tremors, and while psychological therapy is sometimes helpful, tremors are usually treated with either medication or invasive surgery including thalamotomy and deep brain stimulation. Both medications and surgery may have adverse effects, and thus, there is a growing interest in developing non-invasive vibration attenuation devices. This paper presents a passive absorber device for attenuating pronation/supination tremor, dubbed Vib-bracelet. It is based on the principles of dynamic vibration absorption and is tuned to the frequency of the tremor. Prototypes were manufactured and tested on a mechanical model of the human forearm. Simulations and experiments demonstrate the efficiency of the device in attenuating vibrations in the range of 4–6 Hz, which is the range of frequency of observed tremor, with maximum amplitude attenuation of 85%.     

Effects of proximal and distal muscles' groups contraction and mental stress on the amplitude and frequency of physiological finger tremor. An accelerometric study

Physiological finger tremor was assessed by two-dimensional solid accelerometry in 40 healthy normal subjects at rest (R) with the hand hanging over the armrest of a chair, in posture (P) with the arm rested on the armrest but the hand extended from the wrist, and finally adding proximal muscles contraction in extension (E) with the arm extended in front of the patient, each time with and without mental stress. The mean amplitude for physiological tremor, about 30 microns, was almost doubled by hand extension and increased by 4 to 5-fold by arm extension with further increase by mental stress in each position, which gives a good estimation of the contribution of proximal and distal muscles into the amplitude of physiological tremor. There was no significant effect of age between 20 and 60 years on tremor amplitude, but mean tremor frequency decreased significantly between 40 to 60 years. Mental stress increased amplitude but decreased tremor frequency of both across all position, possibly by increasing the synchronization of motor unit firing and by modifying the gain of the motoneurones and the stretch reflex as shown by electrophysiological studies.     

Hierarchical control of different elbow-wrist coordination patterns

The present paper focused on the role of mechanical factors arising from the multijoint structure of the musculoskeletal system and their use in the control of different patterns of cyclical elbow-wrist movements. Across five levels of cycling frequency (from 0.45 Hz up to 3.05 Hz), three movement patterns were analyzed: (1) unidirectional, including rotations at the elbow and wrist in the same direction; (2) bidirectional, with rotation at the joints in opposite directions, and (3) free-wrist pattern, which is characterized by alternating flexions and extensions at the elbow with the wrist relaxed. Angular position of both joints and electromyographic activity of biceps, triceps, the wrist flexor, and the wrist extensor were recorded. It was demonstrated that control at the elbow was principally different from control at the wrist. Elbow control in all three patterns was similar to that typically observed during single-joint movements: elbow accelerations-decelerations resulted from alternating activity of the elbow flexor and extensor and were largely independent of wrist motion at all frequency plateaus. The elbow muscles were responsible not only for the elbow movement, but also for the generation of interactive torques that played an important role in wrist control. There were two types of interactive torques exerted at the wrist: inertial torque arising from elbow motion and restraining torque arising from physical limits imposed on wrist rotation. These interactive torques were the primary source of wrist motion, whereas the main function of wrist-muscle activity was to intervene with the interactive effects and to adjust the wrist movement to comply with the required coordination pattern. The unidirectional pattern was more in agreement with interactive effects than the bidirectional pattern, thus causing their differential difficulty at moderate cycle frequencies. When cycling frequency was further increased, both the unidirectional and bidirectional movements lost their individual features and acquired features of the free-wrist pattern. The deterioration of the controlled patterns at high cycling frequencies suggests a crucial role for proprioceptive information in wrist control. These results are suppportive of a hierachical organization of control with respect to elbow-wrist coordination, during which the functions of control at the elbow and wrist are principally different: the elbow muscles generate movement of the whole linkage and the wrist muscles produce corrections of the movement necessary to fulfill the task. Received: 5 August 1997 / Accepted: 29 January 1998     

A new method for selective measurement of joint movement in hand tremor in Parkinson's disease patients

Parkinson's disease (PD) is a progressive degenerative disorder of the central nervous system with tremor being one of its four main clinical features. Currently used methods can directly evaluate tremor amplitude and frequency but not joint movement in the affected limb. Measurement of joint movement facilitates the location of muscle groups that participate in PD tremor and this is important for treatment with local botulinum toxin injections. We developed and tested a method that measured tremor amplitude and frequency in a specific joint of the hand in PD patients. The tremor analysis method was based on force transducers adapted to record rest tremor of the wrist and metacarpophalangeal joints in two degrees of freedom for each joint. Direct measurements of joint movement in the hand can evaluate tremor amplitude and frequency and also locate the muscle groups that are most active in tremor movement, thus enabling their local treatment.     

Selection of muscles for initiation of planar,three-joint arm movements with different final orientations of the hand

Muscle activities and joint rotations were examined at the shoulder, elbow, and wrist joints for pointing movements to targets in the horizontal plane. In such movements, multiple arm configurations are possible for a given target location. Thus, starting from the same initial configuration and for the same target location in space, the joint excursions could be varied. When no constraints were placed on the final orientation of the hand, the choice of muscles initially activated at the wrist joint was consistent with a function to resist inertial effects of proximal segment motion on the wrist joint. When subjects were asked to produce different final orientations of the hand for the same target location, the initial choice of muscles at the three joints was preserved in most trials, whether wrist flexion or extension was required to reach the final hand orientation. The relative onset times of muscle activity at the different joints were also not correlated with wrist excursion. This suggests a predetermined initial selection of muscles that is related to target location, not to joint angular excursion. The fact that the required final hand orientation was nevertheless achieved suggests that the planning of these pointing movements is not a unitary process, but is comprised of two components: a fixed initial muscle selection for a given target location in space, and a selection appropriate for the required joint excursions.     

The startle reaction to somatosensory inputs: different response pattern to stimuli of upper and lower limbs

Unexpected sensory inputs can generate a patterned startle reaction, aimed at protection and defense. Experimentally, it is usually triggered by auditory stimuli while the startle reaction to somatosensory inputs (SSS) has not received much attention so far. This may be in part due to the fact that somatosensory inputs inevitably cause local reactions, such as short and long latency reflexes and withdrawal reactions, which could interfere with recognition of the startle-related activity. Therefore, we have undertaken a study aimed at separating the SSS from other responses by exploring the responses that are common to somatosensory stimuli applied to different sites and examining the inhibitory effects of prepulse stimuli. In 13 healthy naive subjects, we applied electrical stimuli to the median nerve at the wrist (MW) or the posterior tibial nerve at the ankle (PT) and recorded from orbicularis oculi (OOC), masseter (MAS), sternocleidomastoid (SCM) and representative muscles of the limbs being stimulated (flexor carpi radialis for MW and tibialis anterior for PT). In random trials, we also applied prepulse stimuli, either a low-intensity auditory stimulus or low-intensity electrical stimuli, 100 ms before the SSS-eliciting stimulus. The pattern of SSS was different for upper and lower limb stimuli. While stimuli applied to MW induced a prominent reaction of the OOC, at a mean latency of 61.1 ms (SD = 16.3 ms), followed by the SCM at a mean latency of 83.3 ms (SD = 28.6 ms), those applied to the PT caused a small or absent response in the OOC and a consistent response of the SCM at a mean latency of 89.7 ms (SD = 30.1 ms). Prepulse stimuli effectively inhibited the responses of facial and neck muscles but only partially those of the wrist flexors to MW or the tibialis anterior to PT. Our results indicate that, although there are common neck and facial muscle reactions to somatosensory stimuli applied to upper and lower limbs, the pattern of the SSS differs according to the source of the input. Prepulse inhibition is more effective on the responses of neck and facial muscles than on the responses of limb muscles to somatosensory stimuli. These results could help in distinguishing between withdrawal and SSS reactions.