Mechanism Of Tremor Research Articles

Decreased EAAT2 protein expression in the essential tremor cerebellar cortex.

Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons. Therefore, the expression level of glutamate transporters could be important in essential tremor pathogenesis. Using Western blotting, we compared the expression levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched controls. We also studied the localization of EAAT1 and EAAT2 using immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein levels were similar in cases and controls (1.12 ± 0.83 vs. 1.01 ± 0.69, p =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of that in controls (0.35 ± 0.23 vs. 1.00 ± 0.62, p < 0.01). Interestingly, EAAT2, but not EAAT1, was expressed in astrocytic processes surrounding the Purkinje cell axon initial segment, a region of previously observed pathological changes in essential tremor. Our main finding, a significant reduction in cerebellar cortical EAAT2 protein levels in essential tremor, suggests that Purkinje cells in essential tremor might be more vulnerable to excitotoxic damage than those of controls.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-014-0157-z) contains supplementary material, which is available to authorized users.

Rest tremor suppression may separate essential from parkinsonian rest tremor

Rest tremor at 4–6 Hz is typical for classical rest tremor (PT) of Parkinson's disease (PD). But rest tremor also appears in other tremor syndromes and may therefore cause a misdiagnosis. In this study we evaluated if suppression of tremor during movement onset is a characteristic feature of Parkinsonian Tremor distinguishing PT from Essential tremor (ET) and if this sign can be reliably diagnosed.Clinically diagnosed patients with PT (n = 44) and ET (n = 22) with rest tremor were included. Video sequences were recorded according to a standardized protocol focusing on the change of tremor amplitude during transition from rest to posture (test 1) or to a target-directed movement (test 2). These videos were assessed for rest tremor suppression by 4 reviewers (2 specialists and 2 residents) blinded to the clinical diagnosis and were compared to the personal assessment of an unblinded movement disorder specialist.Rest tremor suppression was found in 39/44 PD patients and in 2/22 patients with ET during the personal assessment. Rest tremor suppression showed a high sensitivity (0.92–1.00) and an acceptable specificity (0.69–0.95) for PD tremor in both tests. The interrater-reliability of the video-sequences was good to very good (κ 0.73–0.91). Less than 3% of the video sequences were misclassified.We conclude that the assessment of the suppression of rest tremor during movement initiation is a simple and reliable tool to separate PT from rest tremor in ET also suggesting that the mechanisms of rest tremor in these two diseases are different.

Focal Mechanisms of Mine-Induced Seismic Events an Explanation of Geomechanical Processes in the Area of Longwall 6, Seam 510 In Hard Coal Mine “Bobrek-Centrum” / Mechanizm Ognisk Indukowanych Wstrząsów Górniczych Wyjaśnieniem Procesów Geomechanicznych W Rejonie Ściany 6, Pokład 510 W Kopalni „Bobrek-Centrum”

Abstract Exploitation in a coal mine “Bobrek-Centrum” of the longwall 6 in seam 510 has led to the occurrence of very high seismic activity. From January 2011 to June 2012 took place almost 3500 tremors with the energy of 102-104 J and 95 tremors of energy more than to 105 J. In an attempt to identify the character of that seismicity, calculations of focal mechanism parameters were carried out, and according to them local stress field was determined. Three periods of exploitation of longwall 6 were distinguished which vary in type of focal mechanism. Tremors, which occurred in exploitation periods I and III were characterized by normal slip mechanism, occurred due to domination of vertical principal stresses σ1, horizontal intermediate stresses σ2 and minimal ones σ3. Such stress arrangement characterizes local state of rock mass behaviour as a result of cracking and collapse of sandstone, tremor-generating strata during advancing exploitation. In exploitation period II, of non-shearing mechanism of foci occurred. That was the period of change of longwall run from the NE-SW direction to E-W direction, that is the period of so called “slanting” of exploitation front. It can be presumed that this type of tremor mechanism could have occurred due to a sudden coal bed load by superimposed roof strata, which may have led to extreme load conditions and to a dynamic disintegration of seam part. It was confirmed by geomechanical calculations, which indicated that in the region of rockburst existence on 19.07.2011, layers which were located above and under seam 510 in area of longwall no. 6 were strongly deformed locally causing compression of certain parts of seam.

Harmaline Tremor: Underlying Mechanisms in a Potential Animal Model of Essential Tremor

<strong>Background:</strong> Harmaline and harmine are tremorigenic b-carbolines that, on administration to experimental animals, induce an acute postural and kinetic tremor of axial and truncal musculature. This drug-induced action tremor has been proposed as a model of essential tremor. Here we review what is known about harmaline tremor. <strong>Methods:</strong> Using the terms harmaline and harmine on PubMed, we searched for papers describing the effects of these <em>β</em>-carbolines on mammalian tissue, animals, or humans. <strong>Results:</strong> Investigations over four decades have shown that harmaline induces rhythmic burst-firing activity in the medial and dorsal accessory inferior olivary nuclei that is transmitted via climbing fibers to Purkinje cells and to the deep cerebellar nuclei, then to brainstem and spinal cord motoneurons. The critical structures required for tremor expression are the inferior olive, climbing fibers, and the deep cerebellar nuclei; Purkinje cells are not required. Enhanced synaptic norepinephrine or blockade of ionic glutamate receptors suppresses tremor, whereas enhanced synaptic serotonin exacerbates tremor. Benzodiazepines and muscimol suppress tremor. Alcohol suppresses harmaline tremor but exacerbates harmaline-associated neural damage. Recent investigations on the mechanism of harmaline tremor have focused on the T-type calcium channel. <strong>Discussion:</strong> Like essential tremor, harmaline tremor involves the cerebellum, and classic medications for essential tremor have been found to suppress harmaline tremor, leading to utilization of the harmaline model for preclinical testing of antitremor drugs. Limitations are that the model is acute, unlike essential tremor, and only approximately half of the drugs reported to suppress harmaline tremor are subsequently found to suppress tremor in clinical trials.

Harmaline tremor: underlying mechanisms in a potential animal model of essential tremor.

Harmaline and harmine are tremorigenic β-carbolines that, on administration to experimental animals, induce an acute postural and kinetic tremor of axial and truncal musculature. This drug-induced action tremor has been proposed as a model of essential tremor. Here we review what is known about harmaline tremor. Using the terms harmaline and harmine on PubMed, we searched for papers describing the effects of these β-carbolines on mammalian tissue, animals, or humans. Investigations over four decades have shown that harmaline induces rhythmic burst-firing activity in the medial and dorsal accessory inferior olivary nuclei that is transmitted via climbing fibers to Purkinje cells and to the deep cerebellar nuclei, then to brainstem and spinal cord motoneurons. The critical structures required for tremor expression are the inferior olive, climbing fibers, and the deep cerebellar nuclei; Purkinje cells are not required. Enhanced synaptic norepinephrine or blockade of ionic glutamate receptors suppresses tremor, whereas enhanced synaptic serotonin exacerbates tremor. Benzodiazepines and muscimol suppress tremor. Alcohol suppresses harmaline tremor but exacerbates harmaline-associated neural damage. Recent investigations on the mechanism of harmaline tremor have focused on the T-type calcium channel. Like essential tremor, harmaline tremor involves the cerebellum, and classic medications for essential tremor have been found to suppress harmaline tremor, leading to utilization of the harmaline model for preclinical testing of antitremor drugs. Limitations are that the model is acute, unlike essential tremor, and only approximately half of the drugs reported to suppress harmaline tremor are subsequently found to suppress tremor in clinical trials.

Shaking when stirred: mechanisms of physiological tremor

Shaking when stirred: mechanisms of physiological tremor

Believing is perceiving: mismatch between self-report and actigraphy in psychogenic tremor

We assessed the duration and severity of tremor in a real-life ambulatory setting in patients with psychogenic and organic tremor by actigraphy, and compared this with self-reports of tremor over the same period. Ten participants with psychogenic tremor and eight with organic tremor, diagnosed using standardized clinical criteria, were studied. In an explicit design, participants were asked to wear a small actigraph capable of continuously monitoring tremor duration and intensity for 5 days while keeping a diary of their estimates of tremor duration during the same period. Eight patients with psychogenic tremor and all patients with organic tremor completed the study. Psychogenic patients reported significantly more of the waking day with tremor compared with patients with organic tremor (83.5 ± 14.0% of the waking day versus 58.0 ± 19.0% of the waking day; P < 0.01), despite having almost no tremor recorded by actigraphy (3.9 ± 3.7% of the waking day versus 24.8 ± 7.7% of the waking day; P = 0.001). Patients with organic tremor reported 28% more tremor than actigraphy recordings, whereas patients with psychogenic tremor reported 65% more tremor than actigraphy. These data demonstrate that patients with psychogenic tremor fail to accurately perceive that they do not have tremor most of the day. The explicit study design we employed does not support the hypothesis that these patients are malingering. We discuss how these data can be understood within models of active inference in the brain to provide a neurobiological framework for understanding the mechanism of psychogenic tremor.

Seismic source mechanisms of tremor recorded on Arenal volcano, Costa Rica, retrieved by waveform inversion

Moment tensor inversions of volcanic tremor are synthetically tested and subsequently applied to a dataset recorded on Arenal volcano in 2005. We selected 15 harmonic tremor events showing an emergent but very clear onset with a fundamental frequency range of 0.8–1.5Hz. These events constitute an excellent opportunity to broaden our knowledge of tremor generation models. The inversions were performed for a common source location, the position of which was retrieved through the evaluation of the joint probability density function of the misfit values obtained by the moment tensor inversion of all the events and all predefined source locations (grid search). Events are located beneath the summit crater, in a shallow position. The inversion procedure was tested through the use of synthetic tremor, generated using full wavefield numerical simulations. The maximum amplitude decomposition method is used to analyse the solutions of the synthetic tests. The results highlight the stability of the moment tensor solution when the whole length of the signal is used in the inversion procedure. Hence the whole length of the tremor is utilised to retrieve the source mechanism generating the 15 tremor events. A sliding window is utilised to investigate the time variability of our solution. A crack dipping 20° to the North–Northeast is reconcilable with all 15 tremor events. This mechanism is found to be constant for the entire length of each tremor and for different events.

Mine tremor focal mechanism: An essential element for recognising the process of mine working destruction

This article presents an analysis of causes of rockburst which occurred in the Rydultowy-Anna Mine on 24 March 2010. The seismic phenomena and the rockburst hazard connected with them have been determined by a number of natural and technical factors. The dominant factors were the mechanical strength characteristics of coal and surrounding rocks, as well as the values of stress in the surroundings of mine workings. An analysis must take into account the structure of the strata, its susceptibility to rockbursts, development and displacement of areas with high values of stress, as well as critical levels of elastic deformation of the strata. Such an approach must be supported by the results of an analysis of focal mechanisms of tremors to make it possible to recognize mining and geological factors which had the prevailing influence on tremors’ location and energy. By presenting a selected example of a real event, the authors would like to point out the importance of the proper description of focal mechanisms of seismic tremors. The analysis of a chain of interacting destruction processes in the developed model of strata would give the explanation why the tremor occurred in the gallery located at a considerable distance from the tremor focus.

Coherence analysis of local field potentials in the subthalamic nucleus: differences in parkinsonian rest and postural tremor

Implantation of electrodes in the subthalamic nucleus (STN) for deep brain stimulation is a well-established method to ameliorate motor symptoms in patients suffering from Parkinson's disease (PD). This study investigated the pathophysiology of rest and postural tremor in PD. In 14 patients with PD, we recorded intraoperatively local field potentials (LFPs) in the STN (at different recording depths) and electromyographic signals (EMGs) of the contralateral forearm. Using coherence analysis we analysed tremor epochs both at rest and hold conditions in patients of the akinetic-rigid or of the tremor-dominant PD subtype. Data analysis revealed significant LFP-EMG coherence during periods of rest and postural tremor. However, strong differences between both tremor types were observed: local maxima (cluster) of rest and postural tremor did not match. Additionally, during rest tremor coherence occurred significantly more frequently at single tremor frequency than at double tremor frequency in tremor-dominant as well as in akinetic-rigid patients. In contrast, during postural tremor in patients with akinetic-rigid PD coherence was predominantly at double tremor frequency. The data suggest a specific topography of 'tremor clusters' for rest and postural tremor. Furthermore, we presume that the same tremor mechanisms exist in patients with tremor-dominant and akinetic-rigid PD, but to different degrees.

Interactive Tremor Monitoring

The purpose of this article is to explore new Web-based resources for disseminating data in an interactive and intuitive way that is accessible and engaging to the public without sacrificing scientific utility. This article highlights these new opportunities and describes their synthesis with recently developed automated tremor monitoring methodologies. The resulting product is a website that the reader may find useful to explore in tandem with this article, http://www.pnsn.org/tremor. In this article, the data dissemination example is specifically applied to Cascadia tremor, but the utilization of freely accessible Web applications to provide an interactive Web experience for the public and scientific community alike could easily be applied to many different aspects of seismology. Since their discovery nearly a decade ago, advances in both instrumentation and methodology in subduction zones around the world have brought the causal connection between seismically observed tectonic tremor (Obara 2002) and geodetically observed slow slip (Dragert et al. 2001) into sharper focus. In addition to the strong spatio-temporal correlation between the separately observed phenomena (Wech et al. 2009), mounting evidence indicates that deep, non-volcanic tremor represents slow shear (Ide et al. 2007; Wech and Creager 2007) occurring at the interface (Shelly et al. 2006, 2007) between the subducting oceanic and overriding continental plates, suggesting the two phenomena are different manifestations of the same process. Of course, there is still ongoing debate over the depth and mechanism of tectonic tremor (Kao et al. 2005; McCausland et al. 2005), but what is clear is that tremor serves as a proxy for slow slip. Considering geodesy's lower limits in spatial resolution and slow slip detection together with the abundance of low-level, ageodetic tremor, this connection makes tremor a key component for monitoring when, where, and how much slip is occurring. Because slow slip transfers stress …

Analyses of motor unit firing patterns and synchrony contribute to our understanding of tremor mechanisms in Parkinson’s disease

Analyses of motor unit firing patterns and synchrony contribute to our understanding of tremor mechanisms in Parkinson’s disease

Complex nonvolcanic tremor near Parkfield, California, triggered by the great 2004 Sumatra earthquake

In several instances, the passing surface waves from large earthquakes have ignited nonvolcanic tremor (NVT) on major faults. Still, the mechanism of tremor and its reaction to the dynamic stressing from various body and surface waves is poorly understood. We examine tremor near Parkfield, California, beneath the San Andreas fault triggered by the Mw 9.2, 2004 Sumatra earthquake. The prolonged shaking produces the richest and the most varied observations of dynamically triggered tremor to date. The tremor appears in at least three distinct locations and shows activity pulsing with encouraging stress, as has been observed in other cases. The greatest amount of triggering and tremor modulation accompanies the long‐period Love waves. Rayleigh waves, on the other hand, appear to be less effective in exciting tremor sources. Also, at times, the tremor stops before the surface waves are complete, at other times it continues quivering after the waves have passed. While tremor is found to be sensitive to small stress changes, there are times when stresses of comparable magnitudes do not trigger noticeable tremor. Some tremors in this NVT sequence appear to be associated with the passage of P waves, which is unusual and surprising given the small stresses they impart.

Seismic evidence for overpressured subducted oceanic crust and megathrust fault sealing

Water and hydrous minerals play a key part in geodynamic processes at subduction zones by weakening the plate boundary, aiding slip and permitting subduction-and indeed plate tectonics-to occur. The seismological signature of water within the forearc mantle wedge is evident in anomalies with low seismic shear velocity marking serpentinization. However, seismological observations bearing on the presence of water within the subducting plate itself are less well documented. Here we use converted teleseismic waves to obtain observations of anomalously high Poisson's ratios within the subducted oceanic crust from the Cascadia continental margin to its intersection with forearc mantle. On the basis of pressure, temperature and compositional considerations, the elevated Poisson's ratios indicate that water is pervasively present in fluid form at pore pressures near lithostatic values. Combined with observations of a strong negative velocity contrast at the top of the oceanic crust, our results imply that the megathrust is a low-permeability boundary. The transition from a low- to high-permeability plate interface downdip into the mantle wedge is explained by hydrofracturing of the seal by volume changes across the interface caused by the onset of crustal eclogitization and mantle serpentinization. These results may have important implications for our understanding of seismogenesis, subduction zone structure and the mechanism of episodic tremor and slip.

Hypothetical membrane mechanisms in essential tremor

BackgroundEssential tremor (ET) is the most common movement disorder and its pathophysiology is unknown. We hypothesize that increased membrane excitability in motor circuits has a key role in the pathogenesis of ET. Specifically, we propose that neural circuits controlling ballistic movements are inherently unstable due to their underlying reciprocal innervation. Such instability is enhanced by increased neural membrane excitability and the circuit begins to oscillate. These oscillations manifest as tremor.MethodsPostural limb tremor was recorded in 22 ET patients and then the phenotype was simulated with a conductance-based neuromimetic model of ballistic movements. The model neuron was Hodgkin-Huxley type with added hyperpolarization activated cation current (Ih), low threshold calcium current (IT), and GABA and glycine mediated chloride currents. The neurons also featured the neurophysiological property of rebound excitation after release from sustained inhibition (post-inhibitory rebound). The model featured a reciprocally innervated circuit of neurons that project to agonist and antagonist muscle pairs.ResultsNeural excitability was modulated by changing Ih and/or IT. Increasing Ih and/or IT further depolarized the membrane and thus increased excitability. The characteristics of the tremor from all ET patients were simulated when Ih was increased to ~10× the range of physiological values. In contrast, increasing other membrane conductances, while keeping Ih at a physiological value, did not simulate the tremor. Increases in Ih and IT determined the frequency and amplitude of the simulated oscillations.ConclusionThese simulations support the hypothesis that increased membrane excitability in potentially unstable, reciprocally innervated circuits can produce oscillations that resemble ET. Neural excitability could be increased in a number of ways. In this study membrane excitability was increased by up-regulating Ih and IT. This approach suggests new experimental and clinical ways to understand and treat common tremor disorders.

The role of the thalamus and basal ganglia in parkinsonian tremor.

The mechanism of parkinsonian tremor may involve a central oscillator, peripheral feedback to the central nervous system (CNS), or both. The thalamus or the globus pallidus is the most likely site for a central oscillator and would be predicted to generate thalamic tremor-related activity characterized, respectively, by calcium spike-associated bursts and by maximal tremor-related activity in the pallidal relay nucleus of thalamus. Thalamic spike trains demonstrate neither of these characteristics. However, cross-correlation, latency, and transfer function analysis indicate that sensory feedback is a critical element in the relationship between thalamic activity and parkinsonian tremor. Therefore, thalamic spike train activity is most consistent with parkinsonian tremor being mediated by peripheral inputs involved in either an unstable reflex loop or sensory modulation of a central oscillator.

Nonlinear dynamic mechanism of vocal tremor from voice analysis and model simulations

Nonlinear dynamic analysis and model simulations are used to study the nonlinear dynamic characteristics of vocal folds with vocal tremor, which can typically be characterized by low-frequency modulation and aperiodicity. Tremor voices from patients with disorders such as paresis, Parkinson's disease, hyperfunction, and adductor spasmodic dysphonia show low-dimensional characteristics, differing from random noise. Correlation dimension analysis statistically distinguishes tremor voices from normal voices. Furthermore, a nonlinear tremor model is proposed to study the vibrations of the vocal folds with vocal tremor. Fractal dimensions and positive Lyapunov exponents demonstrate the evidence of chaos in the tremor model, where amplitude and frequency play important roles in governing vocal fold dynamics. Nonlinear dynamic voice analysis and vocal fold modeling may provide a useful set of tools for understanding the dynamic mechanism of vocal tremor in patients with laryngeal diseases.

Irregularity distinguishes limb tremor in cervical dystonia from essential tremor

Introduction:Patients with cervical dystonia (CD) often have limb tremor that is clinically indistinguishable from essential tremor (ET). Whether a common central mechanism underlies the tremor in these conditions is unknown....

Update on pathogenesis and treatment of essential tremor

This review focuses on recent findings on the aetiological, clinical, pathological and genetic heterogeneity of essential tremor and new therapeutic approaches. Although essential tremor is one of the most common movement disorders, understanding of the causes and mechanisms of the disease is still very limited. Studies on the clinical presentation of essential tremor have expanded the clinical dimension, now including nontremor manifestations such as cerebellar signs, neuropsychological characteristics, distinct personality traits and behavioural symptoms. Results of neuropathologic and imaging studies are conflicting, with hints of neurodegeneration or a nondegenerative disturbance of functional circuits or receptors. Genetic heterogeneity of essential tremor has been demonstrated by linkage to three different chromosomal loci so far, and several negative genetic studies. New animal models are reinforcing previous hypotheses about gamma-aminobutyrate (GABA)-ergic mechanisms in essential tremor. New therapeutic agents for essential tremor have been tested and demonstrated to be partly effective. The traditional view of essential tremor as a single disease entity has been replaced with the concept that this disorder is a complex and heterogeneous disease. Heterogeneity of the condition, and lack of diagnostic criteria and objective diagnostic tests add to this problem. Many conflicting results may be due to differences in patient selection.

Parallel Neuronal Mechanisms Underlying Physiological Force Tremor in Steady Muscle Contractions of Humans

We present results from a study of the 6-to 12-Hz force tremor in relation to motor unit (MU) firing synchrony. Our experimental observations from 32 subjects, 321 contractions, and 427 recorded MUs reveal that tremor is accompanied by corresponding, in-phase MU rhythms that are additional to the ones at the MU intrinsic firing rates. This rhythmical synchrony is widespread and has a uniform strength that ranges from near zero to very large (MU/MU coherence > 0.50) in different contractions. Both the synchrony and the tremor are suppressed during ischemia, and this strongly suggests an involvement of spindle feedback in their generation. Furthermore, in the presence of substantial synchrony, the tremor enhancement, relative to the minimal tremor of ischemia, reflects the strength of the synchrony. Theoretical considerations based on these observations indicate that the muscle force signal is expected to show 1) frequency components in the band of the firing rates of the last-recruited, large MUs, and 2) because of the synchronized MU rhythms, an additional, distinct component with a size reflecting the strength of synchrony. Furthermore, synchronized MU rhythms, with frequencies in the 6- to 12-Hz range, are expected to arise from self-oscillations in the monosynaptic stretch reflex loop, due primarily to the associated muscle delay (several tens of milliseconds). Our results therefore reveal the parallel action of two tremor mechanisms, one of which involves MU synchrony probably caused by loop action. Clearly, the results on the synchrony and its impact also apply to other possible generators of tremor synchrony, including supraspinal ones.