Tremor measurements in a 22-year cohort study of workers exposed to hand-held vibrating tools

Objectives The objectives of this cohort study were to evaluate possible long-term effects of occupational exposure to hand-arm vibration (HAV) in terms of increased tremor. The aims were to evaluate whether exposure during follow-up, baseline hand-arm vibration syndrome (HAVS), baseline manual dexterity or current medical conditions or life-style habits might be associated with increased tremor. A further aim was to compare two different activation conditions: postural vs rest tremor. Methods Forty men (current age: 60.4 years) who had previously worked as manual workers in a specialized engineering and construction company enrolled in the study. Their hand functions had been examined in 1994. At the baseline examination, 27 had been diagnosed with HAVS, while 13 were not exposed. The follow-up examination in 2016–2017 comprised the CATSYS Tremor Pen® for measuring postural and rest tremor and the Grooved Pegboard Test for assessing manual dexterity. Blood samples were taken for assessing biomarkers that might have impact on tremor. Results Neither cumulative exposure to HAV during follow-up nor HAVS at baseline were associated with increased tremor. A test for manual dexterity at baseline was significantly associated with increased tremor (Tremor Intensity) at follow-up. Blood markers of current medical conditions and tobacco consumption were associated with increased tremor. Rest tremor frequency was higher than postural tremor frequency (p < 0.001). Conclusions The main findings of this 22-year cohort study were no indications of long-term effects on tremor related to HAV exposure and previous HAVS status. However, baseline manual dexterity was significantly associated with increased tremor at follow-up. Activation conditions (e.g., hand position) are important when testing tremor.

Development and Validation of a New Wearable Mobile Device for the Automated Detection of Resting Tremor in Parkinson’s Disease and Essential Tremor

Involuntary tremor at rest is observed in patients with Parkinson’s disease (PD) or essential tremor (ET). Electromyography (EMG) studies have shown that phase displacement between antagonistic muscles at prevalent tremor frequency can accurately differentiate resting tremor in PD from that detected in ET. Currently, phase evaluation is qualitative in most cases. The aim of this study is to develop and validate a new mobile tool for the automated and quantitative characterization of phase displacement (resting tremor pattern) in ambulatory clinical settings. A new low-cost, wearable mobile device, called µEMG, is described, based on low-end instrumentation amplifiers and simple digital signal processing (DSP) capabilities. Measurements of resting tremor characteristics from this new device were compared with standard EMG. A good level of agreement was found in a sample of 21 subjects (14 PD patients with alternating resting tremor pattern and 7 ET patients with synchronous resting tremor pattern). Our results demonstrate that tremor analysis using µEMG is easy to perform and it can be used in routine clinical practice for the automated quantification of resting tremor patterns. Moreover, the measurement process is handy and operator-independent.

Algebraic estimator of Parkinson’s tremor frequency from biased and noisy sinusoidal signals

Tremor is an uncontrolled trembling movement or shakes, which are defined as an involuntary, rhythmic oscillatory movement of the body. The dominant features of Parkinsonism are the motor task and its frequency. This paper presents studies on the tremor parameter identification to be used for obtaining the frequency as a dynamical feature of the tremor. The method is based on the analysis of time-varying signals for identification of the tremor’s frequency from unknown noisy harmonic signals with an offset, using time-varying unstable filters and low-pass Butterworth filters. This approach uses an algebraic derivative method, in the frequency domain, to obtain the main frequency of tremors in the time domain. The first frequency mode of the tremor is one of the main characteristics to represent the low vibrational dynamics of Parkinson’s tremor. The proposed frequency estimation is performed in less than a period of the slower component of the measured signal. Real tremor signals were used to experimentally validate the proposed method and the algorithm proved to be fast and robust to high-frequency noises tracking the time variation of the tremor accurately.

Functional (Psychogenic) Movement Disorders

Functional movement disorders are any type of movement disorder due to a brain network disorder where normal function is possible. The terminology of functional movement disorders has changed; in the recent past, these disorders were most frequently called psychogenic. Characteristics of functional movements include incongruity with a known type of involuntary movement; inconsistency in the pattern, degree, and distribution during the clinical course; improvement with distraction; and possible psychogenic background. While the movements are said to be fully involuntary, there is often some suggestibility. In the case of unilaterally predominant tremor, if the patient is requested to repeat voluntary movements with the intact or less affected hand at a certain pace, the tremor frequency might be replaced by the frequency of the voluntary movement, the phenomenon called entrainment.

Voluntary and tremorogenic inputs to motor neuron pools of agonist/antagonist muscles in essential tremor patients

Pathological tremor is an oscillation of body parts at 3–10 Hz, determined by the output of spinal motor neurons (MNs), which receive synaptic inputs from supraspinal centers and muscle afferents. The behavior of spinal MNs during tremor is not well understood, especially in relation to the activation of the multiple muscles involved. Recent studies on patients with essential tremor have shown that antagonist MN pools receive shared input at the tremor frequency. In this study, we investigated the synaptic inputs related to tremor and voluntary movement, and their coordination across antagonist muscles. We analyzed the spike trains of motor units (MUs) identified from high-density surface electromyography from the forearm extensor and flexor muscles in 15 patients with essential tremor during postural tremor. The shared synaptic input was quantified by coherence and phase difference analysis of the spike trains. All pairs of spike trains in each muscle showed coherence peaks at the voluntary drive frequency (1–3 Hz, 0.2 ± 0.2, mean ± SD) and tremor frequency (3–10 Hz, 0.6 ± 0.3) and were synchronized with small phase differences (3.3 ± 25.2° and 3.9 ± 22.0° for the voluntary drive and tremor frequencies, respectively). The coherence between MN spike trains of antagonist muscle groups at the tremor frequency was significantly smaller than intramuscular coherence. We predominantly observed in-phase activation of MUs between agonist/antagonist muscles at the voluntary frequency band (0.6 ± 48.8°) and out-of-phase activation at the tremor frequency band (126.9 ± 75.6°). Thus MNs innervating agonist/antagonist muscles concurrently receive synaptic inputs with different phase shifts in the voluntary and tremor frequency bands. NEW & NOTEWORTHY Although the mechanical characteristics of tremor have been widely studied, the activation of the affected muscles is still poorly understood. We analyzed the behavior of motor units of pairs of antagonistic wrist muscle groups in patients with essential tremor and studied their activity at voluntary movement- and tremor-related frequencies. We found that the phase relation between inputs to antagonistic muscles is different at the voluntary and tremor frequency bands.

Role of cerebellar GABAergic dysfunctions in the origins of essential tremor

Essential tremor (ET) is among the most prevalent movement disorders, but its origins are elusive. The inferior olivary nucleus (ION) has been hypothesized as the prime generator of tremor because of the pacemaker properties of ION neurons, but structural and functional changes in ION are unlikely under ET. Abnormalities have instead been reported in the cerebello-thalamo-cortical network, including dysfunctions of the GABAergic projections from the cerebellar cortex to the dentate nucleus. It remains unclear, though, how tremor would relate to a dysfunction of cerebellar connectivity. To address this question, we built a computational model of the cortico-cerebello-thalamo-cortical loop. We simulated the effects of a progressive loss of GABAA α1-receptor subunits and up-regulation of α2/3-receptor subunits in the dentate nucleus, and correspondingly, we studied the evolution of the firing patterns along the loop. The model closely reproduced experimental evidence for each structure in the loop. It showed that an alteration of amplitudes and decay times of the GABAergic currents to the dentate nucleus can facilitate sustained oscillatory activity at tremor frequency throughout the network as well as a robust bursting activity in the thalamus, which is consistent with observations of thalamic tremor cells in ET patients. Tremor-related oscillations initiated in small neural populations and spread to a larger network as the synaptic dysfunction increased, while thalamic high-frequency stimulation suppressed tremor-related activity in thalamus but increased the oscillation frequency in the olivocerebellar loop. These results suggest a mechanism for tremor generation under cerebellar dysfunction, which may explain the origin of ET.

Modeling mechanisms of tremor reduction for essential tremor using symmetric biphasic DBS

Essential tremor (ET) is the most common movement disorder, in which the primary symptom is a prominent, involuntary 4–10 Hz movement. For severe, medication refractory cases, deep brain stimulation (DBS) targeting the ventral intermediate nucleus of the thalamus (VIM) can be an effective treatment for cessation of tremor and is thought to work in part by disrupting tremor frequency oscillations (TFOs) in VIM. However, DBS is not universally effective and may be further disrupting cerebellar-mediated activity in the VIM. Here, we applied biophysically detailed computational modeling to investigate whether the efficacy of DBS is affected by the mechanism of generation of TFOs or by the pattern of stimulation. We simulated the effects of DBS using standard, asymmetric pulses as well as biphasic, symmetric pulses to understand biophysical mechanisms of how DBS disrupts TFOs generated either extrinsically or intrinsically. The model results suggested that the efficacy of DBS in the VIM is affected by the mechanism of generation of TFOs. Symmetric biphasic DBS reduced TFOs more than standard DBS in both networks, and these effects were stronger in the intrinsic network. For intrinsic tremor frequency activity, symmetric biphasic DBS was more effective at reducing TFOs. Simulated non-tremor signals were also transmitted during symmetric biphasic DBS, suggesting that this type of DBS may help to reduce side effects caused by disruption of the cerebellothalamocortical pathway. Biophysical details in the model provided a mechanistic interpretation of the cellular and network dynamics contributing to these effects that can be empirically tested in future studies.Significance StatementEssential tremor (ET) is a common movement disorder, whose primary symptom is an involuntary rhythmic movement of the limbs or head. An area of the human tha-lamus demonstrates electrical activity that oscillates at the frequencies of tremor, and deep brain stimulation (DBS) in this area can reduce tremor. It is not fully understood how DBS affects tremor frequency activity in the thalamus, and studying different patterns of DBS stimulation may help to clarify these mechanisms. We created a computational model of different shapes of DBS and studied how they reduce different hypothesized generators of tremor frequency activity. A greater understanding of how DBS affects the thalamus may lead to improved treatments to reduce tremor and alleviate side effects in patients with ET.