Increased variability in spiral drawing in patients with functional (psychogenic) tremor

Increased variability is a characteristic clinical and physiologic feature of functional (psychogenic) tremor. In this study, we use computerized spiral analysis to show that the variability of a motor task is a quantifiable characteristic of functional tremor. We compare functional tremor patients to phenomenologically similar dystonic tremor patients and to normal controls. We used the spiral severity score, a measure that does not incorporate spiral tightness, as a marker of spiral drawing performance, and inter-spiral tightness variability (based on the 25–75%^ile range in tightness across ten spirals) to evaluate the effects of functional tremor on drawing spirals. The spirals of 74 participants: 22 functional tremor, 21 dystonic tremor, and 31 normal controls were analyzed. Spiral severity was higher in both tremor groups compared to controls, but did not differentiate them. Inter-spiral variability, however, was higher in the functional tremor group compared to both other groups. Thus, spiral analysis captures variability of a motor task and may be used as an objective test for functional tremor. The effect of functional tremor in other motor tasks should be investigated.     

Changes in the dynamics of tremor during goal-directed pointing.

For successful performance of activities requiring a fine level of manipulative control and dexterity, precise control over the intrinsic oscillations (tremor) in each segment is essential. However, the question of how individuals control (minimize) their tremor during precise postural movements remains unresolved. The aim of this study was to investigate the changes observed in limb tremor during goal-directed postural pointing tasks. Seven subjects attempted to minimize limb tremor during a pointing task whereby progressively greater levels of accuracy were required. Subjects held a small lightweight laser pointer in their extended hand during all tasks, the goal being to maintain the laser emission within a specified target area. Frequency analysis showed that the tremor profile for the hand and index finger was characterized by two prominent frequency peaks, located between 2-4 and 8-12 Hz. When the accuracy requirement of the task increased, there was a significant increase in the amplitude of the 8-12 Hz peak for all segments. Analysis of the time series component of tremor revealed a similar trend with the root mean square (RMS) and approximate entropy (ApEn) of the finger tremor increasing as the accuracy requirement increased. This same pattern was not seen for hand tremor where a small but systematic decrease in both the tremor RMS and ApEn was observed. Overall, it would appear that subjects attempted to reduce tremor at the finger by exerting greater control over the hand (as evidenced by decreased tremor output and increased regularity in the tremor signal). Unfortunately, the consequence of this strategy was that the tremor in the distal effector actually increased. Changes in the tremor output observed as a result of defining an explicit external goal probably resulted from the enhanced visual information provided by the laser emission. However, it would appear that subjects were not able to utilize this feedback effectively to reduce their tremor during the targeting tasks.     

Modulation of tremor amplitude during deep brain stimulation at different frequencies

Rest tremor was quantified in the index finger tip of 16 patients with Parkinson's disease (PD) receiving deep brain stimulation (DBS) of the ventro-intermediate nucleus (Vim) of the thalamus, the subthalamic nucleus (STN), or the internal part of the globus pallidus (GPi) while being off L-dopa for 12h. Clinically, without DBS, tremor amplitude varied from absent to high. Tremor was recorded continuously for about 5 min under three conditions of DBS repeated twice, namely, effective frequency (E), ineffective frequency (I), and no DBS (O). No changes in tremor were observed across conditions in subjects with little or no tremor. However, in subjects with moderate to large amplitude tremor, DBS decreased tremor amplitude to near normal values within a few seconds. Generally, transitions were progressive and occurred with a varying time delay. Occasionally, tremor escaped from control regardless of the stimulation condition considered. In some cases tremor amplitude in one condition appeared to depend on the preceding condition. Finally, the results were reproducible on two consecutive days. We conclude that tremor control with DBS follows specific dynamical rules, which must be compatible with the hypotheses proposed regarding the underlying mechanisms of DBS.     

Lessons learned in deep brain stimulation for movement and neuropsychiatric disorders

The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that "chronically" implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.     

Effect of Hand Posture on the Temporal and Kinematic Properties of Pointing and Drawing Movements Executed by Healthy Subjects and by a Patient With Primary Writing Tremor

Healthy individuals (n = 6) and a patient with "pure" primary writing tremor executed pointing and drawing movements while adopting different hand postures. The control subjects and the patient exhibited similar kinematics for most conditions. The patient displayed a severe right hand 4- to 6-Hz tremor and prolonged movements only when drawing with his normal hand posture. His tremor was manifested after a ready cue, in anticipation of a go command. The premovement tremor was abolished when the authors simply eliminated the ready cue and instructed the patient to relax and not think about drawing until he heard the go cue. Thus, the patient's writing tremor depended not only upon the writing or drawing act but also upon the hand position adopted and the intent to write, even in the absence of movement. The present results suggest that (a) similar high-level control mechanisms exist for pointing and drawing in healthy subjects and (b) the patient's deficits are compatible with a higher motor defect in central nervous system structures involved in the control of pointing and drawing movements.     

The neuropharmacology of beta adrenolytics

The paper provides a survey of neuropharmacological fundamentals for the use of beta-adrenolytics in the treatment of psychiatric and neurological diseases. In particular there are discussed results of animal- and clinical-pharmacological experiments carried out in order to assess the influence of betaadrenolytics in disorders and diseases such as anxiety, psychoses, tremor, some kinds of addiction, migraine and epilepsy. The conclusion is that in spite of some ascertained clinical indications on the one hand and a variety of neuropharmacological results on the other the mode of action of betaadrenolytics at the level of the CNS remains still insufficiently explainable.     

Quantification of manual force control and tremor

Isometric impulse frequencies associated with active tremor and force regulation were examined in 10 patients with idiopathic Parkinson's disease (PD) and in 10 older adults (OAs) who performed an isometric tracing task. The authors decoupled and analyzed the data to determine whether PD-related tremor in the thumb and in the index finger during isometric force control are related and whether PD impairs the performance of volitional force control beyond the errors contributed by tremor. After decoupling, there were clear and robust differences in PD patients' control of isometric force that could not be attributed to action-tremor error. Those errors, which occurred in the absence of movement, suggest impairment in coordinated recruitment and derecruitment of motor units during a fine-motor task.     

Methods of time and frequency domain examination of physiological tremor in the human jaw

This paper discusses, using the human jaw as a model, some of the commonly used techniques for examining physiological tremor. The EMG component driving mandibular physiological tremor approximately 7Hz can be revealed in the time domain manifestation of EMG by demodulation. The co-occurrence of approximately 7Hz physiological tremor (PT) in force and EMG can also be seen in the frequency domain representations of these signals and coherence analysis provides a method by which the degree of co-occurrence can be statistically investigated. Additionally, estimation of time lags between the signals by phase and cumulant density analysis provides evidence of the direction of dependence. Data presented herein using these techniques illustrates that for the human jaw, PT arises from a rhythmic component of EMG. This component is frequency and amplitude invariant across a range of bite forces indicating that it is not due to interaction between the stretch reflex and the mechanical resonance of the system.     

Interaction of Tremor and Magnification in a Motor Performance Task With Visual Feedback

In this study, the interaction between increased gain in the visual feedback loop and motor control of the periphery was investigated. Participants (N = 15) were asked to maintain a constant finger position while they used magnified visual feedback. The measure of the accuracy of each trial was the standard deviation (trial error) of the finger position. Trials performed under magnification had lower trial errors than trials without magnification. The change in trial error between trials with and without magnification proved greater than the difference between trials at any 2 magnifications. In contrast, the differences between individual subjects were often greater than the differences between performances at individual magnifications. At higher magnifications, performance seemed to be limited by the tremor; the ratio of trial error to tremor intensity was constant. When applied to microsurgery, the present results accord with those found in earlier research, including investigations that have found that the level of magnification used in microsurgery is not the most significant factor in achieving good results and that tremor is the limiting factor in microsurgical tasks.     

Assessing muscular fatigue with a portable tremor measurement system suitable for field use

The utility of a portable tremor measurement system for detecting muscle fatigue was evaluated. Static arm extension was used to induce fatigue. A probe containing two accelerometers, held in the extended hand, recorded horizontal and vertical tremor oscillations in the 1- to 18-Hz range. Several summary amplitude and frequency measures were then derived to analyze hand/arm tremor in the unfatigued and the fatigued states. Large increases from unfatigued to fatigued states were observed in all of the amplitude measures in both axes. Summary frequency measures were far less sensitive to fatigue. Correlations between consecutively measured observations revealed high levels of reliability (r τ .80) in all of the amplitude measures, but not in the frequency measures. The most robust index of fatigue was the total power in the entire 1- to 18-Hz spectrum. The other amplitude measures, however, are suitable for examining the effects of fatigue in isolated portions of the spectrum.     

Directional bias of limb tremor prior to voluntary movement

Taking a cue from recent discoveries of directional bias in microsaccades during visual fixation, we investigated directional bias in tremor during manual pointing. Subjects memorized and then performed patterns of alternating postures and voluntary movements. The directions of the tiny movements occurring during periods of intended stillness were predictive of subsequent target-directed movements such that in the horizontal axis, relative to baseline, the frequency of tremor decreased and the amplitude of tremor increased before horizontal movements, but not before vertical movements. This effect was less pronounced in the finger than in the arm, forearm, and hand. Possible explanations of the effect are based on eye-limb coupling, decreasing stiffness in the axis of forthcoming movement, and release of inhibition. The discovery of directionally specific preparatory activity suggests that the simple task of holding still before moving may provide a new window into the processes that allow for the translation of intentions into actions.     

Lithium tremor-combination treatment with beta receptor blockaders]

In addition to the various possibilities of influencing lithium tremor, experience gathered from the application of beta-receptor blockers is reported, and concepts investigated on the potential genesis and working mechanisms.     

The influence of motor system degradation on the control of handwriting movements: a dynamical systems analysis

The complex dynamics of the human hand/arm system need to be precisely controlled to produce fine movements such as those found in handwriting. This study employs dynamical systems analysis techniques to further understand how this system is controlled when it is functioning well and when it is compromised through motor function degradation (e.g. from tremor). Seven people with and 16 people without multiple sclerosis (MS) participated in this study. Tremor was assessed using spirography with participants being separated into "tremor" (6 people with and 1 person without MS; 2 male, 5 female; age range 40-68) and control (1 person with and 15 people without MS; 5 male, 11 female, age range 18-59) groups. Participants wrote the pseudo-word "lanordam" six times on a digitizer, in a quiet as well as a noisy, mildly stressful environment. Velocity profiles of the pen tip for the best four trials were concatenated and analyzed to determine their dimensionality (a measure of the number of control variables) and Lyapunov exponents (a measure of predictability). Results indicate that the velocity profiles for people with tremor were lower dimensional and had less predictable dynamics than for controls, with no effect of sound condition. Interpreted in the context of related research, it was speculated that the lower dimensionality reflected the loss of control of variables related to the minimization of movement variability, resulting in less predictable movements.     

A possible approach for discrimination between normal and pathological signals using the WFLC algorithm

The discrimination between normal and pathological tremor is difficult when amplitude is relatively small. The WFLC algorithm, a time domain adaptive Fourier transform, is designed to control physiological tremor and to improve precision during microsurgery. We added two iterative optimization processes to initialize the following parameters: initial frequency weight (omega0), amplitude adaptation rate (mu) and frequency adaptation rate (mu0). Then, we applied the methods on data sets recorded on patients with different tremors (control, parkinsonian, cerebellar, and essential) sampled at 200 Hz. After filtering the data, the WFLC algorithm tracked the time-varying dominant frequencies and amplitudes of the transformed data sets. Our results illustrate the potential of using this algorithm as an approach to discriminate between normal and pathological signals even when amplitude is not a significant discriminating factor.     

Neuromotor microalterations in subjects with spasmophilia symptoms: a preliminary study

Spasmophilia is a relatively unknown condition characterized by perturbations of the neuromuscular system. We hypothesized that spasmophilia may negatively affect neuromotor functions in subtle ways. Three tests including tremor, rapid pointing movements, and alternating movements were quantified in a group of subjects with spasmophilia symptoms (SS) (n = 10) and a healthy control group (n = 10). Most of the characteristics used to evaluate motor functions in these three tests revealed no significant differences between the two groups except for two characteristics in alternating movements and two characteristics in rapid pointing movements. In terms of variances, a dissociation between voluntary movements and involuntary movements was observed for the two groups. Control subjects had significantly higher variances in involuntary movements such as tremor, while subjects with SS had significantly higher variances in voluntary movements such as alternating and rapid pointing movements. A significant increase in asymmetry in hand laterality was also noted for some characteristics in subjects with SS.     

19世纪帕金森病的研究历史

1817年Parkinson首先描述了震颤麻痹,此后的45年中陆续出现了一些相关报道,但并未增加有价值的临床信息。1861年以后,Charcot对此病进行了深入的研究,认识到动作缓慢是本病的核心症状之一,并将其与肌强直鉴别开。他细致地描述了面具脸等症状,认为震颤并非诊断的必要因素,在命名上建议用帕金森病来取代震颤麻痹。     

Fragile X-associated tremor/ataxia syndrome (FXTAS)

Carriers of fragile X mental retardation 1 (FMR1) premutation alleles (55 to 200 CGG repeats) are generally spared the more serious neurodevelopmental problems associated with the full-mutation carriers (>200 repeats) of fragile X syndrome. However, some adult male premutation carriers (55-200 repeats) develop a neurological syndrome involving intention tremor, ataxia, dementia, parkinsonism, and autonomic dysfunction. In excess of one-third of male premutation carriers over 50 years of age develop the fragile X-associated tremor/ataxia syndrome (FXTAS). FXTAS also represents a new form of inclusion disease, with eosinophilic intranuclear inclusions found throughout the brain in both neurons and astrocytes. Because FXTAS appears to be relatively specific to male premutation carriers, who are known to possess elevated levels of FMR1 mRNA, the neuropathology may arise as a consequence of a toxic gain-of-function of the mRNA itself, although this proposal requires additional direct testing. One of the critical needs at present is a better estimate for the prevalence of this disorder, because FXTAS is likely to be underdiagnosed in the adult movement disorders clinics.     

Some evidence in support of a relationship between human auditory signal-detection performance and the phase of the alpha cycle

This study concerned the hypothesis presented by Lindsley in 1961 that human sensorimotor performance should vary with the phase of the alpha cycle. Although there have been a number of studies which have supported this hypothesis, there has been no work from a modality other than the visual modality. Since eye tremor is correlated in phase and frequency with the alpha rhythm, these visual results might be explained by the peripheral eye tremor and not necessarily by the central alpha rhythm. The present study measured human auditory signal-detection performance at four different phases of the temporally (T5-linked mastoids) measured alpha rhythm. These four different phases were defined on an a priori basis by a computer algorithm. Detection performance was significantly better at the negative peak of this alpha cycle than at the positive peak, but there was no significant difference between the positively and negatively going zero cross performances. These results are consistent with the Lindsley hypothesis.     

Complex oscillations in a human motor system

Experiments were performed to investigate the oscillations arising in a human motor system with delayed visual feedback. Eight subjects were instructed to maintain a constant finger position relative to a stationary baseline. The finger displacement was measured using a microdisplacement transducer connected to the index finger, and was displayed on an oscilloscope. Time delays between 40 and 1,500 ms were inserted in the visual feedback loop for 100 s. Results show that, as the time delays increase, irregular rhythms appear with short intermittent periods of regular oscillations. These regular low-frequency oscillations have an amplitude that increases with the time delays and a period that is consistently about 2 to 4 times the time delay. Fast Fourier Transforms (FFT) show a peak between 8 and 12 Hz, corresponding to physiological tremor in half the subjects. No systematic variations in the FFT for the 2 to 15 Hz range were observed as time delay increased. In the 0 to 2 Hz range, the FFT show a consistent increase in power with the time delay. These results indicate that, under the conditions of this experiment, tremor is not affected by time delays in the visuomotor system, and time delays in the visuomotor feedback loop give rise to complex oscillatory behaviors.     

A case of camptocormia (bent spine) secondary to early motor neuron disease

Camptocormia is a gait disorder, characterized by hyperflexion of thoracolumbar spine which increases on walking, and disappears in the supine position. A 48 year-old man developed progressive gait deterioration for one year and slight weakness and tremor of both hands for five months. It eventually became apparent that the patient had motor neuron disease, as well as symptoms of extrapyramidal disorder.