Tremor Quantification Research Articles

Tremor analysis by decomposition of acceleration into gravity and inertial acceleration using inertial measurement unit

Decomposition of acceleration was investigated as an alternative to commonly used direct spectral analysis of measured acceleration or angular velocity for tremor quantification. An orientation estimation algorithm was devised to decompose the measured acceleration into the gravitational artifact and the inertial acceleration caused by sensor movement in an inertial reference frame. Resulting signals, beside the measured acceleration and angular velocity, were used to assess tremor amplitude and frequency by spectral peak detection. The algorithm was tested on experimental data from a clinical study including patients with essential tremor. The testing comprised of the classification of measurements to come from a patient or a healthy control and of the regression of the visual assessment of tremor amplitude. Small improvements in performance measures were achieved by using the decomposed acceleration. The regression accuracy was comparable to the accuracy achieved in other works. The influence of sensor calibration and connections of results to an analytic approach were analyzed briefly.

Spiralometry: Computerized assessment of tremor amplitude on the basis of spiral drawing

Spiral drawing has been used for the assessment of the impact of therapy on motor performance in various movement disorders (e.g. in Parkinson's disease, especially for tremor and hypokinesia). Nevertheless, there are only few guidelines available providing some kind of standardized interpretation. The published protocol with the highest standard is that of Bain and Findley. Kinetic tremor assessed by spiral drawing is not quantified by alternative approaches so far and is not even considered by most rating scales. However, kinetic tremor is quite common and represents a significant impairment in the everyday life of parkinsonian patients. More complex instrumental methods for the quantification of kinetic tremor have not been practical as they, e.g., require relatively expensive equipment or have an unfavourable effort/benefit ratio. We pursued an alternative approach, where we scan drawn spirals to a computer-algorithm that calculates the tremor amplitude. Our standardized method can be applied without difficulty in patients needing only paper and pencil. The evaluation is fully automated, and therefore, it is appropriate for the assessment of therapeutic efficacy in very large populations. The objectivity of the approach represents a significant advantage. In the actual paper, we present how we analyzed the original spirals published by Bain and Findley to validate our computerized assessment. We found a highly significant connection between both methods (explained variance: 88.9%).

Objective tremor registration during DBS surgery for Essential Tremor

Essential Tremor (ET) is characterized by a 4–12-Hz postural and kinetic tremor, most commonly affecting the upper limbs. Deep brain stimulation (DBS) of the thalamus (Vim) has been found to be highly effective in severe/refractory forms of ET. Intra-operative assessment of tremor is performed using clinical methods based on patient and physician perception of tremor intensity. We present for the first time the case of a patient whose tremor was objectively monitored/quantified pre- and intra-operatively using device-based tremor registration to supplement clinical measures. We present the case of a 76-year-old right-handed woman that received unilateral (left-sided) DBS of the ventrointermediate (Vim) nucleus of thalamus (Vim) for medically refractory ET. Tremor was monitored with an accelerometer-based Tremor Pen ®, which is part of a simple portable device (CATSYS 2000 System ®, Danish Product Development Ltd., DK, www.catsys.dk). The patient was asked to perform tasks for tremor evaluation before and during thalamic DBS. Tremor quantification revealed a significant improvement (34.7-fold) in the contralateral (right) limb following macro-stimulation. No significant improvement was registered in the ipsilateral (non-operated) side. Simple electronic tremor registration methods during DBS of the Vim nucleus of the thalamus may supplement the existing methodology that is solely based on subjective measures derived from clinical observations.

Spiral analysis: a new technique for measuring tremor with a digitizing tablet.

A new computational method for quantification of tremor and other aspects of motor dysfunction is described. By using a digitizing tablet connected to a microcomputer, this analysis is derived from the handwritten Archimedean spiral. This technique extends the standard clinical neurologic test of spiral drawing into an objective and accurate measure that can automatically detect, characterize, and quantify motor dysfunction in patients with movement disorders. Further, it is safe, inexpensive, fast, portable, noninvasive, and can be administered to a large cohort of patients without the need for wires or other attachments. Spiral data are collected in the X, Y, and pressure axes, providing virtual "triaxial" recordings. Spiral analysis is shown to be capable of assessing subtle motor abnormalities potentially indicative of clinical problems in their earliest stages, and thus allow the most rational forms of genetic testing, treatment, or prevention. Spiral analysis may be useful as an initial marker of clinical involvement or serve as an objective gauge of change after therapeutic intervention.

Quantification of Tremor and Bradykinesia in Parkinson's Disease Using a Novel Ambulatory Monitoring System

An ambulatory system for quantification of tremor and bradykinesia in patients with Parkinson's disease (PD) is presented. To record movements of the upper extremities, a sensing units which included miniature gyroscopes, has been fixed to each of the forearms. An algorithm to detect and quantify tremor and another algorithm to quantify bradykinesia have been proposed and validated. Two clinical studies have been performed. In the first study, 10 PD patients and 10 control subjects participated in a 45-min protocol of 17 typical daily activities. The algorithm for tremor detection showed an overall sensitivity of 99.5% and a specificity of 94.2% in comparison to a video reference. The estimated tremor amplitude showed a high correlation to the Unified Parkinson's Disease Rating Scale (UPDRS) tremor subscore (e.g., r = 0.87, p < 0.001 for the roll axis). There was a high and significant correlation between the estimated bradykinesia related parameters estimated for the whole period of measurement and respective UPDRS subscore (e.g., r = -0.83, p < 0.001 for the roll axis). In the second study, movements of upper extremities of 11 PD patients were recorded for periods of 3-5 hr. The patients were moving freely during the measurements. The effects of selection of window size used to calculate tremor and bradykinesia related parameters on the correlation between UPDRS and these parameters were studied. By selecting a window similar to the period of the first study, similar correlations were obtained. Moreover, one of the bradykinesia related parameters showed significant correlation (r = -0.74, p < 0.01) to UPDRS with window sizes as short as 5 min. Our study provides evidence that objective, accurate and simultaneous assessment of tremor and bradykinesia can be achieved in free moving PD patients during their daily activities.

Harmonics in frequency spectra: a contribution to differential diagnosis of tremor

Introduction: For quantification and differential diagnosis of tremor, electromyography (EMG) and accelerometry can be used supplementary to clinical assessment. Accelerometry essentially provides information regarding tremor amplitude and frequency. As there is a significant overlap in the frequencies of different tremor species, this parameter, however, is of limited value for specific diagnosis. EMG provides information about the patterns of agonistic and antagonistic muscle activity (alternating or co-contraction), but the specificity of this procedure is insufficient for individual diagnosis.

Validation of a new computerized system for recording and analysing drug-induced tremor in rats

Introduction: Certain drugs can induce tremor in small animals and can be used as Parkinson's disease or essential experimental tremor models. However, the use of arbitrary scales for evaluating tremor in experimental models is limited by observer subjectivity. Progress in electronics and computer science has allowed a more precise quantification of tremor. The objective of the present study was to validate a newly developed low-cost method of spectral registration and analysis of tremor in free-moving rats. Methods: Male Wistar rats, 3–4 months of age, previously placed for 5 min inside a sensor cage, were administered with different doses of eserine (0.25–1.5 mg/kg), oxotremorine (0.25–1.5 mg/kg) or harmaline (7.5–60 mg/kg). Drug-induced tremor was recorded during 10 min using a computerized system composed of force transducers, a signal conditioning circuit, a digitizing interface and a microcomputer. The signal transmitted to the computer was quantified, stored and analyzed for its amplitude and frequency by means of specific programs. Results: Tremor was induced with an amplitude that was dose-dependent for all drugs used. Tremor frequency was dose-dependent for oxotremorine and eserine, but not for harmaline. The performance of the system was compared with that of other systems described in behavioral instrumentation literature. Discussion: The present data indicate that the new system is capable of detecting the tremor induced by drugs, and that the programs used for spectral analysis allow the quantification of the amplitude and the frequency of the tremor in free-moving rats.

The application of video image processing to quantitative analysis of extremity tremor in humans

A new method for the detection and quantification of extremity tremor is described, based on video image processing. A single CCD camera recorded the movement of the extremity. A passive marker in the shape of a black annulus was placed on the forearm and the movement of the annulus analysed. The framestore digitised the video signal at a sample rate of 10 Hz. The time period of the movement analysis was Δ t=6.4 s. A total of 32 adults with alcoholism and 22 controls participated in this study. The movement of the extremity was recorded during the usual neurological test (sitting posture, feet together, upper extremities directly in front of subject) for both extremities. In this study, it was assumed that the probability density function f( d) of some variable D is characteristic of the tremor. This function is formed by a finite mixture of bivariate continuous distributions. The results suggest that f( d) characterises patients with alcoholism and distinguishes them from control subjects with only physiological tremor. The results demonstrate the capacity of the measuring system based on video imaging to quantifying motor impairments in clinical neurology.

Validity of long-term electromyography in the quantification of tremor.

We previously developed a method of tremor quantification using long-term electromyography registration of antagonistic forearm muscles that is reliable, sensitive, and specific for pathologic tremors. The present study demonstrates that tremor occurrence as measured by this method correlates well with clinical parameters of tremor in idiopathic Parkinson's disease (PD) and essential tremor (ET) (subscores of the Unified Parkinson's Disease Rating Scale for PD, tremor rating according to Bain et al. for ET). We conclude that the method is a valid and objective means of tremor quantification in PD and ET.

Adaptive Fourier modeling for quantification of tremor

A new computational method for quantification of tremor, the weighted frequency Fourier linear combiner (WFLC), is presented. This technique rapidly determines the frequency and amplitude of tremor by adjusting its filter weights according to a gradient search method. It provides continual tracking of frequency and amplitude modulations over the course of a test. By quantifying time-varying characteristics, the WFLC assists in correctly interpreting the results of spectral analysis, particularly for recordings exhibiting multiple spectral peaks. It therefore supplements spectral analysis, providing a more accurate picture of tremor than spectral analysis alone. The method has been incorporated into a desktop tremor measurement system to provide clinically useful analysis of tremor recorded during handwriting and drawing using a digitizing tablet. Simulated data clearly demonstrate tracking of variations in frequency and amplitude. Clinical recordings then show specific examples of quantification of time-varying aspects of tremor.

Quantification of essential tremor in writing and drawing.

Eighty-seven patients, aged 15-84 years (mean, 61.8 +/- 16.2 SD), with essential tremor wrote two series of cursive e's and cursive l's on a standard sheet of ruled paper that was mounted on a commercially available digitizing tablet. Forty patients also drew an Archimedes spiral. Postural wrist tremor was measured with a triaxial accelerometer on the dorsum of the horizontally extended hand. The digitizing tablet was sufficiently sensitive to measure sustained visible tremor. Very severe tremor could not be recorded when it prevented a patient from keeping the ballpoint pen on the tablet. The intertrial variability of the handwriting data was such that a 36.0% change in mean acceleration amplitude (cm/s2) and an 8.3% change in mean tremor frequency (Hz) could be detected in the hypothetical population of 30 patients (paired-sample t test, p = 0.01, power = 90%). The intertrial changes detectable with accelerometry were 35.9% (amplitude) and 7.8% (frequency). The correlations between wrist tremor and writing tremor were < 0.60 for amplitude and < 0.25 for frequency. Significant correlations between patient age and tremor frequency and between tremor amplitude and frequency existed for postural tremor but not for writing or drawing tremor. Standard digitizing tablets for personal computers are useful in the quantitative assessment of writing tremor. The amplitude and frequency characteristics of tremor in posture, writing, and drawing may differ significantly.

Modeling and canceling tremor in human-machine interfaces

Zero-phase modeling and canceling of tremor can improve precision in human-machine control applications. Past methods of tremor suppression have been hindered by feedback delays due to phase lag and by the inability to track tremor frequency over time. The weighted-frequency Fourier linear combiner (WFLC) is an adaptive noise canceller that precisely models tremor with zero phase lag. This article briefly presents the WFLC algorithm and describes its application to computer input filtering, clinical tremor quantification, and active tremor canceling for microsurgery.

Reliability, specificity and sensitivity of long-term tremor recordings

We have developed a method of long-term EMG recording that has proven suitable for the quantification of pathological tremor. In the present paper we show that the principal parameters of the method (tremor occurrence, tremor intensity, tremor frequency) are highly reproducible and that the method is specific and sensitive for detection of pathological tremor. Twelve patients with essential tremor (ET) and 13 patients with Parkinson's disease (PD) were recorded repeatedly on 3 successive days. For each patient group and for each parameter the intersubject variability was much larger than the intrasubject variability. The intraclass correlation coefficient “R” was in the order of 0.9 for each parameter and the mean of Pearson's correlation coefficient between successive days was also approximately 0.9. Recordings from normal controls demonstrated that the method's specificity for pathological tremor is 94.1% and its sensitivity is 96%.

Tremorlytic Activity of Budipine

The tremorlytic activity of the novel antiparkinson agent budipine was quantified in an open trial. Eleven patients with Parkinson's disease (PD) were treated with individual doses of budipine added to stable conventional antiparkinsonian medication. Tremor activity was measured using long-term electromyogram (EMG) recordings. Tremor intensity was reduced by 25%, tremor occurrence by 34%, and conventional "Unified Parkinson's Disease Rating Scale" (UPDRS) scores improved by 20% with this medication. There were two dropouts because of side effects. One dropout appeared not to be related to budipine. Apart from those, the drug was well tolerated by all patients. We conclude that budipine is an effective and well-tolerated tremorlytic drug and that the method of long-term EMG recording is suitable for tremor quantification in clinical studies.

Quantification of tremor with a digitizing tablet

Handwriting and drawing are commonly employed in the clinical assessment of tremor. These tasks have been quantified heretofore by subjective rating schemes, which are incapable of providing precise measures of the amplitude and frequency of tremor. A commercially-available digitizing tablet and personal computer can be interfaced so as to reliably record any pathologic tremor that is induced by writing or drawing. Numerical differentiation and spectral analysis can be used to conveniently quantify the amplitude and frequency of tremor. However, digitizing tablets lack sufficient sensitivity to measure physiologic tremor.

24 Hour continuous tremor quantification based on EMG recording

A new method is described that allows continuous quantification of parkinsonian and essential tremor over a period of up to 24 h on the basis of surface EMG recording from antagonistic forearm muscles. Tremor extraction from EMG data and all other calculations are performed on a digital computer. The occurrence, intensity and frequency of tremor are calculated. The data evaluation is fully automatic, including quality control and elimination of artifacts. Since tremor changes considerably over a 24 h period, long-term quantification gives more reliable data to study diurnal variations and to control the effects of medical treatment on tremor. As an additional advantage tremor recording is not restricted to a laboratory environment. Tremor can be monitored under everyday conditions and in the presence of moderate voluntary EMG activity.

24-Hour continuous tremor quantification based on EMG recordings: [formula omitted], E. Scholz and H.C. Diener (Dept. of Neurology, University of Tübingen, Tübingen, F.R.G.)

24-Hour continuous tremor quantification based on EMG recordings: [formula omitted], E. Scholz and H.C. Diener (Dept. of Neurology, University of Tübingen, Tübingen, F.R.G.)

Objective quantification of tremor in conscious unrestrained rats, exemplified with 5-hydroxytryptaminemediated tremor

To accomplish an objective quantification of tremor in conscious unrestrained rats, a registration device based on accelerometry was developed. Tremor intensity was continuously recorded by a small piezoresistive accelerometer (Egal 125-10D, Entran Devices) mounted on the back of the freely moving rat. The accelerometer was connected to a Grass Polygraph, where the analog signal was quantified as arbitrary sol| marks/ min by a 7P10 integrating unit. The integrated signals were then further analyzed by a desk-top computer (Luxor ABC-80). By analyzing tremor response to central serotonergic system activation, the reproducibility as well as the advantages and limitations of this recording system were demonstrated.

Further studies on quantification of drug-induced tremor in mice: Effects of antitremorgenic agents on tremor frequency

The effects of diazepam, dantrolene and atropine on drug-induced tremors were investigated in mice from the point of view of the tremor frequency. The study involved a power spectral analysis of the random current induced by movement of a magnet (attached to the mouse) on a wire coil. To induce tremor, tremorine and harmaline were subcutaneously injected. The power spectral density function defined the frequency composition of the tremor and its severity was determined quantitatively in terms of the mean square value of the data in any frequency range of concern. Diazepam markedly depressed the power spectral density of the tremorine- and harmaline-induced tremor and reduced the tremor frequency. With higher doses of diazepam, the peak frequency of the tremorine-induced tremor shifted to the lower frequency side as if the tremor components were taken into the component of the spontaneous motor activity. Dantrolene and atropine suppressed the power spectral density without affecting tremor frequency. The relationship between the change of tremor frequency and the site of action of antitremorgenic agents are discussed.

Quantification of tremor in rats induced by physostigmine.

A simple and accurate device for recording tremor intensity in unanaesthetized and unrestrained rats is described. The physical measures of tremor are shown to have several advantages over previous devices. First, the new apparatus, unlike some earlier ones, does not restrict the animal's movements to an unusually small cage, with weighty mechanical devices or with electrical leads. Second, most earlier methods for measuring tremor use a subjective rating scale. However, the present method uses objective and reliable measures. In a double-blind, illustrative experiment involving complete crossover, Wistar rats were randomly injected IP with physostigmine in doses of 0.2, 0.4, 0.6 and 0.8 mg/kg or the corresponding amount of 0.9% NaCl solution as control. The recorded tremor intensity showed a clear dose-response relationship for physostigmine. Moreover, linear regression of the dose-response relationship showed that tremor intensity increased linearly with increasing doses of physostigmine. The cholinergic antagonist atropine (0.3 mg/kg SC) antagonized physostigmine-induced tremor, whereas methylatropine (0.3 mg/kg SC) tended to potentiate it. These results show that the technique described is suitable for quantification of tremor intensity in rats and for testing drug interactions on physostigmine-induced tremor.