Michael Lauk

Clinical neurophysiology of tremor.

The neurophysiological analysis of tremor has a long tradition. These attempts were directed to understand the mechanisms underlying tremor, on the one hand, and to develop tools to better diagnose the different types of tremor, on the other. Meanwhile, reasonable criteria are available to distinguish between centrally and peripherally mediated tremors. However, no generally accepted means exist to differentiate the different forms of central tremors. Frequency is a useful classifier for cerebellar tremor, rubral tremor, and orthostatic tremor. Although the highest amplitudes are found in Parkinsons disease, this parameter does not well distinguish between the different tremors. Waveform analysis of tremor is a promising tool to separate between the different tremors. Polymyography is pathognomonic for some rare forms of tremor. New approaches to classify tremors are based on positron emission tomography scanning, analysis of ballistic movement, and reflex testing. The means to separate myoclonias from tremors include EEG/EMG correlation techniques, long-latency reflexes, and polymyography. Provided these techniques are applied in the setting of careful clinical analysis of tremor syndromes, they may prove to be helpful in clinical practice.

Tremor-correlated cortical activity in essential tremor

BACKGROUND In patients with parkinsonian resting tremor, tremor-correlated activity in the contralateral sensorimotor cortex has been studied by both magnetoencephalography (MEG) and electroencephalography (EEG). In essential tremor, MEG failed to detect cortical involvement. The objective of this study was to investigate whether EEG recording can reveal tremor-correlated cortical activity in patients with essential tremor or enhanced physiological tremor. METHODS Seven patients with essential tremor and three patients with enhanced physiological tremor participated in the study. Unilateral postural tremor was activated by wrist extension on the right or on the left side. Electromyography (EMG) signals arising from the wrist extensor and flexor muscles, and a high-resolution EEG were recorded simultaneously. Coherences between the time series of the rectified tremor EMG and the EEG were estimated. FINDINGS In five of nine arms with essential tremor, we found highly significant coherences at the tremor frequency between the tremor EMG and the EEG. Isocoherence maps illustrating the topography of significant coherences over the scalp showed that the maximum coherences were located over the contralateral sensorimotor cortex. In the patients with enhanced physiological tremor, we were unable to detect consistent significant corticomuscular coherences at the tremor frequency. INTERPRETATION Using simultaneous EEG-EMG recordings, we showed that significant corticomuscular coherences at the tremor frequency can be found in essential tremor. This finding contrasts with a recent study based on MEG recordings. The results suggest that the sensorimotor cortex is involved in the generation of essential tremor, in a similar way to that previously shown in parkinsonian resting tremor.

Cross-spectral analysis of physiological tremor and muscle activity

Abstract We investigate the relationship between the extensor electromyogram (EMG) and tremor time series in physiological hand tremor by cross-spectral analysis. Special attention is directed to the phase spectrum and the effects of observational noise. We calculate the theoretical phase spectrum for a second-order linear stochastic process and compare the results to measured tremor data recorded from subjects who did not show a synchronized EMG activity in the corresponding extensor muscle. The results show that physiological tremor is well described by the proposed model and that the measured EMG represents a Newtonian force by which the muscle acts on the hand.

Cross-spectral analysis of physiological tremor and muscle activity II Application to synchronized electromyogram

Abstract We investigated the relationship between synchronized muscle activity and tremor time series in (enhanced) physiological tremor by cross-spectral analysis. Special attention was directed to the phase spectrum and its potential to clarify the contribution of reflex mechanisms to physiological tremor. The phase spectra are investigated assuming that the electromyogram (EMG) synchronization was caused by a reflex or a central oscillator. Comparing these results to phase spectra of measured data, we found a significant contribution of reflexes. But reflexes only modify existing peaks in the power spectrum. The main agents of physiological tremor are an efferent pace and the resonant behavior of the biomechanical system.

Tremor-correlated cortical activity detected by electroencephalography.

OBJECTIVE In this study we investigated whether cortical activity related to Parkinsonian resting tremor can be detected by electroencephalography (EEG). METHODS Seven patients with idiopathic Parkinsons disease suffering from unilateral tremor participated in the study. Electromyography (EMG) signals arising from the wrist extensor and flexor muscles as well as a high resolution EEG were recorded simultaneously. Coherencies between EEG and EMG were calculated. RESULTS In all patients, we found highly significant coherencies at the tremor frequency or its first harmonic between the tremor EMG and contralateral EEG channels. There were no significant coherencies between the tremor EMG and ipsilateral EEG channels. Isocoherency maps illustrating the topography of the coherencies over the scalp showed that the maximum coherencies were situated over the cortical motor areas. In one case, a high coherency was also found over the parietal cortex. CONCLUSIONS The results show for the first time that tremor-correlated cortical activity can be detected by electroencephalography. The findings underline that motor areas of the cerebral cortex are involved in the neuronal network generating resting tremor in Parkinsons disease.

CROSS-SPECTRAL ANALYSIS OF TREMOR TIME SERIES

We discuss cross-spectral analysis and report applications for the investigation of human tremors. For the physiological tremor in healthy subjects, the analysis enables to determine the resonant contribution to the oscillation and allows to test for a contribution of reflexes to this tremor. Comparing the analysis of the relation between the tremor of both hands in normal subjects and subjects with a rare abnormal organization of certain neural pathways proves the involvement of central structures in enhanced physiological tremor. The relation between the left and the right side of the body in pathological tremor shows a specific difference between orthostatic and all other forms of tremor. An investigation of EEG and tremor in patients suffering from Parkinsons disease reveals the tremor-correlated cortical activity. Finally, the general issue of interpreting the results of methods designed for the analysis of bivariate processes when applied to multivariate processes is considered. We discuss and apply partial cross-spectral analysis in the frame of graphical models as an extention of bivariate cross-spectral analysis for the multivariate case.

Quantitative analysis of tremor time series

Spectral analysis is applied to tremor time series in basic research and treatment monitoring. The estimation of the spectra from the data is usually done by averaging the squared modulus of the Fourier transform of segments of the data. We discuss drawbacks of this method and propose an alternative procedure to estimate the spectra adaptively based on the data. Thus, the method can be applied to all types of tremor. Applying the theory of spectral estimation, we propose a method to decide whether a spectrum exhibits multiple significant peaks and discuss different approaches to determine the amplitude of the tremor from the spectrum.

Essential tremor and cerebellar dysfunction: abnormal ballistic movements

Background: Clinical characteristics reminiscent of cerebellar tremor occur in patients with advanced essential tremor. Ballistic movements are known to be abnormal in cerebellar disease. The hypothesis was proposed that ballistic movements are abnormal in essential tremor, reflecting cerebellar dysfunction. Objective: To elucidate the role of the cerebellum in the pathophysiology of essential tremor. Methods: Kinematic parameters and the triphasic electromyographic (EMG) components of ballistic flexion elbow movements were analysed in patients assigned to the following groups: healthy controls (n = 14), pure essential postural tremor (ETPT; n = 17), and essential tremor with an additional intention tremor component (ETIT; n = 15). Results: The main findings were a delayed second agonist burst (AG2) and a relatively shortened deceleration phase compared with acceleration in both the essential tremor groups. These abnormalities were most pronounced in the ETIT group, which had additional prolongation of the first agonist burst (AG1) and a delayed antagonist burst (ANT). Conclusions: Abnormalities of the triphasic pattern and kinematic parameters are consistent with a disturbed cerebellar timing function in essential tremor. These abnormalities were most pronounced in the ETIT group. The cerebellar dysfunction in essential tremor could indicate a basic pathophysiological mechanism underlying this disorder. ETPT and ETIT may represent two expressions within a continuous spectrum of cerebellar dysfunction in relation to the timing of muscle activation during voluntary movements.

Side-to-side correlation of muscle activity in physiological and pathological human tremors

OBJECTIVE Many tremors occur always or often bilaterally. The question arises whether this could be explained by a common source or commonly transmitting pathways or by bilaterally represented, independent structures with the same oscillatory properties. A similar tremor frequency does not provide sufficient information to clarify this question. METHODS We analyze coherencies between surface electromyographies (EMG) to investigate if bilateral physiologic (PT), essential (ET), Parkinsonian (PD) and orthostatic (OT) tremors originate from a common source for both sides of the body. We show that commonly used techniques to test whether coherencies are significant could lead to false positive results for tremor EMGs. A new estimation procedure is proposed to test EMG tremor time series on their linear independence. We apply this test to bilateral tremors. RESULTS All measured EMG-pairs in OT (n = 7) were highly coherent between both sides with reproducible coherency values of up to 0.99. All other investigated tremors, i.e. PT and enhanced physiological tremors (EPT, n = 117), ET (n = 76) and PD resting and postural tremors (n = 70) do not show a significant side-to-side correlation. CONCLUSIONS This finding shows that the pathophysiologies of OT and other pathological tremors are definitely different. Either they have different origins or different kinds of transmitting pathways. The proposed method might also be used to investigate other electrophysiological data and is a helpful, easy to use investigation for a daily clinical routine.

The effects of stochastic galvanic vestibular stimulation on human postural sway

Abstract Galvanic vestibular stimulation serves to modulate the continuous firing level of the peripheral vestibular afferents. It has been shown that the application of sinusoidally varying, bipolar galvanic currents to the vestibular system can lead to sinusoidally varying postural sway. Our objective was to test the hypothesis that stochastic galvanic vestibular stimulation can lead to coherent stochastic postural sway. Bipolar binaural stochastic galvanic vestibular stimulation was applied to nine healthy young subjects. Three different stochastic vestibular stimulation signals, each with a different frequency content (0–1 Hz, 1–2 Hz, and 0–2 Hz), were used. The stimulation level (range 0.4–1.5 mA, peak to peak) was determined on an individual basis. Twenty 60-s trials were conducted on each subject – 15 stimulation trials (5 trials with each stimulation signal) and 5 control (no stimulation) trials. During the trials, subjects stood in a relaxed, upright position with their head facing forward. Postural sway was evaluated by using a force platform to measure the displacements of the center of pressure (COP) under each subject’s feet. Cross-spectral measures were used to quantify the relationship between the applied stimulus and the resulting COP time series. We found significant coherency between the stochastic vestibular stimulation signal and the resulting mediolateral COP time series in the majority of trials in 8 of the 9 subjects tested. The coherency results for each stimulation signal were reproducible from trial to trial, and the highest degree of coherency was found for the 1- to 2-Hz stochastic vestibular stimulation signal. In general, for the nine subjects tested, we did not find consistent significant coherency between the stochastic vestibular stimulation signals and the anteroposterior COP time series. This work demonstrates that, in subjects who are facing forward, bipolar binaural stochastic galvanic stimulation of the vestibular system leads to coherent stochastic mediolateral postural sway, but it does not lead to coherent stochastic anteroposterior postural sway. Our finding that the coherency was highest for the 1- to 2-Hz stochastic vestibular stimulation signal may be due to the intrinsic dynamics of the quasi-static postural control system. In particular, it may result from the effects of the vestibular stimulus simply being superimposed upon the quiet-standing COP displacements. By utilizing stochastic stimulation signals, we ensured that the subjects could not predict a change in the vestibular stimulus. Thus, our findings indicate that subjects can act as ”responders” to galvanic vestibular stimulation.