Although Essential Tremor (ET) is the most common type of tremor, many patients are left without satisfactory treatment options. One potential alternative treatment to medication or surgery is a wearable tremor-suppressing device. However, optimizing the effectiveness of such a device requires knowledge of which muscles/joints are most responsible for tremor. To answer this question, current efforts simulate tremor propagation using a model of the neuromusculoskeletal dynamics of the upper limb. To guide efforts to identify realistic model parameters and use the model to determine the mechanical origin of tremor, we performed preliminary parameter estimation work and a thorough sensitivity analysis of this tremor propagation model. The tremor propagation model included muscle activation inputs to the 15 major superficial muscles and joint displacement outputs in the 7 main degrees of freedom (DOF) from the shoulder to the wrist, resulting in 105 input-output relationships. We calculated the mean normalized sensitivities of all outputs to all 107 model parameters over the tremor band (4 to 8 Hz), resulting in approximately 12,000 sensitivities. We found that sensitivities were relatively constant in the tremor band, except for shoulder adduction-abduction, which exhibited a large peak in sensitivity between 4 and 5 Hz. Averaged across the tremor band, the system was most sensitive to select elements of inertia, muscle force, muscle moment arm, damping, muscle time constants, and stiffness (in that order). The 19 highest all-input-excitation sensitivities were between 1.2 and 4.57, meaning a 100% change in parameter value produces 120-457% change in tremor. Conversely, the model includes many parameters to which the outputs are relatively insensitive. For example, the sensitivities to almost one third of the 107 parameters are below 0.1, meaning a 100% change in parameter value produces only a 10% change in tremor. To gain additional insight, we compared the sensitivities of the full model to those of a simpler model including only two inputs and two outputs. Analyzing the two-input two-output model revealed patterns in sensitivity which persist in the full model. The sensitivities of the full model were further compared to past studies that performed rudimentary sensitivity analyses and were found to match while adding significantly more parameter-specific sensitivity information. Future work will extend this sensitivity analysis to tremor at the hand, where it matters most.

Tremor affects millions of people and many patients desire alternative treatment options to medication or neural surgery. Peripheral suppression techniques are gaining greater use, but are currently applied in a trial-and-error method. To optimize these techniques, the muscles most responsible for an individual patient's tremor need to be identified. In this dissertation, I explored two parallel paths that both could aid in identifying muscles responsible for tremor. The first method utilizies measured data and a technique (coherence) that quantifies the frequency dependent correlation between two signals. Using coherence to identify muscles contributing to tremor requires at least two parts: an analysis of how tremor content is shared between muscles, and an analyis between muscle activity and joint/hand motion. The interpretation of the second analysis depends on the results of the first. The second method of identifying responsible muscles uses a mathematical model of the upper limb. With a validated model established techniques can be used to quantify the contribution to the output from each input. However, the accuracy of the model that has been previously used in the Neuromechanics Research Group had not been quantified. To evaluate the accuracy of this model, I used measured muscle activity as the input to generate simulated tremor and compared that to the measured tremor. From the first method, I found that synergistic muscles tend to share tremor content and do so in phase with each other. Therefore, tremor is likely due to a group of muscles rather than a single muscle. Additionally, I observed that the elbow flexor and wrist extensor muscles tended to be most correlated with tremor and should therefore be considered in peripheral suppression techniques. The second method revealed that while this upper-limb model shows potential to predict cases of severe tremor, improved model parameters must be identified through measurement or estimation techniques before the model should be used as it currently over-predicts the tremor.

Deep non-volcanic tremor is a newly discovered seismic phenomenon with low amplitude, long duration, and no clear P- and S-waves as compared with regular earthquake. Tremor has been observed at many major plate-boundary faults, providing new information about fault slip behaviors below the seismogenic zone. While tremor mostly occurs spontaneously (ambient tremor) or during episodic slow- slip events (SSEs), sometimes tremor can also be triggered during teleseismic waves of distance earthquakes, which is known as "triggered tremor". The primary focus of my Ph.D. work is to understand the physical mechanisms and necessary conditions of triggered tremor by systematic investigations in different tectonic regions. These include Taiwan, California, southwest Japan, Alaska and the Aleutian Arc, Cascadia, and New Zealand. In the first chapter of my dissertation, I conduct a systematic survey of triggered tremor beneath the Central Range (CR) in Taiwan for 45 teleseismic earthquakes from 1998 to 2009 with Mw ≥ 7.5. Triggered tremors are visually identified as bursts of high-frequency (2-8 Hz), non-impulsive, and long-duration seismic energy that are coherent among many seismic stations and modulated by the teleseismic surface waves. A total of 9 teleseismic earthquakes has triggered clear tremor in Taiwan. The peak ground velocity (PGV) of teleseismic surface waves is the most important factor in determining tremor triggering potential, with an apparent threshold of ~0.1 cm/s, or 7-8 kPa. However, such threshold is partially controlled by the background noise level, preventing triggered tremor with weaker amplitude from being observed. In addition, I find a positive correlation between the PGV and the triggered tremor amplitude, which is consistent with the prediction of the 'clock-advance' model. This suggests that triggered tremor can be considered as a sped-up occurrence of ambient tremor under fast loading from the passing surface waves. Finally, the incident angles of surface waves also play an important rule in controlling the tremor triggering potential. The next chapter focuses on a systematic comparison of triggered tremor around the Calaveras Fault (CF) in northern California (NC), the Parkfield-Cholame section of the San Andreas Fault (SAF) in central California (CC), and the San Jacinto Fault (SJF) in southern California (SC). Out of 42 large (Mw ≥7.5) earthquakes between 2001 and 2010, only the 2002 Mw 7.9 Denali fault earthquake triggered clear tremor in NC and SC. In comparison, abundant triggered and ambient tremor has been observed in CC. Further analysis reveal that the lack of triggered tremor observations in SC and NC is not simply a consequence of their different background noise levels as compared to CC, but rather reflects different background tremor rates in these regions. In the final chapter, I systematically search for triggered tremor following the 2011 Mw9.0 Tohoku-Oki earthquake in the regions where ambient or triggered tremor has been found before. The main purpose is to check whether triggered tremor is observed in regions when certain conditions (e.g., surface wave amplitudes) are met. Triggered tremor is observed in southwest Japan, Taiwan, the Aleutian Arc, south-central Alaska, northern Vancouver Island, the Parkfield-Cholame section of the SAF in CC and the SJF in SC, and the North Island of New Zealand. Such a widespread triggering of tremor is not too surprising because of the large amplitude surface waves (minimum peak value of ~0.1 cm/s) and the associated dynamic stresses (at least ~7-8 kPa), which is one of the most important factors in controlling the triggering threshold. The triggered tremor in different region is located close to or nearby the ambient tremor active area. In addition, the amplitudes of triggered tremor have positive correlations with the amplitudes of teleseismic surface waves among many regions. Moreover, both Love and Rayleigh waves participate in triggering tremor in different regions, and their triggering potential is somewhat controlled by the incident angles. In summary, systematically surveys of triggered tremor in different tectonic regions reveal that triggered tremor shares similar physical mechanism (shear failure on the fault interface) as ambient tremor but with different loading conditions. The amplitude of the teleseismic surface wave is one of the most important factors in controlling the tremor triggering threshold. In addition, the frequency contents and incident angles of the triggering waves, and local fault geometry and ambient conditions also play certain roles in determining the triggering potential. On the other hand, the background noise level and seismic network coverage and station quality also could affect the apparent triggering threshold. Because triggered tremor occurs almost instantaneously during the teleseismic surface waves, and the tremor amplitude is somewhat controlled by the amplitude of the triggering waves, the occurrence time and the size of the triggered tremor could be somewhat predictable, so long as we know the amplitude and period of surface waves and associated time-varying dynamic stresses. Hence, further analysis of triggered tremor may provide important new clues on the nucleation and predictability of seismic events.

Modulation of voice is a result of physiologic oscillation within one or more components of the vocal system including the breathing apparatus (i.e., pressure supply), the larynx (i.e. sound source), and the vocal tract (i.e., sound filter). These oscillations may be caused by pathological tremor associated with neurological disorders like essential tremor or by volitional production of vibrato in singers. Because the acoustical characteristics of voice modulation specific to each component of the vocal system and the effect of these characteristics on perception are not well-understood, it is difficult to assess individuals with vocal tremor and to determine the most effective interventions for reducing the perceptual severity of the disorder. The purpose of the present studies was to determine how the acoustical characteristics associated with laryngeal-based vocal tremor affect the perception of the magnitude of voice modulation, and to determine if adjustments could be made to the voice source and vocal tract filter to alter the acoustic output and reduce the perception of modulation. This research was carried out using both a computational model of speech production and trained singers producing vibrato to simulate laryngeal-based vocal tremor with different voice source characteristics (i.e., vocal fold length and degree of vocal fold adduction) and different vocal tract filter characteristics (i.e., vowel shapes). It was expected that, by making adjustments to the voice source and vocal tract filter that reduce the amplitude of the higher harmonics, the perception of magnitude of voice modulation would be reduced. The results of this study revealed that listeners' perception of the magnitude of modulation of voice was affected by the degree of vocal fold adduction and the vocal tract shape with the computational model, but only by the vocal quality (corresponding to the degree of vocal fold adduction) with the female singer. Based on regression analyses, listeners' judgments were predicted by modulation information in both low and high frequency bands. The findings from these studies indicate that production of a breathy vocal quality might be a useful compensatory strategy for reducing the perceptual severity of modulation of voice for individuals with tremor affecting the larynx.

Objectives: Determine the effect of contraction type and intensity, inertial loading, and visual feedback on various measures of hand tremor in subjects with essential tremor. Methods: Study 1. Twenty-three ET subjects and 22 controls held their hand in an outstretched position while supporting various submaximal loads (no-load, 5%, 15% and 25% 1-repetition maximum). Hand postural tremor and wrist extensor neuromuscular activity (EMG) were recorded. Study 2. Twenty-one ET subjects and 22 controls applied isometric wrist extension contractions with and without visual feedback. Various submaximal contraction intensities were evaluated (5%, 10%, 20% and 30% MVC). Force production and EMG were recorded. Study 3. Twenty-one ET subjects and 22 healthy controls performed slow wrist extension-flexion movements while supporting various submaximal loads (no-load, 5%, 15% and 25% 1-repetition maximum). Angular displacement and EMG were recorded. Results: Study 1. Inertial loading resulted in a reduction in postural tremor in ET subjects. The largest reduction in tremor amplitude occurred at the 15% load, which was associated with spectral separation of the mechanical reflex and central tremor component. Despite an increase in overall neuromuscular activity with inertial loading, EMG tremor power did not increase with loading. Study 2. Higher contraction intensities were associated with larger amplitude force fluctuations and greater EMG amplitudes. Tremor spectral power of force and EMG remained constant at all target intensities, resulting in a reduction in relative tremor power at higher contraction intensities. Visual feedback affected subjects in the control and ET groups similarly. Study 3. Subjects with more pronounced tremor spectral peaks had larger amplitude kinetic tremor, which was reduced with inertial loading. Despite an increase in overall neuromuscular activity with inertial loading, EMG tremor spectral power was only slightly increased with loading, which resulted in a large reduction in relative EMG tremor power. Conclusions: The effect of inertial loading on postural and kinetic tremor amplitude appears to be mediated in large part by its effect on the interaction between the mechanical reflex and central tremor components. The level of motor unit entrainment remains relatively constant in subjects with ET despite increasing contraction intensities. / Thesis (Ph.D, Rehabilitation Science) -- Queen's University, 2008-10-24 11:18:57.537

Sammanfattning Bakgrund: Deep brain stimulation (DBS) i nucleus ventralis intermedius i thalamus (VIM) eller caudala zona incerta (cZi) ger goda effekter på tremorsymptomen för patienter med essentiell tremor. Patienterna som behandlats med DBS kan få bieffekter som i vissa fall leder till talpåverkan, så kallad stimuleringsinducerad dysartri. Huruvida det finns risk för bieffekter som drabbar röstens funktion hos patienter med essentiell tremor saknas studier kring men man vet att grundsjukdomen kan påverka rösten akustiskt samt att vissa patienter utvecklar rösttremor. Att drabbas av en bieffekt efter DBS kan ha en inverkan på hur patienten subjektivt upplever resultatet av behandlingen.     Mål: Att undersöka om patienter med essentiell tremor som genomgått DBS subjektivt upplever någon form av röst- eller talbesvär jämfört med en frisk, ålders- och könsmatchad kontrollgrupp.   Metod: I studien deltog sammanlagt 42 deltagare varav 21 tillhörde en patientgrupp med essentiell tremor som genomgått DBS i cZi och de övriga 21 tillhörde en frisk, ålders- och könsmatchad kontrollgrupp. Deltagarna i de båda grupperna fick fylla i två formulär, RHI som berör röstens funktion och SOFT som berör talets funktion. Deltagarna som tillhörde patientgruppen fick också svara på fem fördjupande frågor om deras subjektiva upplevelse. Den statistiska signifikanstestningen genomfördes med avseende på om det fanns en skillnad i självskattningen mellan de båda grupperna.   Resultat: Resultaten i denna studie visade att patienterna med essentiell tremor s0m är behandlade med DBS skattar en signifikant större del subjektiva svårigheter av sin egen röst- och talfunktion jämfört med den friska kontrollgruppen.   Slutsats: Resultaten visade att det på gruppnivå finns signifikant större andel upplevda svårigheter relaterade till tal- och röstfunktionen hos patienter med essentiell tremor behandlade med DBS jämfört med en frisk kontrollgrupp. Resultaten visar även en stor individuell variation av den subjektiva upplevelsen av tal och röstpåverkan vilket är viktig information att delge patienter som ska genomgå DBS. Ett preoperativt samtal med logoped för information om möjliga bieffekter vid DBS och hur detta kan påverka patienten subjektivt är nödvändigt. De patienter som subjektivt upplever besvär med talet eller rösten bör erbjudas kontakt med logoped. / Abstract Background: Deep brain stimulation (DBS) of ventralis intermedius nucleus of thalamus (VIM) or caudala zona incerta (cZi) have been shown to be efficient in supressing tremor symptoms in patients with essential tremor. Patients who has been treated with DBS may acquire certain side effects of which in some cases results in an impact on the patients speech, known as stimulation- induced dysarthria. There is a lack of studies that investigate if there is a risk of side effects that is affecting voice functioning in patients with essential tremor. Previous studies have claimed that the disease itself may have an effect on the voice acoustics and that some patients develop voice tremor. The occurrence of a side effect caused by DBS may have an impact on the patients subjective experience of the treatment result.   Aim: To investigate whether patients with essential tremor treated with DBS are subjectively experiencing any form of voice or speech disability compared to a healthy, age and sex matched control group.   Method: The study included 42 participants all together whereof 21 was part of a patient group with essential tremor treated with DBS in cZi and the other 21 participants was part of a healthy, age and sex matched control group. The participants of both groups filled out two different forms, VHI (RHI) which affects voice function and SOFT which affects speech function. The participants in the patient group also answered five profound questions about their subjective experience. The test of statistical significance was performed with regard of if a difference was to be found in the self-ratings between the two groups.   Results: The results of the study show that patients with essential tremor whom have been treated with DBS rates a significantly greater amount of subjective difficulties related to the voice and speech functioning compared to the healthy control group.   Conclusion: The results show that the DBS-treated patients with essential tremor experience a significantly greater amount of subjective difficulties related to voice and speech functioning compared to a healthy control group. The results also show a great individual variety in the subjective experience of speech and voice function which is important information to notify patients who are due to undergo DBS-treatment. A preoperative meeting with a speech and language pathologist to be informed of possible side effects caused by the DBS and in what ways this can effect the patient subjectively is required. Patients who postoperatively experience a negative effect on speech or voice functioning should be offered contact with a speech and language pathologist. / Tal- och rösteffekter av djup hjärnstimulering hos patienter med ärftlig tremor

Made available in DSpace on 2015-12-06T23:46:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2006 / Objetivos: Embora compreenda a mais prevalente desordem do movimento, a fisiopatologia do tremor essencial (TE) e ainda controversa. Conforme a hipotese mais aceita, trata-se de um tremor central causado por uma disfuncao do complexo olivar inferior, provavelmente secundario a uma hipofuncao do sistema GABAergico. Vilela Filho et al (2001), por outro lado, relataram o caso de uma paciente com TE da mao direita que foi completamente eliminado apos uma isquemia restrita ao putamen posterior contralateral e sugeriram que o TE poderia representar a manifestacao clinica da hiperatividade do putamen posterior. O presente estudo foi realizado para testar essa hipotese no mais frequentemente usado modelo animal de TE, o tremor induzido pela harmalina em ratos e, empregando-se o mapeamento fisiologico por estimulacao, melhor determinar a organizacao somatotopica do striatum no rato. Metodos: 54 ratos Wistar machos (peso=250-350g) foram aleatoriamente distribuidos em tres grupos: experimental-GE (n=26), controle cirurgico-GCC (n=18) e controle farmacologico-GCF (n=10). Animais do GE foram submetidos a estriatotomia posterior estereotaxica unilateral (coordenadas: 1.8mm posterior/4.6mm lateral/5.85mm inferior; eletrodo: 0.35mm em diametro externo e 1.0mm de ponta exposta; parametros da lesao eletrolitica: 5.0mA/6o/60Hz) apos estimulacao eletrica do alvo (parametros: 0.2, 0.5, 1.0 e 2.0mA/monopolar/6o/60Hz). Nos animais do GCC, o eletrodo foi introduzido no alvo e retirado, sem se proceder a estimulacao ou lesao. Animais do GCF serviram apenas como controles para os efeitos da harmalina, nao tendo sido operados. Todos os animais (7o dia pos-operatorio naqueles operados) receberam harmalina intraperitonial (20mg/kg/ml), tendo sido o tremor induzido filmado 45 e 110 minutos apos sua administracao. A intensidade do tremor apendicular foi avaliada, independentemente, por um observador ocegoo, enquanto a dos tremores axiais, bem como a latencia e duracao de todos os tremores, pelos pesquisadores. Apos o teste da harmalina, os animais do GE e GCC foram sacrificados e seus cerebros enviados para o exame histopatologico. Resultados: Conforme criterios estabelecidos, 13 animais foram excluidos do estudo. O tremor apendicular mostrou-se reduzido ipsolateralmente a cirurgia em 20/21 animais do GE e em 2/9 do GCC e assimetrico em 1/10 do GCF; tais diferencas foram estatisticamente significantes entre GE e GCC e GE e GCF, mas nao entre GCC e GCF. Curiosamente, a latencia e duracao dos tremores axiais foram menores no GCF que no GE e GCC. A percentagem de reducao media do tremor apendicular foi 43.70%±14.22, tendo sido maior nas patas anteriores que posteriores e apos a estriatotomia posterior direita que esquerda. Lesoes estriatais laterais proporcionaram melhores resultados que as mediais. Conclusoes: Esses resultados sao sugestivos de uma provavel participacao do striatum posterior no tremor induzido pela harmalina em ratos e reforcam a hipotese determinante da realizacao do presente estudo. Os resultados derivados do mapeamento fisiologico estriatal por estimulacao e da resposta do tremor a cirurgia, por sua vez, sugerem a seguinte organizacao somatotopica no striatum dorsal do rato: patas dianteiras (muito provavelmente superpostas), posteriores e ventrais; tronco e cauda, anteriores; e patas traseiras, em posicao intermediaria entre as duas anteriores, anterior e dorsalmente as patas dianteiras, situando-se a contralateral posteriormente a ipsolateral / Purposes: Although the most prevalent movement disorder, the pathophysiology of essential tremor (ET) remains controversial. The most accepted hypothesis is that it is a central tremor caused by a dysfunction of the inferior olivary complex, probably secondary to GABAergic system malfunctioning. Evidence for the involvement of the basal ganglia had never been presented. Vilela Filho et al (2001), though, reported a case of a patient with unilateral hand ET which was completely relieved after a stroke restricted to the contralateral posterior putamen and suggested that ET could be the clinical manifestation of posterior putamen hyperactivity. The present study was designed to evaluate this hypothesis in the most used model of ET, harmaline-induced tremor in rats, and, by stimulation mapping, to better determine the somatotopic organization of the rat striatum. Methods: 54 male Wistar rats, 250-350g, were randomly distributed in three groups: experimental-EG (n=26), surgical control-SCG (n=18), and pharmacological control-PCG (n=10) groups. EG animals underwent stereotactic unilateral posterior striatotomy (coordinates: 1.8 posterior/4.6 lateral/5.85mm inferior; electrode: 0.35mm in external diameter and 1.0mm exposed tip; electrolytic lesion parameters: 0.5mA/6”/60Hz) after target stimulation (parameters: 0.2, 0.5, 1.0, and 2.0mA/monopolar/6”/60Hz). SCG rats underwent electrode placement at the target and withdrawn without stimulation or lesioning (sham lesion). PCG served exclusively as controls for harmaline effects. All animals received (7th postoperative day in those of EG and SCG) IP harmaline (20mg/kg/ml) and the induced-tremor was video recorded 45` and 110` after the injection. Limb tremor intensity was independently evaluated by a blind observer, while axial tremors intensity, as well as latency and duration of both limb and axial tremors, were evaluated by the researchers. Animals of EG and SCG were killed after harmaline test and their brains sent to histopathology. Results: Obeying predetermined criteria, 13 animals were excluded from the study. Limb tremor was reduced ipsolaterally to the operation in 20/21 rats of EG and in 2/9 of SCG, and was asymmetric in 1/10 of PCG. Comparisons between EG x SCG and EG x PCG were statistically significant, but not between SCG x PCG. None of the rats presented tremor reduction contralateral to the operation. Curiously, latency and duration of axial tremors, but not of limb tremor, were lesser in PCG than in EG and SCG. The mean percentage of limb tremor reduction in animals of EG was 43.7%±14.22, being greater in anterior than in posterior paws, and after right than left striatotomy. Lateral lesions yielded better results than medial lesions. Conclusions: These results suggest that the posterior striatum is possibly involved with harmaline-induced tremor in rats and give support to our hypothesis, according to which hyperactivity of the posterior putamen may play a role in the genesis of ET. Data provided by stimulation mapping and tremor response to operation suggest the following somatotopic organization in the rat dorsal striatum: forepaws (probably overlapped), caudal and ventral; trunk and tail, rostral; and hind paws, in an intermediary position, dorsal and rostral to the forepaws, being the contralateral one caudal to the ipsolateral. / BV UNIFESP: Teses e dissertações

Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Robotic-assisted surgery is a rapid growing field, facing challenging tasks and demands from surgeons, in particular in minimally invasive and microsurgery. However many of the present robotic systems are not well integrated in the surgical workflow, too big or too expensive. Micron is an innovative fully handheld active micromanipulator that helps surgeons to improve position accuracy and precision in microsurgery by cancelling the normal hand tremor. This thesis proposes an improvement and development of Micron, considering as target the stapedotomy procedure, microsurgery performed at the middle ear that aims to restore the hearing impairments. Two tools, a handle and a brace were designed and prototyped and the control was adapted; at the end the entire system was assessed through some experiments. Promising results were obtained in terms of tremor cancellation but further research is needed in order to reach clear advantages.

Optimized peripheral tremor suppression could address many limitations of surgical or medicinal treatments of Essential Tremor, however it is not well understood how the tremorogenic activity is distributed among the muscles of the upper limb, and therefore how to optimize such suppression. We recorded electromyographic (EMG) activity in the 15 major superficial muscles from the shoulder to the wrist while subjects performed postural and kinetic tasks similar to activities of daily living. We calculated the power spectral density and computed the total power in the tremor band (4"12 Hz) for each muscle, from which we determined the distribution of tremorogenic activity among the 15 muscles for various conditions. Differences in distribution between conditions were quantified as Pearson correlation coefficients. All 15 muscles exhibited some tremorogenic activity. The anterior deltoid exhibited by far the most power, the wrist extensors had more power than other distal muscles, and the triceps longus showed the least power. Distributions among muscles was highly consistent across repetitions (r = 0.91 ± 0.07) and somewhat stereotyped across subjects (r = 0.58 ± 0.31). Differences in task (postural vs. kinetic), limb configuration, and subject characteristics (sex; tremor severity, onset, and duration) had little effect on distribution (r =0.84). Interestingly, the distribution of tremorogenic activity was highly correlated (r = 0.94 ± 0.08) with the distribution of voluntary activity (power between 0.5 and 4 Hz). In particular, muscles opposing gravity had the highest amount of tremorogenic activity. This may explain in part why the distribution of tremorogenic activity was stereotyped across subjects.