Tremor Period Research Articles

Antiparkinsonian activity of new N-methyl-D-aspartate receptor ligands in the arecoline hyperkinesis test

Introduction. Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the population of older patients. Even though long-term combination therapy helps to cope with the main manifestations of PD. It inevitably leads to the appearance of such side effects as drowsiness, hallucinations, dyskinesia, and many others. [12]. Therefore, the search for effective antiparkinsonian drugs devoid of the above-mentioned adverse reactions remains an urgent task of modern neuropharmacology.The explored substances are derivatives of imidazole-4,5-dicarboxylic acid. These compounds belong to a fundamentally new class of N-methyl-D-aspartate ligands (NMDA) that are not channel blockers. Their pharmacological effect is realized due to interaction with the NMDA receptor recognition site, which, along with high efficiency, allows us to assume their higher safety, compared to previously existing channel blockers from the NMDA ligand group.Objective. Studing of the antiparkinsonian activity of new ligands of the glutamate NMDA-receptor complex-1,2-substituted imidazole-4,5-dicarboxylic acids on an experimental model of arecoline hyperkinesis.Materials and methods. Imidazole-dicarboxylic acid derivatives (IEM2258, IEM2248, IEM2247, and IEM1574) were injected into the lateral ventricles of the mouse brain 10 minutes before arecoline in a volume of 5 µl at doses of 0.1-0.5 µmol, then the latent period, intensity, and duration of tremor were recorded. Amantadine was used as a comparison drug.Results. Preliminary administration of the studied examined substances led to a significant decrease in the intensity and duration of arecoline tremor. The highest inhibitory activity with respect to the intensity and duration of the experimental tremor was demonstrated with the introduction of the compound IEM-2247 (at a dose of 0.1-0.5 mmol, the duration of the latent period of the tremor was 1.7-2.3 times longer than the control one, respectively, the duration of the tremor decreased by 1.5 - 2.5 times).Conclusions. The dose-dependent antiparkinsonian activity of imidazole-dicarboxylic acid derivatives is shown, indicating the prospects for the development of these substances and the further search for effective and safe antiparkinsonian agents among the compounds of this class.

Risk Factors for Tremor in a Population of Patients with Severe Mental Illness: An 18-year Prospective Study in a Geographically Representative Sample (The Curacao Extrapyramidal Syndromes Study XI).

BackgroundThe aim was to assess incidence, prevalence and risk factors of medication-induced tremor in African-Caribbean patients with severe mental illness (SMI).MethodA prospective study of SMI patients receiving care from the only mental health service of the previous Dutch Antilles. Eight clinical assessments, over 18 years, focused on movement disorders, medication use, and resting tremor (RT) and (postural) action tremor (AT). Risk factors were modeled with logistic regression for both current (having) tremor and for tremor at the next time point (developing). The latter used a time-lagged design to assess medication changes prior to a change in tremor state.ResultsYearly tremor incidence rate was 2.9% and mean tremor point prevalence was 18.4%. Over a third of patients displayed tremor during the study. Of the patients, 5.2% had AT with 25% of cases persisting to the next time point, while 17.1% of patients had RT of which 65.3% persisted. When tremor data were examined in individual patients, they often had periods of tremor interspersed with periods of no tremor.Having RT was associated with age (OR=1.07 per year; 95% confidence interval 1.03–1.11), sex (OR=0.17 for males; 0.05–0.78), cocaine use (OR=10.53; 2.22–49.94), dyskinesia (OR=0.90; 0.83–0.97), and bradykinesia (OR=1.16; 1.09–1.22). Developing RT was strongly associated with previous measurement RT (OR=9.86; 3.80–25.63), with previous RT severity (OR=1.22; 1.05–1.41), and higher anticholinergic load (OR= 1.24; 1.08–1.43).Having AT was associated with tremor-inducing medication (OR= 4.54; 1.90–10.86), cocaine use (OR=14.04; 2.38–82.96), and bradykinesia (OR=1.07; 1.01–1.15). Developing AT was associated with, previous AT severity (OR=2.62 per unit; 1.64–4.18) and tremor reducing medication (OR=0.08; 0.01–0.55).ConclusionsLong-stay SMI patients are prone to developing tremors, which show a relapsing–remitting course. Differentiation between RT and AT is important as risk factors differ and they require different prevention and treatment strategies.

Parkinson subtype-specific Granger-causal coupling and coherence frequency in the subthalamic area

Previous work on Parkinson’s disease (PD) has indicated a predominantly afferent coupling between affected arm muscle activity and electrophysiological activity within the subthalamic nucleus (STN). So far, no information is available indicating which frequency components drive the afferent information flow in PD patients. Non-directional coupling e.g. by measuring coherence is primarily established in the beta band as well as at tremor frequency. Based on previous evidence it is likely that different subtypes of the disease are associated with different connectivity patterns. Therefore, we determined coherence and causality between local field potentials (LFPs) in the STN and surface electromyograms (EMGs) from the contralateral arm in 18 akinetic-rigid (AR) PD patients and 8 tremor-dominant (TD) PD patients. During the intraoperative recording, patients were asked to lift their forearm contralateral to the recording side. Significantly more afferent connections were detected for the TD patients for tremor-periods and non-tremor-periods combined as well as for only tremor periods. Within the STN 74% and 63% of the afferent connections are associated with coherence from 4–8Hz and 8–12Hz, respectively. However, when considering only tremor-periods significantly more afferent than efferent connections were associated with coherence from 12 to 20Hz across all recording heights. No difference between efferent and afferent connections is seen in the frequency range from 4 to 12Hz for all recording heights. For the AR patients, no significant difference in afferent and efferent connections within the STN was found for the different frequency bands. Still, for the AR patients dorsal of the STN significantly more afferent than efferent connections were associated with coherence in the frequency range from 12 to 16Hz. These results provide further evidence for the differential pathological oscillations and pathways present in AR and TD Parkinson patients.

Estimation of the phase response curve from Parkinsonian tremor.

Phase response curves (PRCs), characterizing the response of an oscillator to weak external perturbation, have been estimated from a broad range of biological oscillators, including single neurons in vivo. PRC estimates, in turn, provide an intuitive insight into how oscillatory systems become entrained and how they can be desynchronized. Here, we explore the application of PRC theory to the case of Parkinsonian tremor. Initial attempts to establish a causal effect of subthreshold transcranial magnetic stimulation applied to primary motor cortex on the filtered tremor phase were unsuccessful. We explored the possible explanations of this and demonstrate that assumptions made when estimating the PRC in a traditional setting, such as a single neuron, are not arbitrary when applied to the case of tremor PRC estimation. We go on to extract the PRC of Parkinsonian tremor using an iterative method that requires varying the definition of the tremor cycle and estimating the PRC at multiple peristimulus time samples. Justification for this method is supported by estimates of PRC from simulated single neuron data. We provide an approach to estimating confidence limits for tremor PRC and discuss the interpretational caveats introduced by tremor harmonics and the intrinsic variability of the tremor's period.

Low‐frequency earthquakes reveal punctuated slow slip on the deep extent of the Alpine Fault, New Zealand

AbstractWe present the first evidence of low‐frequency earthquakes (LFEs) associated with the deep extension of the transpressional Alpine Fault beneath the central Southern Alps of New Zealand. Our database comprises a temporally continuous 36 month‐long catalog of 8760 LFEs within 14 families. To generate this catalog, we first identify 14 primary template LFEs within known periods of seismic tremor and use these templates to detect similar events in an iterative stacking and cross‐correlation routine. The hypocentres of 12 of the 14 LFE families lie within 10 km of the inferred location of the Alpine Fault at depths of approximately 20–30 km, in a zone of high P‐wave attenuation, low P‐wave speeds, and high seismic reflectivity. The LFE catalog consists of persistent, discrete events punctuated by swarm‐like bursts of activity associated with previously and newly identified tremor periods. The magnitudes of the LFEs range between ML – 0.8 and ML 1.8, with an average of ML 0.5. We find that the frequency‐magnitude distribution of the LFE catalog both as a whole and within individual families is not consistent with a power law, but that individual families' frequency‐amplitude distributions approximate an exponential relationship, suggestive of a characteristic length‐scale of failure. We interpret this LFE activity to represent quasi‐continuous slip on the deep extent of the Alpine Fault, with LFEs highlighting asperities within an otherwise steadily creeping region of the fault.

Volcanic tremors and magma wagging: gas flux interactions and forcing mechanism

Volcanic tremor is an important precursor to explosive eruptions and is ubiquitous across most silicic volcanic systems. Oscillations can persist for days and occur in a remarkably narrow frequency band (i.e. 0.5–7 Hz). The recently proposed magma-wagging model of Jellinek & Bercovici provides a basic explanation for the emergence and frequency evolution of tremor that is consistent with observations of many active silicic and andesitic volcanic systems. This model builds on work suggesting that the magma column rising in the volcanic conduit is surrounded by a permeable vesicular annulus of sheared bubbles. The magma-wagging model stipulates that the magma column rattles within the spring like foam of the annulus, and predicts oscillations at the range of observed tremor frequencies for a wide variety of volcanic environments. However, the viscous resistance of the magma column attenuates the oscillations and thus a forcing mechanism is required. Here we provide further development of the magma-wagging model and demonstrate that it implicitly has the requisite forcing to excite wagging behaviour. In particular, the extended model allows for gas flux through the annulus, which interacts with the wagging displacements and induces a Bernoulli effect that amplifies the oscillations. This effect leads to an instability involving growing oscillations at the lower end of the tremor frequency spectrum, and that drives the system against viscous damping of the wagging magma column. The fully non-linear model displays tremor oscillations associated with pulses in gas flux, analogous to observations of audible ‘chugging’. These oscillations also occur in clusters or envelopes that are consistent with observations of sporadic tremor envelopes. The wagging model further accurately predicts that seismic signals on opposite sides of a volcano are out of phase by approximately half a wagging or tremor period. Finally, peaks in gas flux occur at the end of the growing instability several tens of seconds after the largest tremors, which is consistent with observations of a 30- to 50-s lag between major tremor activity and maximum gas release. The extended magma-wagging model, thus, predicts tremor frequency and its evolution before and during an eruption, as well as a driving mechanism to keep the tremor excited for long periods.

The causal relationship between subcortical local field potential oscillations and Parkinsonian resting tremor

To study the dynamical mechanism which generates Parkinsonian resting tremor, we apply coupling directionality analysis to local field potentials (LFP) and accelerometer signals recorded in an ensemble of 48 tremor epochs in four Parkinsonian patients with depth electrodes implanted in the ventro-intermediate nucleus of the thalamus (VIM) or the subthalmic nucleus (STN). Apart from the traditional linear Granger causality method we use two nonlinear techniques: phase dynamics modelling and nonlinear Granger causality. We detect a bidirectional coupling between the subcortical (VIM or STN) oscillation and the tremor, in the theta range (around 5 Hz) as well as broadband (>2 Hz). In particular, we show that the theta band LFP oscillations definitely play an efferent role in tremor generation, while beta band LFP oscillations might additionally contribute. The brain→tremor driving is a complex, nonlinear mechanism, which is reliably detected with the two nonlinear techniques only. In contrast, the tremor→brain driving is detected with any of the techniques including the linear one, though the latter is less sensitive. The phase dynamics modelling (applied to theta band oscillations) consistently reveals a long delay in the order of 1–2 mean tremor periods for the brain→tremor driving and a small delay, compatible with the neural transmission time, for the proprioceptive feedback. Granger causality estimation (applied to broadband signals) does not provide reliable estimates of the delay times, but is even more sensitive to detect the brain→tremor influence than the phase dynamics modelling.

Magnetic signatures associated with magma ascent and stagnation at Popocatepetl volcano, Mexico, during 2006

Abstract Monitoring of real-time magnetic signals at Popocatepetl during 2006 has allowed discrimination of magma injection and dome growth. Magnetic signals correlated with seismic, volcanotectonic events and harmonic tremor, as well as number of small emissions, spring water pH, ash components and dome evolution helped define upward magma transport and yield a better understanding of the volcanic plumbing system. Magma ascent occurs mostly in periods of 7±3 days associated with harmonic tremor and decreasing magnetic signals between −1.1 and −15 nT, followed by increasing signals linked to cooling of the domes and increased seismicity over periods of 1 to more than 3 months. The dome clogs the vent after the negative magnetic anomaly–harmonic tremor period associated with magma ascent and forces an explosive crater-reopening explosion. Larger negative changes in the magnetic signals occurred in April (−6 nT), August (−3 to −6 nT) and October to December (−5 to −15 nT), associated with dome formation and growth. Negative magnetic anomalies preceded eruptions by 3 days in 2006.

Firing Patterns and Correlations of Spontaneous Discharge of Pallidal Neurons in the Normal and the Tremulous 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Vervet Model of Parkinsonism

To investigate the role of the basal ganglia in parkinsonian tremor, we recorded hand tremor and simultaneous activity of several neurons in the external and internal segments of the globus pallidus (GPe and GPi) in two vervet monkeys, before and after systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and development of parkinsonism with tremor of 5 and 11 Hz. In healthy monkeys, only 11% (20/174) of the GPe cells and 3% (1/29) of the GPi cells displayed significant 3-19 Hz oscillations. After MPTP treatment, 39% (107/271) of the GPe cells and 43% (26/61) of the GPi cells developed significant oscillations. Oscillation frequencies of single cells after MPTP treatment were bimodally distributed around 7 and 13 Hz. For 10% of the oscillatory cells that were recorded during tremor periods, there was a significant tendency for the tremor and neuronal oscillations to appear simultaneously. Cross-correlation analysis revealed a very low level of correlated activity between pallidal neurons in the normal state; 95.6% (477/499) of the pairs were not correlated, and oscillatory cross-correlograms were found in only 1% (5/499) of the pairs. After MPTP treatment, the correlations increased dramatically, and 40% (432/1080) of the cross-correlograms had significant oscillations, centered around 13-14 Hz. Phase shifts of the cross-correlograms of GPe pairs, but not of GPi, were clustered around 0 degrees. The results illustrate that MPTP treatment changes the pattern of activity and synchronization in the GPe and GPi. These changes are related to the symptoms of Parkinson's disease and especially to the parkinsonian tremor.

Evidence that ventrolateral thalamotomy may eliminate the supraspinal component of both pathological and physiological tremors.

Ventrolateral (VL) thalamotomy produced a marked reduction of oscillations related to the supraspinal components of Parkinson's disease tremor (4-7 Hz) and physiological tremor (8-12 Hz). Finger tremor was examined in nine patients undergoing unilateral VL thalamotomy and in nine age-matched controls. In comparison to the preoperative state, the relative percentage of power within the 7.6-12.5 Hz band did not increase after the surgical procedure. Furthermore, the amount of absolute power within the 7.6-12.5 Hz band was much lower for post-surgical patients in comparison to matched controls when periods of tremor having equal amplitudes were compared. These results suggest that VL thalamotomy interrupts a common circuit involved in the supraspinal component of both physiological and pathological tremors. We provide evidence that the thalamus may be involved in circuits generating physiological tremor in humans.

Voluntary motor reactions: does stimulus appearance prolong the actual tremor period?

Entrainment of voluntary motor responses by ongoing tremors demonstrates the interaction of motor actions simultaneously performed by the same muscle. In the case of physiological tremor, based on experimental data, Kogan (Determining the influence of a bright stimulus on the ultramicrostructure of the movement control process in highly qualified wrestlers, Tesisi 7, Nautschno-metoditscheskoi konferenzii respublik Pribaltiki i Belorussi po woprosam sportivnoi trenirovki, Riga, 1978:56–57) postulated a direct and immediate impact of a `go' stimulus on the actual tremor cycle. This paper represents a critical replication of this investigation, showing that the effect reported can be simply explained as an inherent statistical consequence of the experimental paradigm.

Rapid wrist movements in patients with essential tremor. The critical role of the second agonist burst.

Ballistic wrist flexion movements towards 15, 30 and 60 degrees visual targets were studied in a group of 17 patients with hereditary essential tremor. Compared with age-matched normal subjects (n = 16), there were three main kinematic differences: patients overshot the target a little more; the kinematic profile of their movements was more 'asymmetric' due to higher peak decelerations; and their movements initiated tremor. Ballistic movements performed by patients with essential tremor were associated with a triphasic pattern of agonist-antagonist-agonist muscle activity similar to that of normal subjects. The duration and size of each EMG burst was normal. The onset latency of the antagonist EMG burst was also normal, but the onset of the second agonist EMG burst was delayed. The delay in the onset of the second agonist EMG activity resulted in unopposed action of the antagonist muscle in the second half of each movement. As a result, deceleration occurred too rapidly as the hand returned past the target leading to a series of damped oscillations around the point of aim. The onset latency of the second agonist EMG burst correlated significantly with the tremor period; the longer the period the later the burst. We speculate that the delay in the second agonist burst reflects an abnormality in the timing of anticipatory muscle activity in essential tremor and that this may involve cerebellar mechanisms.

Uniform frequency of parkinsonian resting tremor in the lips, jaw, tongue, and index finger

Parkinsonian resting tremor was examined in the lips, jaw, tongue, and index finger using electromyography (EMG) and displacement transduction. Long-term spectral averaging of tremor movement and EMG signals revealed that resting tremor frequencies were remarkably uniform across these orofacial and hand structures within the same parkinsonian subjects. However, marked variability in tremor spectral amplitude across structures and subtle moment-to-moment variations in tremor period, amplitude, and waveform shape were also observed. Although these observations argue for a central source of tremor, it appears that interactive central and/or peripheral neural circuitry may yield variations in tremor characteristics.

Slow waves trapped in a fluid‐filled infinite crack: Implication for volcanic tremor

The dynamics and seismic radiation of fluid‐filled cracks have been studied by numerous authors, as models for tremor and for long‐period events observed at volcanoes. One of the most intriguing results of the recent models is the existence of a very slow wave propagating along the crack boundary. In order to better understand this slow wave, which has so far only been studied numerically, we studied analytically normal modes trapped in a liquid layer sandwiched between two solid half‐space. A slow wave, similar to the tube wave found by Biot, exists for all wavelengths. In the short wavelength limit, this wave approaches the Stoneley wave for the liquid‐solid interface. Unlike the tube wave, however, as the wavelength increases to infinity, both the phase and group velocities approach zero, in inverse proportion to the square root of wavelength. The phase velocity and amplitude of this slow wave are in good agreement with those obtained by the numerical studies on the dynamics of fluid‐filled cracks by two dimensional and three‐dimensional finite difference methods. In the past the size of a magma body has been estimated from volcanic tremor periods and the acoustic velocity in the fluid. These estimates should be drastically reduced if the slow wave dominates the tremor. For example, the extremely long‐period volcanic tremor, with periods up to 7s, observed at Mount Aso may be generated by a fluid‐filled crack of modest size, a magma body 0.5 m thick and 0.5 km long.

Observations of volcanic tremor at Mount St. Helens in April and May 1980

Abstract High-amplitude, nearly monochromatic volcanic tremor was observed before, during, and after the 18 May 1980 eruption of Mount St. Helens. The tremor often remained stationary for periods of several minutes or more. For the period before and immediately following the main eruption, spectra calculated from three-component seismograms contained a nearly constant dominant frequency of 1.1 to 1.5 Hz. This contrasts with a dominant frequency of 1.7 to 2.1 Hz calculated for the tremor associated with the 25 May eruption. Amplitude decay with distance obeys the form A ∼ r n , where A is the tremor amplitude and r is the observation distance from the source. The exponent n , was determined in a least-squares sense to be −1.5 ± 0.4, −1.5 ± 0.3, and −1.7 ± 0.3, before and shortly after the main eruption on 18 May 1980 and 24 May 1980, respectively. The exponent for low-frequency volcanic earthquakes before the main eruption was −1.6 ± 0.3, a value similar to that of the volcanic tremor and suggests that the source of the volcanic tremor is shallow as is the source of the low-frequency earthquakes. The spectra of the tremor periods are very similar to those of the low-frequency volcanic earthquakes. There are cases where volcanic tremor appears as a continuation of a low-frequency earthquake. These observations suggest that the volcanic tremor and the low-frequency volcanic earthquakes are strongly interconnected and indeed may well share a common source mechanism. Based on both signal stationarity and spectral amplitude decay consistency, we suggest, in common with others, that the monochromatic nature of volcanic tremor is mainly due to a source effect, while the path and station effects are relatively minor. The tremor amplitude changes as a result of variations in the source driving force. The frequency shift for the 24 May 1980 tremor may be due to a source dimension change .

Deep volcanic tremor and magma ascent mechanism under Kilauea, Hawaii

Deep harmonic tremor originating at depths around 40 km under Kilauea was studied using records accumulated since 1962 at the Hawaii Volcano Observatory of the U.S. Geological Survey. The deep source of the tremor was determined by onset times and confirmed by the relative amplitude across the island‐wide network of seismometers. The period of tremor was conclusively shown to be determined by the source effect and not by the path or station site effect because the period would change considerably in time but maintained uniformity across the seismic net during the tremor episode. The tremor appeared to be primarily composed of P waves. We interpret the observed period and amplitude in terms of the stationary crack model of Aki et al. (1977) and find that the seismic moment rates for deep tremors are considerably larger than those for shallow‐tremors suggesting more vigorous transport for the former. We propose a kinematic source model which may be more appropriate for deep tremor. According to this model, a measurable quantity called ‘reduced displacement’ is directly proportional to the rate of magma flow. A systematic search for deep tremor episodes was made for the period from 1962 through 1979, and the amplitude, period, and duration of the tremor were tabulated. We then constructed a cumulative reduced‐displacement plot over the 18‐year period. The result shows a generally steady process which does not seem to be significantly affected by major eruptions and large earthquakes near the surface. The total magma flow estimated from the reduced displacement is however, one order of magnitude smaller than that estimated by Swanson (1972). It may be that most channels transport magma aseismically, and only those with strong barriers generate tremor.

Source mechanism of volcanic tremor: fluid-driven crack models and their application to the 1963 kilauea eruption

We propose a model for the mechanism of magma transport based on a fluid-filled tensile crack driven by the excess pressure of fluid. Such a transport mechanism can generate seismic waves by a succession of jerky crack extensions, if the fracture strength of rock varies in space, or if there is a difference between the dynamic and static values of the critical stress intensity factor. We also find that the opening and closing of a narrow channel connecting two fluid-filled cracks may be a source of seismic waves. Using the finite-difference method, we calculated the vibration of dry and fluid-filled cracks generated by: (1) a jerky extension at one end or at both ends and (2) a jerky opening of a narrow channel connecting two cracks. We then calculated the far-field and near-field radiation from these vibrating cracks. The spectra show peaked structures, but interestingly, most high-frequency peaks are only present in the near-field and cannot be transmitted to the far-field. The spectral features described above are often observed for volcanic tremors and in some cases for seismic signals associated with hydraulic fracturing experiments. We first consider as a model of volcanic tremor randomly occurring jerky crack extensions, and derive a formula relating the tremor amplitude to the excess pressure in the magma, the incremental area in each extension, and the frequency of extensions. These parameters are also constrained by other observations, such as the rate of magma flow. Our model was tested quantitatively against observations made in one of the best-described case histories of volcanic tremor: the October 5–6, 1963 Kilauea flank eruption. We found that a single, long crack extending from the summit to the eruptive site cannot explain the observations. The model of a steadily expanding crack ran into difficulties when quantitative comparisons were made with observations. The extension of crack area needed to explain the amplitude of volcanic tremor should accompany a large increase in tremor period which was not observed. Our second model is a chain of cracks connected by narrow channels which open and close. The length of each crack is around 1 km, the channel area connecting neighboring cracks is about 10 3m 2, and the channel opens jerkily with the magmatic excess pressure of about 20 bars. The frequency of jerky opening of each channel is about once in 15 seconds. The channel is closed after each jerky opening, as soon as magma is moved through the channel.

The Relevance of the So-Called Tremor for the Control of Voluntary Movement

The force a man exerts when moving a mass, contains discontinuities - the so-called tremor - which occur periodically every 100 - 120 milliseconds. It is concluded, that the tremor is due to a synchronuous innervation of muscle fibers. Further biological movement control systems are stable only if the contraction times of the muscle fibers envolved are shorter than one-half the tremor period. Only the fast (twitch) fibers with contraction times shorter than 60 milliseconds can meet this condition. The slow muscle fibers may be part of a second control loop which lies in parallel to the fast one.