Using Portable Transducers to Measure Tremor Severity

Background: Portable motion transducers, suitable for measuring tremor, are now available at a reasonable cost. The use of these transducers requires knowledge of their limitations and data analysis. The purpose of this review is to provide a practical overview and example software for using portable motion transducers in the quantification of tremor. Methods: Medline was searched via PubMed.gov in December 2015 using the Boolean expression “tremor AND (accelerometer OR accelerometry OR gyroscope OR inertial measurement unit OR digitizing tablet OR transducer).” Abstracts of 419 papers dating back to 1964 were reviewed for relevant portable transducers and methods of tremor analysis, and 105 papers written in English were reviewed in detail. Results: Accelerometers, gyroscopes, and digitizing tablets are used most commonly, but few are sold for the purpose of measuring tremor. Consequently, most software for tremor analysis is developed by the user. Wearable transducers are capable of recording tremor continuously, in the absence of a clinician. Tremor amplitude, frequency, and occurrence (percentage of time with tremor) can be computed. Tremor amplitude and occurrence correlate strongly with clinical ratings of tremor severity. Discussion: Transducers provide measurements of tremor amplitude that are objective, precise, and valid, but the precision and accuracy of transducers are mitigated by natural variability in tremor amplitude. This variability is so great that the minimum detectable change in amplitude, exceeding random variability, is comparable for scales and transducers. Research is needed to determine the feasibility of detecting smaller change using averaged data from continuous long-term recordings with wearable transducers

Slow Orthostatic Tremor and the Case for Routine Electrophysiological Evaluation of All Tremors

In this issue of the journal, Hassan and Caviness reviewed the controversial topic of slow orthostatic tremor (OT). Based on their review of the relevant literature, Hassan and Caviness concluded that “multiple lines of evidence separate slow OT from classical OT,” but they also noted that “clinical and electrophysiologic overlap may occur.” We were invited to discuss the significance of this overlap within the context of tremor classification

CLCA2 Interactor EVA1 Is Required for Mammary Epithelial Cell Differentiation.

CLCA2 is a p53-, p63-inducible transmembrane protein that is frequently downregulated in breast cancer. It is induced during differentiation of human mammary epithelial cells, and its knockdown causes epithelial-to-mesenchymal transition (EMT). To determine how CLCA2 promotes epithelial differentiation, we searched for interactors using membrane dihybrid screening. We discovered a strong interaction with the cell junctional protein EVA1 (Epithelial V-like Antigen 1) and confirmed it by co-immunoprecipitation. Like CLCA2, EVA1 is a type I transmembrane protein that is regulated by p53 and p63. It is thought to mediate homophilic cell-cell adhesion in diverse epithelial tissues. We found that EVA1 is frequently downregulated in breast tumors and breast cancer cell lines, especially those of mesenchymal phenotype. Moreover, knockdown of EVA1 in immortalized human mammary epithelial cells (HMEC) caused EMT, implying that EVA1 is essential for epithelial differentiation. Both EVA1 and CLCA2 co-localized with E-cadherin at cell-cell junctions. The interacting domains were delimited by deletion analysis, revealing the site of interaction to be the transmembrane segment (TMS). The primary sequence of the CLCA2 TMS was found to be conserved in CLCA2 orthologs throughout mammals, suggesting that its interaction with EVA1 co-evolved with the mammary gland. A screen for other junctional interactors revealed that CLCA2 was involved in two different complexes, one with EVA1 and ZO-1, the other with beta catenin. Overexpression of CLCA2 caused downregulation of beta catenin and beta catenin-activated genes. Thus, CLCA2 links a junctional adhesion molecule to cytosolic signaling proteins that modulate proliferation and differentiation. These results may explain how attenuation of CLCA2 causes EMT and why CLCA2 and EVA1 are frequently downregulated in metastatic breast cancer cell lines

Real-Time Estimation of Pathological Tremor Parameters from Gyroscope Data

This paper presents a two stage algorithm for real-time estimation of instantaneous tremor parameters from gyroscope recordings. Gyroscopes possess the advantage of providing directly joint rotational speed, overcoming the limitations of traditional tremor recording based on accelerometers. The proposed algorithm first extracts tremor patterns from raw angular data, and afterwards estimates its instantaneous amplitude and frequency. Real-time separation of voluntary and tremorous motion relies on their different frequency contents, whereas tremor modelling is based on an adaptive LMS algorithm and a Kalman filter. Tremor parameters will be employed to drive a neuroprosthesis for tremor suppression based on biomechanical loading

Fatigue reduces the complexity of knee extensor torque during fatiguing sustained isometric contractions

The temporal structure, or complexity, of muscle torque output reflects the adaptability of motor control to changes in task demands. This complexity is reduced by neuromuscular fatigue during intermittent isometric contractions. We tested the hypothesis that sustained fatiguing isometric contractions would result in a similar loss of complexity. To that end, nine healthy participants performed, on separate days, sustained isometric contractions of the knee extensors at 20% MVC to task failure and at 100% MVC for 60 s. Torque and surface EMG signals were sampled continuously. Complexity and fractal scaling were quantified by calculating approximate entropy (ApEn) and the detrended fluctuation analysis (DFA) α scaling exponent. Global, central and peripheral fatigue were quantified using maximal voluntary contractions (MVCs) with femoral nerve stimulation. Fatigue reduced the complexity of both submaximal (ApEn from 1.02 ± 0.06 to 0.41 ± 0.04, P < 0.05) and maximal contractions (ApEn from 0.34 ± 0.05 to 0.26 ± 0.04, P < 0.05; DFA α from 1.41 ± 0.04 to 1.52 ± 0.03, P < 0.05). The losses of complexity were accompanied by significant global, central and peripheral fatigue (all P < 0.05). These results demonstrate that a fatigue-induced loss of torque complexity is evident not only during fatiguing intermittent isometric contractions, but also during sustained fatiguing contractions

Measuring movement fluency during the sit-to-walk task

Restoring movement fluency is a key focus for physical rehabilitation; it's measurement, however, lacks objectivity. The purpose of this study was to find whether measurable movement fluency variables differed between groups of adults with different movement abilities whilst performing the sit-to-walk (STW) movement. The movement fluency variables were: (1) hesitation during movement (reduction in forward velocity of the centre of mass; CoM), (2) coordination (percentage of temporal overlap of joint rotations) and (3) smoothness (number of inflections in the CoM jerk signal)

Two-cluster bifurcations in systems of globally pulse-coupled oscillators

For a system of globally pulse-coupled phase-oscillators, we derive conditions for stability of the completely synchronous state and all possible two-cluster states and explain how the different states are naturally connected via bifurcations. The coupling is modeled using the phase-response-curve (PRC), which measures the sensitivity of each oscillator's phase to perturbations. For large systems with a PRC, which turns to zero at the spiking threshold, we are able to find the parameter regions where multiple stable two-cluster states coexist and illustrate this by an example. In addition, we explain how a locally unstable one-cluster state may form an attractor together will its homoclinic connections. This leads to the phenomenon of intermittent, asymptotic synchronization with abating beats away from the perfect synchrony.Comment: 12 pages. 6 figure

Tremorgenesis: a new conceptual scheme using reciprocally innervated circuit of neurons

Neural circuits controlling fast movements are inherently unsteady as a result of their reciprocal innervation. This instability is enhanced by increased membrane excitability. Recent studies indicate that the loss of external inhibition is an important factor in the pathogenesis of several tremor disorders such as essential tremor, cerebellar kinetic tremor or parkinsonian tremor. Shaikh and colleagues propose a new conceptual scheme to analyze tremor disorders. Oscillations are simulated by changing the intrinsic membrane properties of burst neurons. The authors use a model neuron of Hodgkin-Huxley type with added hyperpolarization activated cation current (Ih), low threshold calcium current (It), and GABA/glycine mediated chloride currents. Post-inhibitory rebound is taken into account. The model includes a reciprocally innervated circuit of neurons projecting to pairs of agonist and antagonist muscles. A set of four burst neurons has been simulated: inhibitory agonist, inhibitory antagonist, excitatory agonist, and excitatory antagonist. The model fits well with the known anatomical organization of neural circuits for limb movements in premotor/motor areas, and, interestingly, this model does not require any structural modification in the anatomical organization or connectivity of the constituent neurons. The authors simulate essential tremor when Ih is increased. Membrane excitability is augmented by up-regulating Ih and It. A high level of congruence with the recordings made in patients exhibiting essential tremor is reached. These simulations support the hypothesis that increased membrane excitability in potentially unsteady circuits generate oscillations mimicking tremor disorders encountered in daily practice. This new approach opens new perspectives for both the understanding and the treatment of neurological tremor. It provides the rationale for decreasing membrane excitability by acting on a normal ion channel in a context of impaired external inhibition

Temporal discrimination is altered in patients with isolated asymmetric and jerky upper limb tremor

Background: Unilateral or very asymmetric upper limb tremors with a jerky appearance are poorly investigated. Their clinical classification is an unsolved problem because their classification as essential tremor versus dystonic tremor is uncertain. To avoid misclassification as essential tremor or premature classification as dystonic tremor, the term indeterminate tremor was suggested. Objectives: The aim of this study was to characterize this tremor subgroup electrophysiologically and evaluate whether diagnostically meaningful electrophysiological differences exist compared to patients with essential tremor and dystonic tremor. Methods: We enrolled 29 healthy subjects and 64 patients with tremor: 26 with dystonic tremor, 23 with essential tremor, and 15 patients with upper limb tremor resembling essential tremor but was unusually asymmetric and jerky (indeterminate tremor). We investigated the somatosensory temporal discrimination threshold, the short-interval intracortical inhibition, and the cortical plasticity by paired associative stimulation. Results: Somatosensory temporal discrimination threshold was significantly increased in patients with dystonic tremor and indeterminate tremor, but it was normal in the essential tremor patients and healthy controls. Significant differences in short-interval intracortical inhibition and paired associative stimulation were not found among the three patient groups and controls. Conclusion: These results indicate that indeterminate tremor, as defined in this study, shares electrophysiological similarities with dystonic tremor rather than essential tremor. Therefore, we propose that indeterminate tremor should be considered as a separate clinical entity from essential tremor and that it might be dystonic in nature. Somatosensory temporal discrimination appears to be a useful tool in tremor classification