Atypical task-invariant organization of multi-segment tremors in patients with Parkinson’s disease during manual tracking

The objective of the study was to investigate the interplay between involuntary tremulous activities and task performance under volitional control for patients with Parkinson’s disease (PD) during position tracking. A volunteer sample of nine untreated patients and nine age-matched healthy subjects participated in this study. They performed a sinusoidal tracking maneuver with a shoulder and a static pointing task; meanwhile, a position trace of the index and accelerometer data in the upper limb were recorded to characterize tracking performance and postural–kinetic tremors. In reference to postural tremor, the kinetic tremor of control subjects during tracking was considerably modulated, leading to a lower regularity and greater spectral deviation. In contrast, patients with PD demonstrated greater postural and kinetic tremors than control subjects, and tremulous movements of the patients were comparatively task-invariant. The prominent coherence peak, which occurred at 8–12 Hz in control subjects, was atypically presented at 5–8 Hz for PD patients with poorer tracking performance. Functionally, congruency of position tracking was related to amplitude of kinetic tremor after subtracting from amplitude of postural tremor. In conclusion, task-dependent organization of tremulous movements was impaired in patients with PD. The inferior tracking performance of the patients correlated implicitly with kinetic tremor, signifying some sharing of neural substrates for manual tracking and tremor generation.     

Muscle spasms associated with Sudeck's atrophy after injury.

Four patients developed abnormal involuntary movements of a limb after injury. All subsequently developed sympathetic algodystrophy with Sudeck''s atrophy and then abnormal muscle spasms or jerks of the affected limb, lasting years. Sympathetic block in three patients did not relieve the abnormal movements. Two patients obtained partial recovery spontaneously, but the other two required surgery for relief. The pathophysiology of this condition remains to be determined but the evidence suggests that it is a distinct, disabling clinical syndrome.     

Tremor modulation in patients with Parkinson’s disease compared to healthy counterparts during loaded postural holding

Through examining tremor dynamics, the study sought to investigate the effects of load characteristics upon control strategies in patients with Parkinson’s disease (PD) during postural holding. Eleven untreated patients and eleven healthy adults conducted a static pointing task with an outstretched arm, with a manipulated load of 100 g on the index finger. Oscillatory activities in the upper limb were contrasted between the unloaded and loaded conditions. The results showed that PD patients demonstrated abnormal modulation of tremor amplitude in the finger, hand, and upper arm in the opposing load condition. When the load was applied, the PD patients presented a nearly opposite pattern of tremor coupling between limb segments, contrary to the normal release and enhancement of tremor coupling in the finger–hand and hand–forearm complexes, respectively. Principal component analysis suggested that normal postural tremors could be explained by a load-dependent component that had high communality with tremors of the distal segments. In contrast, major principal components of PD tremor were invariant to load addition. Multi-segment tremors in PD were atypically organized during loaded postural holding, signifying that coordinative control of the upper limb in the patients was impaired in the absence of exploitation of a germane distal strategy against inertial perturbation.     

Neuronal mechanisms of motor signal transmission in the thalamic ventrooral nucleus in spasmodic torticollis patients

A microelectrode technique was used to study the neuronal mechanisms of motor signal transmission in the ventrooral internus nucleus (Voi) of the motor thalamus during voluntary and involuntary pathological (dystonic) movements in patients with spasmodic torticollis. Voi cell elements proved highly reactive to various functional (mostly motor) tests. An activity analysis of 55 Voi neurons detected during nine stereotactic operations revealed, first, a difference in neuronal mechanisms of motor signal transmission for voluntary movements that do or do not involve the affected axial muscles of the neck and for passive and abnormal involuntary dystonic movements. Second, a sensory component was found to play a key role in the mechanisms of sensorimotor interactions during voluntary and involuntary dystonic head and neck movements activating the axial muscles of the neck. Third, rhythmic and synchronized activity of Voi neurons was shown to play an important role in motor signal transmission during voluntary and passive movements. The Voi nucleus was directly implicated in the mechanisms of involuntary head movements and tension of the neck muscles in spasmodic torticollis. The results can be used to identify the Voi nucleus of the thalamus during stereotactic neurosurgery in order to select the optimal destruction or stimulation target and to reduce the postoperative effects in spasmodic torticollis patients.     

Responses of the red nucleus neurons to stimulation of the paw pads of forelimbs before and after cerebellar lesions.

Cerebellar cortex ablation releases deep cerebellar nuclei of monosynaptic inhibition from Purkinje cells. Therefore, it strengthens excitatory influence from Interpositus Nucleus (IN) upon Red Nucleus (RN), which results in much higher facilitation of the rubro-spinal neurons. This causes a big increase of spontaneous discharge rate, and eliminates brakes of discharges from responses generated by somatosensory stimuli. These two changes destroy content and timing of feedback information flowing through the spino-cerebello-rubro-spinal loop. This false bias of the feedback information, very important for fast postural adjustment and coordination of ongoing movements executed by central motor program, may at least in part be responsible for abnormal motor behavior evoked by cerebellar damage. Hemicerebellectomy resulted in dramatically reduced spontaneous activity and responses to limb stimulation because of severing a major input to the red nucleus from deep cerebellar nuclei. Due to direct somatosensory input to magnocellular Red Nucleus (mcRN) from the spinal cord that bypassed the cerebellum, the latency of response to limb stimulation was not changed and the narrower receptive fields were still present.     

Tremor disorders. Diagnosis and management.

Tremor is commonly encountered in medical practice, but can be difficult to diagnose and manage. It is an involuntary rhythmic oscillation of a body part produced by reciprocally innervated antagonist muscles. Tremors vary in frequency and amplitude and are influenced by physiologic and psychological factors and drugs. Categorization is based on position, posture, and the movement necessary to elicit the tremor. A resting tremor occurs when the body part is in repose. A postural tremor occurs with maintained posture and kinetic tremor with movement. Various pathologic conditions are associated with tremors. Essential tremor, which is the most common, is postural and kinetic, with a frequency between 4 and 8 Hz, and involves mainly the upper extremities and head. Essential tremor responds to treatment with primidone, beta-blockers, and benzodiazepines. Parkinson''s disease causes a 4- to 6-Hz resting tremor in the arms and legs that responds to the use of anticholinergics and a combination of carbidopa and levodopa. Tremor can also be a manifestation of Wilson''s disease, lesions of the cerebellum and midbrain, peripheral neuropathy, trauma, alcohol, and conversion disorders. Treatment should be directed to the underlying condition. Stereotactic thalamotomy of thalamic stimulation is a last resort.     

Bilateral organization of physiological tremor in the upper limb

The bilateral patterns of physiological tremor in the upper limb of adults were examined under conditions where eight combinations of the elbow, wrist and index-finger joints of the right arm were braced using individually molded splints. The hypotheses tested were that: (a) coordination of upper-limb tremor involves (compensatory) coupling of intra- but not inter-limb segments, (b) splinting the respective joints of the right arm changes the organization of this synergy in both limbs, and (c) reducing the involvement of joint-space degrees of freedom through restricting their motion (by splinting) results in increased tremor in the distal segments. Under no-splinting conditions, significant relationships were only observed between adjacent (intra-limb) effector units, with the strength of the correlation increasing from proximal to distal. Splinting the right limb resulted in an increase in the strength and number of significant intra-limb relationships in both limbs. No inter-limb tremor relationships were found between any segment during this task, irrespective of the splinting condition. The frequency profile for the tremor in each limb segment showed two prominent frequency peaks (at 2-4 Hz and 8-12 Hz). A third, higher frequency peak (18-22 Hz) was observed in the index fingers only. Splinting the right limb produced a general increase in the amplitude and variability of tremor in the fingertip of both arms. This effect was particularly strong under conditions where the more proximal joints were splinted. The lack of any between-limb relationships, coupled with the fact that splinting one limb influenced both limbs, suggests that some form of linkage does exist between the limbs. It is unlikely that mechanical linkages can explain fully these relationships. It is proposed that the tremor observed in either limb represents the output of a central oscillatory mechanism(s), but that this output is subsequently independently filtered in a parallel fashion on its way to each respective limb. A common bilateral (compensatory) strategy is employed to minimize the tremor in either limb during this multiple-degrees-of-freedom task.     

The nature of essential tremor

The literature concerning essential tremor is confusing. Some accounts describe tremor of a resting type and its accompaniment by other neurological abnormalities. Critical analysis of the pertinent literature leaves some question as to the validity of these observations.Clinical analysis of 34 patients with essential tremor, personally observed during a four-year period, reveals this to be a monosymptomatic condition. The tremor was usually of both a postural and action type and resting tremor was not observed. There were no other neurological abnormalities. Serious disability was infrequent and, when present, was related to upper limb tremor. Essential tremor should be readily distinguishable from other central nervous system diseases but it may be confused with Parkinson''s disease or cerebellar ataxia.     

Effects of coupled upper limbs movements on postural stabilisation

The preference for in-phase association of coupled cyclic limbs movements is well described (mirror-symmetrical patterns) and this is demonstrated by the ease of performing in-phase movements compared to anti-phase ones. The hypothesis of this study is that the easiest movement patterns are those with minor postural activity. The aim of this study was to describe postural activity in standing subjects in the sagittal and frontal planes during the execution of three upper limbs tasks (single arm, in-phase, anti-phase) at four different frequencies (from 0.6 to 1.2 Hz).We employed six infrared cameras for recording kinematics information, a force platform for measuring forces exerted on the ground, and a system for surface electromyography (SEMG). Outcome measures were: upper limb range of movement and relative-phase, centre of pressure displacement (COP), screw torque (T_z) exerted on the ground, and SEMG recordings of postural muscles (adductor longus, gluteus medius, rectus femoris, and biceps femoris).Our results show that in both the planes the in-phase task resulted in less COP displacement, torque production, and postural muscles involvement than the anti-phase and single arm tasks. This reduced need of postural control could explain the ease of performing in-phase coupled limb movements compared with anti-phase movements.     

L-Dopa in Parkinsonism and the Influence of Previous Thalamotomy

A double-blind cross-over trial over 24 weeks (10 weeks on the active remedy, 4 weeks off treatment, and 10 weeks on placebo) of the effect of L-dopa on idiopathic Parkinsonism (paralysis agitans) has shown no difference in the response obtained in patients who had undergone previous stereotaxic ventrolateral thalamotomy and in those who had not. Of the 34 patients (18 men and 16 women) in the trial 18 had been operated on (nine unilateral, nine bilateral operations) and 16 had not. All patients entering the trial were taking anticholinergic drugs in stable dosage and these were continued throughout. The only factor which seemed to limit the response to treatment was pre-existing hypertension. Of 31 patients who completed the 10-week treatment period, 12 showed marked improvement, 15 moderate improvement, and 4 and mild or negligible change. It seems that previous ventrolateral thalamotomy affords some protection against the development of L-dopa-induced involuntary limb movements on the side contralateral to the operation. As found by others, maximum benefit was seen in bradykinesia and rigidity and related features but a significant reduction in tremor was also noted during treatment. Side effects (nausea, hypotension, and involuntary movements) were common but rarely limited the therapeutic response.     

Effect of Tetrabenazine on Extrapyramidal Movement Disorders

Thirty patients with various extrapyramidal movement disorders were treated for prolonged periods with 75 to 225 mg. daily of tetrabenazine. In patients with choreiform and hemiballistic motor activity the involuntary movements were diminished or abolished. In patients with cerebellar or Parkinsonian tremor the tremor was aggravated in moderately severe cases, but was uninfluenced in severe cases. In all cases the dyskinesia returned when- the drug was stopped.Side-effects were inconsiderable and disappeared on reducing the dose slightly. Hence the drug may be an important alternative to neurosurgical treatment of hyperkinesias and especially suitable for severely disabled patients.     

Characteristics of Gait Ataxia in δ2 Glutamate Receptor Mutant Mice,ho15J

The cerebellum plays a fundamental, but as yet poorly understood, role in the control of locomotion. Recently, mice with gene mutations or knockouts have been used to investigate various aspects of cerebellar function with regard to locomotion. Although many of the mutant mice exhibit severe gait ataxia, kinematic analyses of limb movements have been performed in only a few cases. Here, we investigated locomotion in ho15J mice that have a mutation of the δ2 glutamate receptor. The cerebellum of ho15J mice shows a severe reduction in the number of parallel fiber-Purkinje synapses compared with wild-type mice. Analysis of hindlimb kinematics during treadmill locomotion showed abnormal hindlimb movements characterized by excessive toe elevation during the swing phase, and by severe hyperflexion of the ankles in ho15J mice. The great trochanter heights in ho15J mice were lower than in wild-type mice throughout the step cycle. However, there were no significant differences in various temporal parameters between ho15J and wild-type mice. We suggest that dysfunction of the cerebellar neuronal circuits underlies the observed characteristic kinematic abnormality of hindlimb movements during locomotion of ho15J mice.     

Activation of interlimb interactions increases the motor output in legs of healthy subjects: Study under the conditions of arm and leg unloading

The effect of arm movements and movements of individual arm joints on the electrophysiological and kinematic characteristics of voluntary and vibration-triggered stepping-like leg movements was studied under the conditions of horizontal support of the upper and lower limbs. The horizontal support of arms provided a significant increase in the rate of activation of locomotor automatism by noninvasive impact on tonic sensory inputs. The addition of active arm movements during involuntary stepping-like leg movements led to an increase in the EMG activity of hip muscles and was accompanied by an increase in the amplitude of hip and shin movements. The movement of the shoulder joints led to an increase in the activity of hip muscles and was accompanied by an increase in the amplitude of hip and shin movements. Passive arm movements had the same effect on induced leg movements. The movement of the shoulder joints led to an increase in the activity of hip muscles and an increase in the amplitude of movements of knee and hip joints. At the same time, the movement of forearms and wrists had a similar facilitating effect on the physiological and kinematic characteristics of rhythmic stepping-like movements, but influenced the distal segments of legs to a greater extent. Under the conditions of subthreshold vibration of leg muscles, voluntary arm movements led to activation of involuntary rhythmic stepping movements. During voluntary leg movements, the addition of arm movements had a significantly smaller impact on the parameters of rhythmic stepping than during involuntary leg movements. Thus, the simultaneous movements of the upper and lower limbs are an effective method of activation of neural networks connecting the rhythm generators of arms and legs. Under the conditions of arm and leg unloading, the interactions between the cervical and lumbosacral segments of the spinal cord seem to play the major role in the impact of arm movements on the patterns of leg movements. The described methods of activation of interlimb interactions can be used in the rehabilitation of post-stroke patients and patients with spinal cord injuries, Parkinson’s disease, and other neurological diseases.     

Effect of a low intensity magnetic field on human motor behavior

Extremely low frequency (ELF) magnetic fields (MF) are omnipresent in our modern daily environment, but their effects on humans are still not clearly established. The aim of this study was to determine the effect of a 50 Hz, 1,000 microT MF centered at the level of the head on human index finger micro-displacements. Twenty-four men recruited among the personnel of the French company, Electricité de France (EDF), completed the experiment. Their postural and kinetic tremors were recorded under four "field-on" and four "field-off" conditions, each tested during a real and a sham sequence. Eight postural and four kinetic tremor characteristics were calculated on recorded time series and were used for statistical analysis. No effect of the MF was found for kinetic tremor. Concerning postural tremor, the proportion of oscillations at low frequencies (between 2 and 4 Hz) was higher during the real than during the sham exposure sequence (P<.05). It suggests that MF could have a subtle delayed effect on human behavior, which is clearly not pathological. These results should be taken into account for the establishment of new exposure limits.     

Organization of physiological tremors and coordination solutions to postural pointing on an uneven stance surface

The study investigated the destabilization effect on multi-segment physiological tremors and coordinative control for a postural-suprapostural task under different stance conditions. Twenty volunteers executed postural pointing from a level surface and a seesaw balance board; meanwhile, physiological tremors of the whole postural system and fluctuation movements of fingertip/stance surface were recorded. In reference to level stance, seesaw stance led to much fewer tremor increments of the upper limb and less fluctuation movement of the fingertip than tremor increment of the lower limb and rolling movement of the stance surface. Tremor coupling between the adjacent segments organized differentially with stance surface. In reference to level stance, seesaw stance reinforced tremor coupling of the upper limb but enfeebled the coupling in the arm-lumbar and calf-foot complexes. Stance-related differences in physiological tremors could be explained by characteristic changes in the primary and secondary principal components (PC1 and PC2), with relatively high communality with segment tremors of the lower and upper limbs, respectively. Seesaw stance introduced a prominent 4-8Hz spectral peak in PC1 and potentiated 1-4Hz and 8-12Hz spectral peaks of PC2. Structural reorganization of physiological tremors with stance configuration suggests that seesaw stance involves distinct suprapostural and postural synergies for regulating degree of freedom in joint space.     

The locus coeruleus is directly implicated in L-DOPA-induced dyskinesia in parkinsonian rats: an electrophysiological and behavioural study

Despite being the most effective treatment for Parkinson's disease, L-DOPA causes a development of dyskinetic movements in the majority of treated patients. L-DOPA-induced dyskinesia is attributed to a dysregulated dopamine transmission within the basal ganglia, but serotonergic and noradrenergic systems are believed to play an important modulatory role. In this study, we have addressed the role of the locus coeruleus nucleus (LC) in a rat model of L-DOPA-induced dyskinesia. Single-unit extracellular recordings in vivo and behavioural and immunohistochemical approaches were applied in rats rendered dyskinetic by the destruction of the nigrostriatal dopamine neurons followed by chronic treatment with L-DOPA. The results showed that L-DOPA treatment reversed the change induced by 6-hydroxydopamine lesions on LC neuronal activity. The severity of the abnormal involuntary movements induced by L-DOPA correlated with the basal firing parameters of LC neuronal activity. Systemic administration of the LC-selective noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine did not modify axial, limb, and orolingual dyskinesia, whereas chemical destruction of the LC with ibotenic acid significantly increased the abnormal involuntary movement scores. These results are the first to demonstrate altered LC neuronal activity in 6-OHDA lesioned rats treated with L-DOPA, and indicate that an intact noradrenergic system may limit the severity of this movement disorder.     

Basal ganglia oscillations and pathophysiology of movement disorders

Low frequency rest tremor is one of the cardinal signs of Parkinson's disease and some of its animal models. Current physiological studies and models of the basal ganglia differ as to which aspects of neuronal activity are crucial to the pathophysiology of Parkinson's disease. There is evidence that neural oscillations and synchronization play a central role in the generation of the disease. However, parkinsonian tremor is not strictly correlated with the synchronous oscillations in the basal ganglia networks. Rather, abnormal basal ganglia output enforces abnormal thalamo-cortical processing leading to akinesia, the main negative symptom of Parkinson's disease. Parkinsonian tremor has probably evolved as a downstream compensatory mechanism.     

Is There a Role for Combined EMG-fMRI in Exploring the Pathophysiology of Essential Tremor and Improving Functional Neurosurgery?

Background

Functional MRI combined with electromyography (EMG-fMRI) is a new technique to investigate the functional association of movement to brain activations. Thalamic stereotactic surgery is effective in reducing tremor. However, while some patients have satisfying benefit, others have only partial or temporary relief. This could be due to suboptimal targeting in some cases. By identifying tremor-related areas, EMG-fMRI could provide more insight into the pathophysiology of tremor and be potentially useful in refining surgical targeting.

Objective

Aim of the study was to evaluate whether EMG-fMRI could detect blood oxygen level dependent brain activations associated with tremor in patients with Essential Tremor. Second, we explored whether EMG-fMRI could improve the delineation of targets for stereotactic surgery.

Methods

Simultaneous EMG-fMRI was performed in six Essential Tremor patients with unilateral thalamotomy. EMG was recorded from the trembling arm (non-operated side) and from the contralateral arm (operated side). Protocols were designed to study brain activations related to voluntary muscle contractions and postural tremor.

Results

Analysis with the EMG regressor was able to show the association of voluntary movements with activity in the contralateral motor cortex and supplementary motor area, and ipsilateral cerebellum. The EMG tremor frequency regressor showed an association between tremor and activity in the ipsilateral cerebellum and contralateral thalamus. The activation spot in the thalamus varied across patients and did not correspond to the thalamic nucleus ventralis intermedius.

Conclusion

EMG-fMRI is potentially useful in detecting brain activations associated with tremor in patients with Essential Tremor. The technique must be further developed before being useful in supporting targeting for stereotactic surgery.     

Physiological tremor and control of limb position in 1 and 0 G

Muscle and skeletal mechanoreceptors play an important role for the regulation of muscular tone and the genesis of normal Physiological Tremor (PT). For example if a big limb as the arm or leg is kept against the gravity vector, the la afferent spindle discharges continuously control the load bearing flexor in a negative feedback manner in order to compensate the gravity vector and to the stabilize arm position. This servo-like action, denoted as 'stretch reflex', not only increases static postural stability (tonic stretch reflex) but also counteracts against external disturbances by dynamically increasing the muscle tone. Muscle spindles are very sophisticated sensory organs. They have an own innervation and the endings of the nuclear bag fibres are highly sensitive for small microstretches. EMG and microneurografic studies showed their importance in the mechanism of the 8-12 Hz component for PT. In a 0 G a limb becomes position controlled. In contrast to 1g, where control of limb position is a subordinated function of force compensation in the load bearing muscle, an antagonistic control scheme is necessary in 0 G to compensate the arm against positional drifts. As a consequence there is a shift from load dependent (muscular) to position dependent (skeletal) mechanoreceptors that become involved in the neural control process. As the control process is reflected in the tremor pattern, we investigated arm tremor in a constant limb position in 1 and 0 G.     

Effect of long-duration spaceflight on postural control during self-generated perturbations.

This report is the first systematic evaluation of the effects of prolonged weightlessness on the bipedal postural control processes during self-generated perturbations produced by voluntary upper limb movements. Spaceflight impacts humans in a variety of ways, one of which is compromised postflight postural control. We examined the neuromuscular activation characteristics and center of pressure (COP) motion associated with arm movement of eight subjects who experienced long-duration spaceflight (3--6 mo) aboard the Mir space station. Surface electromyography, arm acceleration, and COP motion were collected while astronauts performed rapid unilateral shoulder flexions before and after spaceflight. Subjects generally displayed compromised postural control after flight, as evidenced by modified COP peak-to-peak anterior-posterior and mediolateral excursion, and pathlength relative to preflight values. These changes were associated with disrupted neuromuscular activation characteristics, particularly after the completion of arm acceleration (i.e., when subjects were attempting to maintain upright posture in response to self-generated perturbations). These findings suggest that, although the subjects were able to assemble coordination modes that enabled them to generate rapid arm movements, the subtle control necessary to maintain bipedal equilibrium evident in their preflight performance is compromised after long-duration spaceflight.