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Background and ObjectivesTo investigate the relationship between botulinum toxin type A (BoNT-A) administration, tremor amplitude, and modulation of intracortical excitability and sensorimotor processing using paired-pulse transcranial magnetic stimulation (pp-TMS) in patients with early, tremor-dominant Parkinson disease (PD).MethodsTwelve de novo (naive to anti-PD medications) and 7 l-dopa (optimized on levodopa) participants with PD with tremor affecting one arm were recruited. All participants received 4 serial BoNT-A treatments for tremor every 12 weeks and peak effect was assessed 6 weeks posttreatment, totaling 8 visits over 42 weeks. Injection measures were based on kinematic tremor analysis. Short interval intracortical inhibition (SICI), intracortical facilitation (ICF), long interval intracortical inhibition (LICI), and measures of sensorimotor interaction (short-latency afferent [SAI] and long-latency afferent [LAI] stimulation) were assessed in both hemispheres using pp-TMS paradigms at each time point. Linear mixed models analyzed the effect of each pp-TMS measure and tremor severity within each cohort and the association between pp-TMS and tremor severity in the de novo cohort over 42 weeks. t Tests compared pp-TMS measures between hemispheres per time point.ResultsBaseline SICI, LICI, and SAI was reduced (higher motor evoked potential [MEP] ratio) on the tremulous/treated side compared to the nontremulous side in de novo participants. On the treated side in the de novo cohort, BoNT-A treatment significantly reduced ICF and increased LICI, SAI, and LAI (lower MEP ratio) at peak BoNT-A time points. The change in tremor severity was significantly associated with changes in SICI, LICI, and LAI.DiscussionOur findings suggest that tremor severity in early PD may be related to impaired intracortical inhibition and defective sensorimotor integration.

BackgroundTremor is a common and burdensome symptom in patients with dystonia, which is clinically heterogeneous and often resistant to treatment. The pathophysiology is suggested to involve abnormal activity in the cerebellum and motor cortex, but the causal role of these brain regions remains to be established. Transcranial alternating current stimulaton (TACS) can suppress rhytmic cerebral activity in other tremor disorders when phase-locked to the ongoing arm tremor, but the effect on dystonic tremor syndromes is unknown.Objective/HypothesisWe aimed to establish the causal role of the cerebellum and motor cortex in dystonic tremor syndromes, and explore the therapeutic efficacy of phase-locked TACS.MethodsWe applied phase-locked TACS over the ipsilateral cerebellum (N=14) and contralateral motor cortex (N=17) in dystonic tremor syndrome patients, while patients assumed a tremor-evoking posture. We measured tremor power using accelerometery during 30s stimulation periods at 10 different phase-lags (36-degrees increments) between tremor and TACS for each target. Post-hoc, TACS-effects were related to a key clinical feature: the jerkiness (regularity) of tremor.ResultsCerebellar TACS modulated tremor amplitude in a phase-dependent manner, such that tremor amplitude was suppressed or enhanced at opposite sides of the phase-cycle. This effect was specific for patients with non-jerky (sinusoidal) tremor (n=10), but absent in patients with jerky (irregular) tremor (n=4). Phase-locked stimulation over the motor cortex did not modulate tremor amplitude.ConclusionsThis study indicates that the cerebellum plays a causal role in the generation of (non-jerky) dystonic tremor syndrome. Our findings suggest pathophysiologic heterogeneity between patients with dystonic tremor syndrome, which mirrors clinical variability.

Background Assessment of essential tremor is often done by a trained clinician who observes the limbs during different postures and actions and subsequently rates the tremor. While this method has been shown to be reliable, the inter- and intra-rater reliability and need for training can make the use of this method for symptom progression difficult. Many limitations of clinical rating scales can potentially be overcome by using inertial sensors, but to date many algorithms designed to quantify tremor have key limitations. Methods We propose a novel algorithm to characterize tremor using inertial sensors. It uses a two-stage approach that 1) estimates the tremor frequency of a subject and only quantifies tremor near that range; 2) estimates the tremor amplitude as the portion of signal power above baseline activity during recording, allowing tremor estimation even in the presence of other activity; and 3) estimates tremor amplitude in physical units of translation (cm) and rotation (°), consistent with current tremor rating scales. We validated the algorithm technically using a robotic arm and clinically by comparing algorithm output with data reported by a trained clinician administering a tremor rating scale to a cohort of essential tremor patients. Results Technical validation demonstrated rotational amplitude accuracy better than ±0.2 degrees and position amplitude accuracy better than ±0.1 cm. Clinical validation revealed that both rotation and position components were significantly correlated with tremor rating scale scores. Conclusion We demonstrate that our algorithm can quantify tremor accurately even in the presence of other activities, perhaps providing a step forward for at-home monitoring.

OBJECTIVE: This study addresses an important problem in neurology, distinguishing tremor and ataxia using quantitative methods. Specifically, we aimed to quantitatively separate dysmetria, a cardinal sign of ataxia, from tremor in essential tremor (ET). METHODS: In Experiment 1, we compared 19 participants diagnosed with ET undergoing thalamic deep brain stimulation (DBS; ET(DBS)) to 19 healthy controls (HC). We quantified tremor during postural tasks using accelerometry and dysmetria with fast, reverse-at-target goal-directed movements. To ensure that endpoint accuracy was unaffected by tremor, we quantified dysmetria in selected trials manifesting a smooth trajectory to the endpoint. Finally, we manipulated tremor amplitude by switching DBS ON and OFF to examine its effect on dysmetria. In Experiment 2, we compared 10 ET participants with 10 HC to determine whether we could identify and distinguish dysmetria from tremor in non-DBS ET. RESULTS: Three findings suggest that we can quantify dysmetria independently of tremor in ET. First, ET(DBS) and ET exhibited greater dysmetria than HC and dysmetria did not correlate with tremor (R(2) < 0.01). Second, even for trials with tremor-free trajectories to the target, ET exhibited greater dysmetria than HC (p < 0.01). Third, activating DBS reduced tremor (p < 0.01) but had no effect on dysmetria (p > 0.2). INTERPRETATION: We demonstrate that dysmetria can be quantified independently of tremor using fast, reverse-at-target goal-directed movements. These results have important implications for the understanding of ET and other cerebellar and tremor disorders. Future research should examine the neurophysiological mechanisms underlying each symptom and characterize their independent contribution to disability.

BackgroundTremor is a cardinal symptom of Parkinson’s disease (PD) that may cause severe disability. As such, objective methods to determine the exact characteristics of the tremor may improve the evaluation of therapy. This methodology study aims to validate the utility of two objective technical methods of recording Parkinsonian tremor and evaluate their ability to determine the effects of Deep Brain Stimulation (DBS) of the subthalamic nucleus and of vision.MethodsWe studied 10 patients with idiopathic PD, who were responsive toL-Dopa and had more than 1 year use of bilateral subthalamic nucleus stimulation. The patients did not have to display visible tremor to be included in the study. Tremor was recorded with two objective methods, a force platform and a 3 dimensional (3D) motion capture system that tracked movements in four key proximal sections of the body (knee, hip, shoulder and head). They were assessed after an overnight withdrawal of anti-PD medications with DBS ON and OFF and with eyes open and closed during unperturbed and perturbed stance with randomized calf vibration, using a randomized test order design.ResultsTremor was detected with the Unified Parkinson’s Disease Rating Scale (UPDRS) in 6 of 10 patients but only distally (hands and feet) with DBS OFF. With the force platform and the 3D motion capture system, tremor was detected in 6 of 10 and 7 of 10 patients respectively, mostly in DBS OFF but also with DBS ON in some patients. The 3D motion capture system revealed that more than one body section was usually affected by tremor and that the tremor amplitude was non-uniform, but the frequency almost identical, across sites. DBS reduced tremor amplitude non-uniformly across the body. Visual input mostly reduced tremor amplitude with DBS ON.ConclusionsTechnical recording methods offer objective and sensitive detection of tremor that provide detailed characteristics such as peak amplitude, frequency and distribution pattern, and thus, provide information that can guide the optimization of treatments. Both methods detected the effects of DBS and visual input but the 3D motion system was more versatile in that it could detail the presence and properties of tremor at individual body sections.

Physiological tremor amplitude was studied along with the possibility of its biofeedback guided modification. Physiological tremor was recorded using three-axial digital accelerometers fixed on the external side of the index fingers. Subjects were asked to perform a series of 15-s physiological tremor tests with breaks to rest. Four biofeedback modes were used to minimize the following control parameters: hand inclination from a horizontal plane, mean tremor amplitude over both hands, tremor amplitude of the right hand with simulated left hand one, and inverse combination. The tremor amplitudes obtained in biofeedback conditions were compared to normal values, which were recorded before and after biofeedback testing. The possibility of targeted physiological tremor modification in a 8–12 Hz frequency band was proved by the suppression of tremor amplitude in biofeedback conditions. A transition of the tremor suppression effect in the band 8–12 Hz was observed; i.e., the tremor amplitude from the dominant arm significantly decreased when biofeedback parameters were obtained from the contralateral arm.

Background: Essential tremor (ET) occurs with steeply increasing prevalence in the elderly, and apart from disease duration, age is independently associated with an increase of tremor amplitude and a decrease of frequency. White matter hyperintensities (WMHs) are a common finding in the elderly, and their role in the pathophysiology of ET is unknown. The aims of this study were to examine whether ET patients differ in their total or region-specific WMH volumes from healthy controls and to determine the impact of WMH on tremor characteristics.Methods: A total of 47 elderly ET patients with a mean age of 72 years and 39 age-matched healthy controls underwent a thorough clinical assessment and 3T MRI. Total WMH volumes were derived from T2-weighted fluid-attenuated inversion recovery (FLAIR) MR images. Additionally, region of interest-based WMH volumes for the Johns Hopkins University (JHU) white matter tracts and labels were calculated, and WMHs were assessed semiquantitatively using the Fazekas scale.Results: Essential tremor patients and healthy controls did not differ in their total or tract-specific WMH volumes or Fazekas scores. However, WMH volume was significantly positively correlated with tremor severity on the TETRAS scale, and there was a significant negative correlation with the mean accelerometric tremor frequency. In a multiple linear regression model including disease duration, age, and age-adjusted total WMH volume, only the WMH volume significantly predicted tremor severity, while age and disease duration were not significant.Conclusion: We found evidence for a direct association between WMH volume and tremor severity. If confirmed by larger studies, our findings could explain the well-known relation between age and tremor severity.

Introduction Re-emergent tremor (RET) is a common form of postural tremor observed in Parkinson's disease (PD) patients. Recent studies have shown that administration of levodopa decreases RET amplitude. However, drug effects on tremor pause duration are less clear. Methods We performed a prospective observational study in PD patients with RET, subjected to acute levodopa challenge. Tremor activity was measured during OFF and ON states both clinically, as well as by using accelerometers taped to the back of both hands. Correlation between RET amplitude and pause duration, as well with MDS-UPDRS scores were investigated. The slope of gradual increase of postural tremor after the pause was also measured in the OFF and ON states. Results Significant inverse correlation between tremor amplitude and RET pause duration was observed in OFF (rs = −0.474, p = 0.030) and ON (rs = −0.569, p = 0.006) states. Levodopa reduced tremor amplitude (26%, p = 0.004) dampening slope gradient (22%, p = 0.029). Tremor pause duration also showed inverse correlation with postural tremor amplitude measured by MDS-UPDRS in OFF (rs = −0.311, p = 0.048) and ON (rs = −0.503, p = 0.020) states, as well as with total MDS-UPDRS Part III score (rs = −0.295, p = 0.009). Finally, accelerometric analysis proved to be more sensitive than visual inspection for detecting tremor pauses. Conclusion Our results suggest RET pause duration is amplitude related, since levodopa-induced amplitude decrease led to pause prolongation, associated with decreased tremor intensity and slope gradient dampening.

Background Primary orthostatic tremor (POT) is a rare disorder, characterized by 13 to 18 Hz tremor in the legs when standing and is often refractory to medical treatment. Epidural spinal cord stimulation has been proposed as an alternative treatment. However, this approach is invasive, which limits its application. Objective Trans-spinal direct current stimulation (tsDCS) is a non-invasive method to modulate spinal cord circuits. The aim of this proof-of-concept study was to investigate the potential beneficial effect of tsDCS in POT. Methods We conducted a double-blind, sham-controlled study in 16 patients with POT. In two separate visits, patients received sham tsDCS first followed by active (either cathodal or anodal) tsDCS. The primary outcome was the change in time in standing position. Secondary outcomes comprised quantitative assessment of tremor, measurement of corticospinal excitability including short-latency afferent inhibition, and clinical global impression-improvement (CGI-I). Measurements were made at baseline, after sham tsDCS, 0-30 min, and 30-60 min after active conditions. Results Cathodal-tsDCS reduced tremor amplitude and frequency and lowered corticospinal excitability whereas anodal-tsDCS reduced tremor frequency only. CGI-I scores positively correlated with the time in standing position after both active tsDCS conditions. Conclusion A single session of tsDCS can improve instability in POT. This opens a new vista for experimental treatment options using multiple sessions of spinal DC stimulation. © 2021 International Parkinson and Movement Disorder Society.

Continuous monitoring of tremor with wearable wrist sensors during normal daily activities is more difficult than in a clinical setting when subjects perform prescribed activities because some normal daily activities resemble tremor, many normal movements contain frequency content that overlaps with the tremor frequency, and the tremor amplitude has a large dynamic range during normal daily activities. We describe a novel two-stage algorithm that offers improvement at discriminating tremor from other activities. Some of this improvement is attained by using prior domain knowledge that tremor occurs over a narrow range of frequencies for an individual, but the mean tremor frequency may vary significantly between individuals in a study population. We validated the algorithm in continuous recordings from people with Parkinson’s disease and matched control subjects. The algorithm has good face validity, a low rate of false positives on recordings from control subjects (< 1.1%), and good correspondence with the constancy of rest tremor as measured by this question on the MDS-UPDRS (ρ = 0.54).

Limb tremor measurements are one factor used to characterize and quantify the severity of neurodegenerative disorders. These tremor measurements can also provide dosage-response feedback to guide medication treatments. Here, we propose a system to automatically measure limb tremors in home or clinic settings. The key feature of proposed method is that it is contactless; not requiring a user to wear or hold a device or marker. Our sensor is a Kinect 2, which measures color and depth and estimates rough limb motion. We show that its pose accuracy is poor for small limb tremors below 10 mm amplitude, and so we propose an additional level of tremor tracking that recovers limb motion at a higher precision. Our method upgrades the sensitivity to achieve detection and analysis for tremors down to 2 mm amplitude. We include empirical experiments and measurements showing improved tremor amplitude and frequency estimation using our proposed Pose and Optical Flow Fusion (POFF) algorithm. (c) 2020 Nalecz Institute of Biocybernetics and Biomedical Engineering of the Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

BACKGROUND Direct targeting of the dentato-rubro-thalamic tract is efficacious in DBS for tremor suppression. OBJECTIVES We sought to compare outcomes and optimal stimulation parameters for tremor control using the technique of directly targeting the dentato-rubro-thalamic tract to those who underwent indirect targeting of the ventral intermediate nucleus thalamus. METHODS Twenty consecutive essential tremor patients obtained preoperative diffusion MRIs, where the dentato-rubro-thalamic tract was individually drawn and used to directly target the ventral intermediate nucleus of the thalamus during surgery. These patients were compared to an earlier cohort of 20 consecutive patients who underwent surgery using atlas-based coordinates. Baseline and 1-year postsurgery tremor amplitude using The Essential Tremor Rating Assessment Scale was recorded, as were the parameters needed for successful tremor control. RESULTS The indirectly targeted group had greater baseline and postop tremor severity relative to those directly targeted (baseline, 2.9 vs. 2.6; P = 0.02; postop, 1.1 vs. 0.8; P = 0.03). Mean voltage, pulse width, and frequency for optimal tremor control in the directly targeted group (38 electrodes) = 2.8 V, 80 μs, 153 Hz; the parameters for the indirectly targeted group (38 electrodes) = 2.9 V, 86 µs, 179 Hz (significantly greater, P

Background: To present the current knowledge on the characteristics, assessment, and treatment of upper limb intention tremor to inform and improve future intervention studies in patients with multiple sclerosis (MS), we conducted a literature review for articles on upper limb intention tremor in patients with MS. Methods: Two reviewers conducted searches in PubMed, Web of Science, and MEDLINE (Ovid). Relevant articles, sorted on inclusion criteria, were examined for descriptions and assessments of upper limb intention tremor, and intervention studies were evaluated based on treatment type. Results: Eight descriptive studies were found reporting on the incidence and severity of tremor, impairments, and lesion load. Ten studies focused on measurement of tremor using various assessments. Intervention studies included eight articles using a diverse set of noninvasive techniques mainly showing transient reduction in tremor amplitude and temporary increase in function. Eighteen studies on pharmacologic interventions were found, with most displaying positive outcomes and mediation of tremor; others showed little to no benefit. Surgical interventions included 17 studies on thalamotomy and 20 on deep brain stimulation. Most studies showed tremor improvement after surgery; however, most sample sizes were small, and interventions were highly invasive, with potential adverse effects resulting from surgery. Conclusions: The literature on upper limb intention tremor in MS is relatively sparse. More studies are required to determine mechanism of action and to provide more suitable and sustainable interventions to decrease upper limb intention tremor and improve quality of life of individuals with MS.

Volcanic tremor is often observed to be associated with an increase in volcanic activity and during periods approaching eruptions. It is therefore of crucial importance to study this phenomenon. The opening of a new vent and subsequent ash–gas emissions was observed in the active crater (Nakadake crater) of Aso volcano, Japan, in January 2014. These events were considered to be associated with phreatomagmatic activity similar to the small events of 2003–2005. During the period from December 2013 to January 2014, a significant variation in the amplitude of continuous seismic tremors was observed corresponding to surficial volcanic activity. We estimated the tremor source locations for this two-month period by a three-dimensional grid search using the tremor amplitude ratio of 5–10 Hz band-pass filtered waveforms. The estimated source locations were distributed in a roughly cylindrical region (100–150 m in diameter) ranging from the ground surface to a depth of 400 m. Migration of the estimated source location was also identified and was associated with changes in volcanic activity. We assumed that the source locations coincided with a conduit system of the volcano, consisting of networks of fractures. This area is likely situated above the crack-like conduit proposed in previous studies. Before the 2014 event, an increase in gas-dominated volcanic fluid first caused an enlargement of the conduit zone, followed by the migration of further magmatic fluid through other pathways, which resulted in a subsequent ash–gas emission. Although we do not have sufficient information to discuss the causal relationship between these processes, it seems reasonable that continuous tremors might change the conduit conditions.

The paper deals with mathematical modeling tools for tremor quantification, a problem arising in e.g. clinical applications and sports. Tremor is an involuntary repetitive movement of extremities, head, or trunk that occurs in disease but also in health, due to e.g. strain or fatigue. Quantification of tremor is traditionally performed by ocular observation, while numerous technologies based on wearable accelerometer data exist and have been tested in medical practice. The currently available approaches rely on spectral analysis that reduces a fundamentally nonlinear and non-stationary phenomenon to a linear combination of harmonic components. The classical nonlinear identification methods are as well of limited use because the underlying system is essentially autonomous and produces sustained oscillations without exogenous excitation. An alternative view on tremor is therefore adopted that treats the problem from a severity rating perspective aligned with clinical practices. The tremor amplitude is modelled by a Markov chain, where the states represent the predefined intervals of severity. A comparison with a previously developed event-based method of tremor quantification is provided on data collected using a smart phone in a patient diagnosed with Parkinson disease and undergoing Deep Brain Stimulation therapy. The experimental procedure is unobtrusive and can be implemented in a way that is transparent to the patient.

The dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum. Yet the mechanisms by which these regions relate to tremor remain a matter of considerable debate. We sought to discriminate the contributions of cerebral and cerebellar dysregulation by combining high-density electroencephalography with subject-specific structural MRI. For that, we contrasted ET with voluntary (mimicked) tremor before and after ingestion of alcohol to regulate the tremorgenic networks. Our results demonstrate distinct loci of cortical tremor coherence, most pronounced over the sensorimotor cortices in healthy controls, but more frontal motor areas in ET-patients consistent with a heightened involvement of the supplementary motor area. We further demonstrate that the reduction in tremor amplitude associated with alcohol intake is reflected in altered cerebellar - but not cerebral - coupling with movement. Taken together, these findings implicate tremor emergence as principally associated with increases in activity within frontal motor regions, whereas modulation of the amplitude of established tremor relates to changes in cerebellar activity. These findings progress a mechanistic understanding of ET and implicate network-level vulnerabilities in the rhythmic nature of communication throughout the brain.

The experiment investigated the influence of physiological tremor (8–12 Hz band) on the variability of isometric force control as a function of force level and hand dominance. Subjects were instructed to match a constant force level target line on a computer screen and minimize error in a uni-manual isometric finger abduction task at 5%, 25%, 45%, 65%, and 85% of their maximal voluntary contraction (MVC). The experimental protocol was performed independently with the left and right hands in separate blocks of performance. Tremor amplitude was enhanced at an increasing rate with increments of force level and was correlated with both performance outcome (Root mean square error – RMSE) and time-dependent regularity (Sample Entropy) of the force signal. No significant findings in force variability (dispersion or irregularity) were found between the dominant and non-dominant hands. Physiological tremor has a small but direct influence on the dispersion and time dependent structure of the variability of isometric force control but its relative influence on force amplitude decreases with increments of force level.

We investigate the differential diagnostic value of tremor analysis of EMG on Parkinson’s disease (PD), essential tremor (ET), and enhanced physiological tremor (EPT). Clinical data from 25 patients with PD, 20 patients with ET, and 20 patients with EPT were collected. The tremor frequency and muscle contraction pattern of the resting, posture, and 500 g and 1000 g overload were recorded. The frequency of PD tremor was 4–6 Hz, and the frequency of ET was also in this range; the frequency of EPT is 6–12 hz having some overlap with PD. The muscle contraction patterns of the ET and EPT group were mainly synchronous contraction, and the muscle contraction mode of the PD group was mainly alternating contraction. Having tremor latency from rest to postural position and having changes in tremor amplitude after mental concentration in PD might distinguish ET. Tremor analysis of EMG was able to distinguish PD from ET and EPT by varying the tremor frequency and muscle contraction pattern. It can also differentiate between PD and ET by the latency and concentration effect and ET and EPT by weight load effect.

Objectives 1) to evaluate the efficacy of medical cannabinoids (MC) by appraising the quality of evidence from clinical studies 2) to explore the factors hampering the MC use in clinical practice of Parkinson's disease (PD). Methods We performed a systematic review through various databases. The quality of 14 studies was assessed by Cochrane risk bias (5 randomized controlled trials- RCT) and Newcastle-Ottawa scale (9 uncontrolled studies). Results The positive effects on motor (5 studies) and non-motor symptoms (4 studies) described in uncontrolled studies have not been confirmed by the few and small RCTs. Only one RCT found a reduction of levodopa-induced dyskinesias, another a reduction in anxiety and tremor amplitude in an anxiogenic situation, while the remaining three without effect on motor/non-motor symptoms. Physical and psychological symptoms are among the most common side effects. Conclusions There is insufficient evidence to reform international legislation regarding cannabis use in PD practice.

BACKGROUND: We have observed in the clinic that a number of patients with Parkinson's disease (PD) can suppress their tremor at will for brief periods, by conscious mental processes. To our knowledge, the ability to consciously diminish one's resting tremor has not yet been reported nor assessed quantitatively. OBJECTIVE: To provide the first detailed systematic investigation of the phenomenon of voluntary tremor suppression in PD. METHODS: We examined changes in tremor characteristics during voluntary tremor suppression in 37 PD patients (on medication) presenting with rest tremor in their upper limb. We measured tremor oscillations with a triaxis accelerometer on the index finger of the most‐affected hand (n = 27). With surface electromyography (EMG), we measured changes in neuromuscular activity of the forearm flexor digitorum superficialis and extensor digitorum muscles (n = 15). Participants completed four 1‐minute trials, consisting of alternating consecutive 30‐second periods of resting tremor and 30‐second periods of attempted tremor suppression. RESULTS: Bayesian multilevel modeling revealed that attempted voluntary tremor suppression did indeed reduce tremor amplitude (peak power) of the acceleration signal and increased tremor frequency of the acceleration and EMG signals. Relative EMG power in the 3‐ to 8‐Hz tremor band was also smaller. Tremor suppression was not by enhanced voluntary contraction of the relevant muscle pairs. CONCLUSIONS: We present novel empirical evidence that PD resting tremor can be suppressed by an act of will, as evidenced by significant modulation of key neurophysiological tremor characteristics. These data highlight that it is possible to exert significant conscious control over parkinsonian resting tremor.

Introduction: Distinguishing between different tremor disorders can be challenging. Some tremor disorders are thought to have typical tremor characteristics: the current study aims to provide sensitivity and specificity for five 'typical' tremor phenomena.Methods: Retrospectively, we examined 210 tremor patients referred for electrophysiological recordings between January 2008 and January 2014. The final clinical diagnosis was used as the gold standard. The first step was to determine whether patients met neurophysiological criteria for their type of tremor. Once established, we focused on 'typical' characteristics: tremor frequency decrease upon loading (enhanced physiological tremor (EPT)), amplitude increase upon loading, distractibility and entrainment (functional tremor (Fr)), and intention tremor (essential tremor (ET)). The prevalence of these phenomena in the 'typical' group was compared to the whole group.Results: Most patients (87%) concurred with all core clinical neurophysiological criteria for their tremor type. We found a frequency decrease upon loading to be a specific (95%), but not a sensitive (42%) test for EPT. Distractibility and entrainment both scored high on sensitivity (92%, 91%) and specificity (94%, 91%) in FL whereas a tremor amplitude increase was specific (92%), but not sensitive (22%). Intention tremor was a specific finding in ET (85%), but not a sensitive test (45%). Combination of characteristics improved sensitivity.Conclusion: In this study, we retrospectively determined sensitivity and specificity for five 'typical' tremor characteristics. Characteristics proved specific, but few were sensitive. These data on tremor phenomenology will help practicing neurologists to improve distinction between different tremor disorders. (C) 2016 Elsevier Ltd. All rights reserved.

The International Parkinson and Movement Disorder Society established a task force on tremor that reviewed the use of transducer-based measures in the quantification and characterization of tremor. Studies of accelerometry, electromyography, activity monitoring, gyroscopy, digitizing tablet-based measures, vocal acoustic analysis, and several other transducer-based methods were identified by searching PubMed.gov. The availability, use, acceptability, reliability, validity, and responsiveness were reviewed for each measure using the following criteria: (1) used in the assessment of tremor; (2) used in published studies by people other than the developers; and (3) adequate clinimetric testing. Accelerometry, gyroscopy, electromyography, and digitizing tablet-based measures fulfilled all three criteria. Compared to rating scales, transducers are far more sensitive to changes in tremor amplitude and frequency, but they do not appear to be more capable of detecting a change that exceeds random variability in tremor amplitude (minimum detectable change). The use of transducer-based measures requires careful attention to their limitations and validity in a particular clinical or research setting. © 2016 International Parkinson and Movement Disorder Society.

Background An objective evaluation of tremor severity is necessary to document the course of disease, the efficacy of treatment, or interventions in clinical trials. Most available objective quantification devices are complex, immobile, or not validated. New method We used the TREMITAS-System that comprises a pen-shaped sensor for tremor quantification. The Power of Main Peak and the Total Power were used as surrogate markers for tremor amplitude. Tremor severity was assessed by the TREMITAS-System and relevant subscores of the MDS-UPDRS and TETRAS rating scales in 14 patients with Parkinson's disease (PD) and 16 patients with Essential tremor (ET) off and on therapy. We compared tremor amplitudes assessed during wearable and hand-held constellations. Results We found significant correlations between tremor amplitudes captured by TREM and tremor severity assessed by the MDS-UPDRS in PD (r = 0.638–0.779) and the TETRAS in ET (r = 0.597–0. 704) off and on therapy. The TREMITAS-System captured the L-Dopa-induced improvement of tremor in PD patients (p = 0.027). Tremor amplitudes did not differ between the handheld and wearable constellation (p > 0.05). Comparison with existing methods We confirm the results of previous studies using inertial based sensors that tremor severity and drug-induced changes of tremor severity can be quantified using inertial based sensors. The assessment of tremor amplitudes was not influenced by using a handheld or wearable constellation. Conclusions The TREMITAS-System can be used to quantify rest tremor in PD and postural tremor in ET and is capable of detecting clinically relevant changes in tremor in clinical and research settings., Accelerometer; Essential tremor; Mobile Monitoring; Parkinson's disease; Pen-Shaped Sensor; Tremor; Biomedical engineering; Biomedical Devices; Neurology; Clinical Research; Diagnostics; Biomarkers

Current treatments for parkinsonian tremor, such as medication and brain surgery, have shown varying levels of effectiveness and carry the risk of significant side effects and complications. Studies on wearable tremor suppression devices have shown positive results in the use of mechanical and electrical suppression on tremor management of the upper limbs. Wearable technology for tremor suppression is a promising solution for patients who do not respond to medication and do not present severe enough symptoms to undergo surgery. Available tremor suppression devices are mainly for elbow and wrist tremor. Devices for finger tremor suppression have not been developed despite the fact that finger tremor is also present. In this study, a wearable tremor suppression glove prototype was designed and validated with recorded tremor data from patients with Parkinson's disease. Two validation experiments were conducted to assess the performance of the proposed device when suppressing tremor motion and following voluntary motion. The tremor suppression assessment showed an overall tremor amplitude reduction of $\pmb{85.0\% \pm 8.1\%}$ , and the power reductions for the Ist, 2nd, and 3rd harmonics are $\pmb{87.9\%\pm .6\%, 92.0\%\pm .4\%}$ , and $\pmb{81.7\% \pm 13.0\%}$ , respectively. Following voluntary motion was possible with a RMSE of $\pmb{14.2\%\pm .5\%}$ and a correlation coefficient of $\pmb{0.97\pm 0.01}$ . Both assessments have shown positive results for the validation of the proposed device; however, further work is needed to improve the performance of the proposed device prior to human trials.

Transcranial alternating current stimulation (tACS) is a noninvasive neuromodulation method that can entrain physiological tremor in healthy volunteers. We conducted two experiments to investigate the effectiveness of high-amplitude and focused tACS montages at entraining physiological tremor. Experiment 1 used saline-soaked sponge electrodes with an extra-cephalic return electrode and compared the effects of a motor (MC) and prefrontal cortex (PFC) electrode location. Average peak-amplitude was 1.925 mA. Experiment 2 used gel-filled cup-electrodes in a 4 × 1 focused montage and compared the effects of MC and occipital cortex (OC) tACS. Average peak-amplitude was 4.45 mA. Experiment 1 showed that unfocused MC and PFC tACS both produced phosphenes and significant phase entrainment. Experiment 2 showed that focused MC and OC tACS produced no phosphenes but only focused MC tACS caused significant phase entrainment. At the group level, tACS did not have a significant effect on tremor amplitude. However, with focused tACS there was a significant correlation between phase entrainment and tremor amplitude modulation: subjects with higher phase entrainment showed more tremor amplitude modulation. We conclude that: (1) focused montages allow for high-amplitude tACS without phosphenes and (2) high amplitude focused tACS can entrain physiological tremor. ispartof: Scientific Reports vol:8 issue:1 ispartof: location:England status: published

In the present study, we analyze the seismic signals from a continuous volcanic tremor that occurred during a small phreatic eruption of the Hakone volcano, in the Owakudani geothermal region of central Japan, on June 29, 2015. The signals were detected for 2 days, from June 29 to July 1, at stations near the vents. The frequency component of the volcanic tremors showed a broad peak within 1–6 Hz. The characteristics of the frequency component did not vary with time and were independent of the amplitude of the tremor. The largest amplitude was observed at the end of the tremor activity, 2 days after the onset of the eruption. We estimated the location of the source using a cross-correlation analysis of waveform envelopes. The locations of volcanic tremors are determined near the vents of eruption and the surface, with the area of the upper extent of an open crack estimated using changes in the tilt. The duration-amplitude distribution of the volcanic tremor was consistent with the exponential scaling law rather than the power law, suggesting a scale-bound source process. This result suggests that the volcanic tremor originated from a similar physical process occurring practically in the same place. The increment of the tremor amplitude was coincident with the occurrence of impulsive infrasonic waves and vent formations. High-amplitude seismic phases were observed prior to the infrasonic onsets. The time difference between the seismic and infrasonic onsets can be explained assuming a common source located at the vent. This result suggests that both seismic and infrasonic waves are generated when a gas slug bursts at that location. The frequency components of the seismic phases observed just before the infrasonic onset were generally consistent with those of the tremor signals without infrasonic waves. The burst of a gas slug at the surface vent may be a reasonable model for the generation mechanism of the volcanic tremor and the occurrence of impulsive infrasonic signals.

We aimed to determine the effect of task-specific kinetic finger tremor, as indexed by surface electromyography (EMG), on the accuracy of a carrom stroke. Surface EMG of extensor digitorum communis muscle of the playing arm was recorded during rest, isometric contraction and stroke execution in 17 male carrom players with clinically observed finger tremor and 18 skill- and age-matched controls. Log-transformed power spectral densities (LogPSDs) of surface EMG activity (signifying tremor severity) at a 1-s pre-execution period correlated with angular error of the stroke. LogPSDs in 4-10 Hz range were higher in players with tremor than controls during pre-execution (P 0.001), but not during the resting state (P = 0.067). Pre-execution tremor amplitude correlated with angular deviation (r = 0.45, P = 0.007). For the first time, we document a task-specific kinetic finger tremor in carrom players. This finger tremor during the immediate pre-execution phase appears to be a significant determinant of stroke accuracy.

Tremor is a rhythmical and involuntary oscillatory movement of a body part. In addition to social embarrassment, tremor can be debilitating for daily activities. Recently, wearable active exoskeletons emerged as a noninvasive tremor suppression alternative to medication or surgery. The challenge in muscu- loskeletal tremor suppression is identifying and attenuating the tremor motion without adding resistance to the patient's inten- tional motion. In this research, an adaptive tremor suppression algorithm was designed to estimate the tremor fundamental fre- quency and calculate the proper suppressive force to be applied by the orthosis to the patient's arm. Stability of the closed-loop system and robustness against the parametric uncertainties were analyzed. An experimental setup was designed and developed to emulate the dynamics of a human wrist with intentional and tremor motion. A pneumatic cylinder and a sliding mode integral controller was used to apply orthotic suppressive force. The algorithm was im- plemented with an NI cRIO real-time controller and tested using clinical data from ten patients with severe pathological tremor. Ex- perimental results showed tracking of the tremor frequency with less than 3-s response time, and an average 34.5 dB (98.1%) and 11.8 dB (74.3%) reduction of tremor amplitude at the fundamental and second-harmonic frequencies, respectively. The average resis- tance force to the intentional motion was 0.7 N and the average position error was 2.08% (0.18 dB). The results were compared with passive tremor suppression using a tunable magnetorheolog- ical damper.

Background Deep brain stimulation (DBS) treats the symptoms of several movement disorders, but optimal selection of stimulation parameters remains a challenge. The evoked compound action potential (ECAP) reflects synchronized neural activation near the DBS lead, and may be useful for feedback control and automatic adjustment of stimulation parameters in closed-loop DBS systems. Objectives Determine the feasibility of recording ECAPs in the clinical setting, understand the neural origin of the ECAP and sources of any stimulus artifact, and correlate ECAP characteristics with motor symptoms. Methods The ECAP and tremor response were measured simultaneously during intraoperative studies of thalamic DBS, conducted in patients who were either undergoing surgery for initial lead implantation or replacement of their internal pulse generator. Results There was large subject-to-subject variation in stimulus artifact amplitude, which model-based analysis suggested may have been caused by glial encapsulation of the lead, resulting in imbalances in the tissue impedance between the contacts. ECAP recordings obtained from both acute and chronically implanted electrodes revealed that specific phase characteristics of the signal varied systematically with stimulation parameters. Further, a trend was observed in some patients between the energy of the initial negative and positive ECAP phases, as well as secondary phases, and changes in tremor from baseline. A computational model of thalamic DBS indicated that direct cerebellothalamic fiber activation dominated the clinically measured ECAP, suggesting that excitation of these fibers is critical in DBS therapy. Conclusions This work demonstrated that ECAPs can be recorded in the clinical setting and may provide a surrogate feedback control signal for automatic adjustment of stimulation parameters to reduce tremor amplitude.

Objective Test the hypotheses that tremor amplitude in musicians with task-specific dystonia is higher at the affected finger (dystonic tremor, DT) or the adjacent finger (tremor associated with dystonia, TAD) than (1) in matched fingers of healthy musicians and non-musicians and (2) within patients in the unaffected and non-adjacent fingers of the affected side within patients. Methods We measured 21 patients, 21 healthy musicians and 24 non-musicians. Participants exerted a flexion–extension movement. Instantaneous frequency and amplitude values were obtained with empirical mode decomposition and a Hilbert-transform, allowing to compare tremor amplitudes throughout the movement at various frequency ranges. Results We did not find a significant difference in tremor amplitude between patients and controls for either DT or TAD. Neither differed tremor amplitude in the within-patient comparisons. Conclusion Both hypotheses were rejected and apparently neither DT nor TAD occur in musician’s dystonia of the fingers. Significance This is the first study assessing DT and TAD in musician’s dystonia. Our finding suggests that even though MD is an excellent model for malplasticity due to excessive practice, it does not seem to provide a good model for DT. Rather it seems that musician’s dystonia may manifest itself either as dystonic cramping without tremor or as task-specific tremor without overt dystonic cramping.

The purpose of this study was to investigate hand–finger tremor dynamics when a load was applied to the finger in a group of healthy older adults. Moreover, we sought to determine if projecting a representation of the subject's finger tremor on a target was capable of overcoming the effects of loading so that hand–finger interactions returned to a state that was similar to normal tremor. Eight healthy older males (67 ± 1 year) performed a postural pointing task, where tremor was assessed using lightweight accelerometers attached to the hand and finger. Tremor was then assessed when a laser pointer was attached to the finger and switched off (the load), and then with the laser pointer attached and switched on pointing at targets of 40 mm and 20 mm in diameter. The main findings of this study were that 1) loading the finger resulted in a reduction in finger tremor amplitude and increased finger tremor regularity, but no change in hand tremor, 2) loading caused increased hand–finger 8–12 Hz cross wavelet coherence and phase synchrony, and 3) pointing at different targets while the finger was loaded resulted in an increase in finger tremor amplitude, and changes in inter-segmental coupling to the extent that hand–finger dynamics reflected normal unloaded conditions. Overall, these results illustrate that the damping effects of limb loading can be offset, in part, by altering the accuracy demands of the task to make the pointing action more challenging.

A great proportion of essential tremor (ET) patients have not so far been able to receive functional benefits from traditional therapies. In this regard, the use of functional electrical stimulation (FES) has been proposed for reducing tremor amplitude by stimulating muscles in antiphase with respect to the trembling motion. Although some studies have reported success in terms of tremor attenuation, drawbacks still exist that prevent the method from being used in real-life applications. In this article, we explore an alternative approach: a strategy based on the hypothesis that FES-induced constant muscle contraction may provide functional benefit for tremor patients. To evaluate the proposed strategy, experiments were conducted in which stimulation was intermittently turned on and off while the subjects performed a static motor task. The results of the proposed experimental protocol indicate that tremor attenuation using this strategy is feasible, as consistent tremor attenuation levels were obtained in eight out of 10 ET patients. Nonetheless, tremor reduction was not instantaneous for all successful trials, indicating that prior training with FES may improve the overall response. Furthermore, although simpler assistive devices may potentially be designed based on this technique, some experimental difficulties still exist, which suggests that further studies are necessary.

Tremor is a manifestation of a variety of human neurodegenerative diseases, notably Parkinson’s disease (PD) and Essential Tremor (ET), both affecting millions worldwide. PD is primarily caused by a progressive loss of dopamine neurons in the nigrostriatal system that leads to widespread motor symptoms such as bradykinesia, rigidity, tremor and postural instability. ET typically involves a tremor of the arms, hands or fingers. No definitive test or biomarker is yet available for PD or ET, so the rate of misdiagnosis is relatively high. As tremor is a very common feature at the onset of both diseases, it is crucial to be able to characterize it. This is made possible using acce?lerometers to quantify the tremor amplitude and frequency. In this work we aim to find tasks involving upper limb movements that are suitable to modulate both types of tremor. Four tasks were tested, differing on whether the arms moved together or alternatingly and whether loads were added. Significant differences in tremor measures were found when patients were asked to perform simultaneous rapid arms movements with loads placed on their wrists. These results may allow the design of an efficient fMRI protocol for identifying the cortical circuits responsible for the modulation of tremor.

Background We explored whether a noninvasive handheld device using Active Cancellation of Tremor (ACT) technology could stabilize tremor-induced motion of a spoon in individuals with essential tremor (ET). Methods Fifteen ET subjects (9 men, 6 women) performed 3 tasks with the ACT device turned on and off. Tremor severity was rated with the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). Subjective improvement was rated by subjects with the Clinical Global Impression Scale (CGI-S). Tremor amplitude was measured using device-embedded accelerometers in 11 subjects. Results TRS scores improved with ACT on (versus off) in all 3 tasks: holding (1.00 ± 0.76 vs. 0.27 ± 0.70; P = 0.016), eating (1.47 ± 1.06 vs. 0.13 ± 0.64; P = 0.001), and transferring (1.33 ± 0.82 vs. 0.27 ± 0.59; P = 0.001). CGI-S improved with eating and transferring, but not the holding task. Accelerometer measurements demonstrated 71% to 76% reduction in tremor with the ACT device on. Conclusions This noninvasive handheld ACT device can reduce tremor amplitude and severity for eating and transferring tasks in individuals with ET. © 2013 International Parkinson and Movement Disorder Society

[1] We provide a new link between tectonic tremor propagation, tremor amplitude, and tidal stresses by analyzing high-resolution tremor locations and amplitudes determined by multibeam backprojection of data from an array of subarrays. For two Cascadia episodic tremor and slip events, we observe repeating, high-amplitude rapid tremor reversals (RTRs) and tremor streaks. They tend to occur when tremor amplitudes are highest and occur almost exclusively during periods of thrust-encouraging, tidally induced shear stress on the fault. We speculate that thrust-encouraging shear stress from tidal loading forces trigger RTRs and streaks that energetically rerupture the weakened fault behind the slow slip front. The high rate and amplitude of tremor during RTRs and streaks stands in contrast to the hypothesis that activity at the leading edge of the slow slip zone is the most energetic and loudest. This implies that the spatiotemportal pattern of slow earthquake slip migration is even more intricate than previously reported.

Objectives/Hypothesis 1) To clarify essential voice tremor (EVT) phenomenology; 2) To report a management paradigm for essential voice tremor using botulinum toxin. Study Design Retrospective analysis of prospectively collected data. Methods Phenomenology from patients diagnosed with EVT between April 1996 and March 2012 was recorded, charted, and analyzed. A paradigm for treatment of EVT using botulinum toxin based on individualized clinical findings is discussed. Results Sixteen patients were included. Fewer than 50% patients were responsive to centrally acting oral medications. Fifteen patients analyzed had horizontal laryngeal tremor and received botulinum toxin injections to bilateral thyroarytenoid muscles. Thirteen patients had a vertical laryngeal tremor, and these patients underwent additional strap muscle injections. All patients had symptomatic improvement with reduced tremor amplitude. Dose adjustments over time depended on degree of symptomatic improvement. Conclusions Management of essential voice tremor with botulinum toxin is optimized by individualizing treatment based on the tremor phenomenology observed during clinical examination. Level of Evidence 4. Laryngoscope, 123:2497–2501, 2013

[1] We use borehole strain and seismic data to show that slow slip and tremor in central Cascadia are correlated on a range of time scales shorter than 1 day. The recorded strain rate is our proxy for the slow slip moment rate, and the seismic amplitude is our proxy for the tremor amplitude. We find that, on average, the strain rate is higher when the seismic amplitude is larger. This correlation persists on time scales between 15 min and 16 h, and it can be seen in each of the five slow slip events between 2007 and 2011. Our results imply that the slow slip moment rate varies by a large amount even at these short time scales. For instance, we observe a factor of 2 variation on time scales shorter than 4 h. This apparently aperiodic variation is larger than the previously observed variation in moment rate resulting from tidal forcing. It is a lower bound on the actual moment rate variation, as we detect only changes in slow slip that are correlated with tremor amplitude.