Submitted by MARINA LOPES MECHLER null (mlopesvet@gmail.com) on 2018-02-19T14:08:06Z No. of bitstreams: 1 Dissertação_Marina Lopes Mechler.pdf: 2026984 bytes, checksum: ffc0d70577dd42d4b80d5ee121754dbd (MD5) / Approved for entry into archive by Alexandra Maria Donadon Lusser Segali null (alexmar@fcav.unesp.br) on 2018-02-20T12:49:32Z (GMT) No. of bitstreams: 1 mechler_ml_me_jabo.pdf: 2026984 bytes, checksum: ffc0d70577dd42d4b80d5ee121754dbd (MD5) / Made available in DSpace on 2018-02-20T12:49:32Z (GMT). No. of bitstreams: 1 mechler_ml_me_jabo.pdf: 2026984 bytes, checksum: ffc0d70577dd42d4b80d5ee121754dbd (MD5) Previous issue date: 2018-02-02 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O tremor congênito em suínos possui diversas etiologias, inclusive os pestivirus. O objetivo deste trabalho foi avaliar se o vírus da diarreia viral bovina (BVDV) é um dos agentes etiológicos da enfermidade. Para tal, foi realizada inoculação de dez fêmeas suínas gestantes com BVDV-2 em dois diferentes modelos experimentais, sendo o primeiro a inoculação oronasal das fêmeas (Grupo 1; n=4), e o segundo a inoculação fetal intrauterina (Grupo 2; n=4). O terceiro grupo (Grupo 3; n=2) foi o controle. As marrãs e os fetos foram desafiados aos 45 dias de gestação com BVDV-2. Foram colhidas amostras sangue de todos os leitões nascidos para obtenção de sangue total e soro, para determinação dos títulos de anticorpos pela virusneutralização (VN) e detecção de RNA viral pela técnica de RTPCR. Um terço dos neonatos foram eutanasiados ao terceiro dia de idade, e deles coletaram-se fragmentos de encéfalo, tronco encefálico e medula espinhal para avaliação anatomohistopatológica e RT-PCR. Os leitões que permaneceram vivos foram avaliados clinicamente todos os dias, e foi realizada colheita de sangue periodicamente durante 35 dias, as quais foram submetidas à sorologia (VN) e RTPCR. Os leitões de ambos os grupos não apresentaram sinais clínicos neurológicos e nasceram com ausência de vírus no sangue e nos órgãos. Os leitões do Grupo 1 não apresentaram anticorpos contra o BVDV-2 ao nascimento, que posteriormente foram adquiridos por transferência passiva materna. Ao contrário, os leitões do Grupo 2 nasceram com altos títulos de anticorpos contra o agente, que permaneceram altos até o término do período experimental. Microscopicamente, não foram observadas alterações dignas de nota. Macroscopicamente, observou-se que 29,5% do total de leitões abatidos dos grupos infectados nasceram com baixa relação entre cérebro e cerebelo, o que pode ser indicativo de hipoplasia cerebelar. Desta forma, concluiu-se que o BVDV não parece ser um agente etiológico para o tremor congênito suíno. / Congenital tremor in pigs has several etiologies, including pestiviruses. The objective of this study was to evaluate whether bovine viral diarrhea virus (BVDV) is one of the etiological agents of this disease. Ten pregnant gilts were inoculated with BVDV-2 in two different experimental models, the first being the oronasal inoculation of the females (group 1; n=4), and the second was the intrauterine fetal inoculation (group 2; n=4). The third group (group 3; n=2) constituted the control group. Gilts and fetuses were challenged at 45 days of gestation with strain BVDV-2 SV 280. Blood samples were collected from all piglets born to obtain whole blood and serum for determination of antibody titers by virus neutralization (VN) and detection of viral RNA by the RT-PCR technique. One third of the neonates were euthanized at the third day of age, and fragments of brain, cerebellum, brain stem and spinal cord were collected for anatomopathological and RT-PCR evaluation. The piglets that remained alive were clinically evaluated every day, and blood samples were collected periodically for 35 days, which were submitted to serology (VN) and RT-PCR. The piglets of both groups showed no clinical neurological signs and were born without virus in the blood and organs. Group 1 piglets did not present antibodies against BVDV-2 at birth, which were acquired by passive maternal transfer. In contrast, Group 2 piglets were born with high antibody titers against the agent, which remained high until the end of the experimental period. Microscopically, no noticeable changes were observed. Macroscopically, it was observed that 29.5% of the total piglets slaughtered from the infected groups were born with a low ratio between brain and cerebellum, which may be indicative of cerebellar hypoplasia. Thus, it was concluded that BVDV does not appear to be an etiological agent for congenital pig tremor. / 409435/2016-3 / 2016/02982-3,

No description available.

Parkinson's Disease affects more than 1 million people in the United States with 60,000 new cases being diagnosed each year. Currently, there is no cure for Parkinson's Disease, but there are several treatment options available. Currently the most popular surgical option is Deep Brain Stimulation. Microelectrode recording helps identify nuclei as the microelectrode passes through them. While the firing frequencies of the target nuclei are well defined, other nuclei are not. This study will attempt to characterize the Zona Incerta, which is the structure directly above the Subthalamic Nucleus, a target nucleus. Characterization of the firing frequency of the Zona Incerta will help aid Deep Brain Stimulation procedures. Looking at the Interspike Intervals for 25 files showed that the average firing frequency is 11.6Hz. A file recorded in the STN was used for comparison and to validate the methods used. This yielded an average firing frequency of 37.5Hz.

Parkinson’s disease and Essential tremor are the two most prevalent movement disorders in the world, but due to overlapping clinical symptoms, accurate differential diagnosis is difficult. As a result, approximately 60% of patients with movement disorders symptoms will have their diagnosis changed at least once before death. By their subjective nature, clinical exams are inherently imprecise, leading to the desire to create an objective, quantifiable test for movement disorders; a test that currently is elusive. Eye movements have been studied for a century, and are widely appreciated to be quantifiably affected in those with neurological disease. Through a collaborative effort between the VA hospital and VCU, over 1,000 movement disorder subjects had their eye movements recorded, utilizing an SR Research Eyelink 2. Patients with Parkinson’s disease exhibited an ocular gaze tremor during fixation, normal reflexive saccades, and reduced blink rate. Subjects with Essential tremor exhibited slowed saccadic dynamics, with increased latencies, in addition to a larger number of square wave jerk interruptions of otherwise stable fixation. After diagnostic features of each disorder were identified, prospective data collection could occur in a blinded fashion, and oculomotor features used to predict clinical diagnoses. It was determined that measures of fixation stability were capable of almost perfectly differentiating subjects with PD, and a novel, combined parameter was capable of similar results in ET. As a group, it appears as if these symptoms do not progress as the disease does, but subanalyses show that individual patients on constant pharmaceutical doses tracked over time do slightly change and progress. The near perfect separation of disease states suggest the ability of oculomotor recording to be a powerful biomarker to be used for the differential diagnosis of movement disorders. This tool could potentially impact and improve the lives of millions of people the world over.

Le tremblement, défini comme un mouvement rythmique involontaire, est un des mouvements anormaux les plus fréquents. Le tremblement n'est pas une pathologie mortelle, mais elle diminue souvent considérablement la qualité de vie de la personne. Les traitements efficaces ne sont pas encore disponibles, puisque les solutions pharmacologiques et chirurgicales souffrent encore de limitations en termes d'efficacité, de risques et de coûts. Une alternative consiste à utiliser des technologies d'assistance, tels que les exosquelettes ou la Stimulation Électrique Fonctionnelle (SEF).Néanmoins, la conception de systèmes actifs de compensation des tremblements présente plusieurs défis. Un tel système doit être capable, par exemple, d'atténuer les tremblements tout en minimisant la fatigue, la douleur et l'inconfort induit. Il doit aussi distinguer entre le tremblement et le mouvement volontaire, afin de réduire les interférences sur les mouvements intentionnels.Cette thèse se concentre donc sur l'évaluation de l'usage de la SEF pour atténuer le tremblement. Une première contribution concerne le développement des modèles neuromusculosquelettiques pour étudier l'influence des boucles réflexes sur la dynamique du tremblement, ainsi que la modulation de l'impédance de l'articulation via la co-contraction induite par la SEF. Un algorithme pour estimer en ligne le tremblement et ses caractéristiques tout en filtrant le mouvement volontaire a été proposé et validé sur patients. Enfin, un système SEF pour atténuer le tremblement basé sur le contrôle d'impédance a été conçu et évalué sur patients, alors qu'une deuxième stratégie en boucle fermée a été testée sur des sujets sains. / Tremor, defined as an involuntary, approximately rhythmic and roughly sinusoidal movement, is one of the most common movement disorders. It is not a life-threatening pathology, but it often decreases significantly the person's quality of life. Today, effective treatments for pathological tremor are not yet available, since current pharmacological and surgical alternatives still present limitations with respect to effectiveness, risks, and costs. A different approach is the use of assistive technologies, such as upper limb exoskeletons or Functional Electrical Stimulation (FES).Nevertheless, the design of active tremor compensation systems based on these technologies presents several challenges. Such a system must be able, for instance, to attenuate tremor while minimizing the induced fatigue, pain, and discomfort. Also, it must be able to distinguish between pathological tremor and voluntary motion, in order to reduce interference on intentional movements.This thesis is focused then in evaluating the use of FES to attenuate the effects of tremor. A first contribution concerns the use of neuromusculoskeletal models to study the effects reflex pathways may produce on tremor dynamics, as well as how FES-induced co-contraction may modulate joint impedance. Also, an online algorithm to estimate tremor and its features while simultaneously filtering voluntary motion has been proposed and validated with tremor patients. Finally, a FES system to attenuate tremor based on impedance control has been designed and evaluated on tremor patients, while a second strategy using closed-loop FES control has been tested on healthy subjects.

L’objectif général de cette thèse est d’étudier la production quantitative (i.e., nombre de mots) et qualitative (i.e. regroupements et alternances) du verbe d’action dans le vieillissement normal et dans les pathologies du mouvement à travers la tâche de fluence d’action, comparativement aux fluences classiques (i.e., sémantique et littérale). Nous avons montré que la production lors d’une tâche de fluence d’action est altérée chez des adultes âgés (60 ans et plus) comparativement à des adultes jeunes (30 ans et moins) et qu’elle est en lien avec les fonctions exécutives (Expérience 1) et la mémoire de travail (Expérience 3) chez l’adulte âgé. L’effet de l’âge paraît être modifié par le temps de production, les adultes âgés produisant moins de verbes d’action que les adultes jeunes pour un temps de trois minutes (Expérience 1) mais pas pour des temps d’une (Expérience 2) et de deux minutes (Expérience 3). De plus, les adultes âgés prenaient davantage en considération la consigne temporelle lors des tâches de fluence verbale que les adultes jeunes (Expérience 2). Les données d’une tâche d’association verbale (Expérience 4) indiquaient que les associations entre les noms et les verbes sont modifiées par l’âge. Nous avons comparés les performances de patients atteints de pathologiesdu mouvement à celles de participants contrôles lors de la tâche de fluence d’action. Nous avons montré que la production quantitative lors cette tâche est altérée chez des patients atteints de maladie de Parkinson (Expérience 5) et d’atrophie multisystématisée (Expérience 6). Dans le tremblement essentiel (Expérience 7), nous avons montré une atteinte de la fluence d’action alors que le traitement des verbes, lors d’une tâche de décision lexicale, n’était pas altéré. De plus, la chirurgie (stimulation cérébrale profonde) modifiait qualitativement la production dans la tâche de fluence d’action. Nos données montrent un impact du vieillissement normal et des pathologies du mouvement sur la production du verbe d’action, enraison de la nature fortement exécutive de ce processus. / The aim of this thesis is to investigate the production of action verbs through the action fluency task, in comparison to classical fluency tasks (i.e., semantic and letter). In first instance, production has been studied, both quantitatively and qualitatively, in aging. We have shown that action fluency is impacted by healthy aging and is related to executive functions (Experiment 1) and working memory (Experiment 3) in older adults. This effect of age appearsto be affected by production time, with older adults producing fewer action verbs than younger adults in three minutes (Experiment 1) but not in one (Experiment 2) and two minutes (Experiment 3). In addition, older adults took more into account the time instruction during verbal fluency tasks (Experiment 2). The verbal association task’s data (Experiment 4) indicated that associations between nouns and verbs are modified by age. In second instance,the production of action verbs has been studied within movement disorders. We have shown that the production in the action fluency task and the adaptation to time instruction are impacted by Parkinson's disease (Experiment 5). We have also shown that action fluency is altered within an atypical parkinsonism, multiple system atrophy (Experiment 6). In essential tremor (Experiment 7), we have shown an impairment of action fluency while verbs treatment, in a lexical decision task, was not altered. In addition, surgery (deep brain stimulation) qualitatively modified the production of verbs in action fluency. Our data highlight the impact of healthy aging and movement disorders on the production of action verb, due to the highly executive nature of this process.

Le système visuel humain est complexe par son organisation anatomique et par son fonctionnement incomplètement élucidé. Il est fonctionnellement divisé en deux systèmes. Le premier système est destiné à la vision consciente communément appelée voie visuelle principale ou en anglais « image forming visual pathways ». Le second, appelé système secondaire ou accessoire, n’apporte pas d’information visuelle consciente, il est dit « non image forming visual pathway ». Ce dernier apporte à notre cerveau une information sur l’environnement telle que la sensation jour/nuit. Ses fonctions sont sous-tendues par l’afflux d’informations rétiniennes non visuelles sur des structures de l’hypothalamus comme le noyau supra-chiasmatique. Les deux systèmes visuels ont un substratum anatomique complexe faisant intervenir de nombreuses structures anatomiques au sein des différents étages du cerveau cortical et sous-cortical comme les noyaux gris centraux dits « Basal Ganglias » (BG). Le système visuel secondaire intervient aussi comme une structure de contrôle des mouvements oculomoteurs tels que la poursuite ou les saccades nécessaires pour explorer notre environnement. Ainsi les saccades oculomotrices sont sous le contrôle modulateur des BG. De ce fait l’étude des saccades apparait comme un très bon modèle pour explorer le fonctionnement du système extrapyramidal au cours des maladies neuro-dégénératives. Les connaissances actuelles sur ce système de contrôle des saccades proviennent essentiellement des études sur le primate non humain et sur des observations cliniques chez l’homme au cours de pathologies dégénératives ou toxiques des BG. L’observation des structures anatomiques, en particulier du réseau de la substance blanche cérébrale qui supporte les connections axonales, n’est pas accessible à l’imagerie clinique de routine. Pour décrire et étudier ces réseaux de connections, la notion de connectomique a été introduite il y a un dizaine d’années. Dans ce travail, nous nous sommes donné l’objectif de décrire le connectome des saccades oculomotrices sur un plan structurel. Nous avons exploré les structures sous-corticales intervenant dans le contrôle des saccades comme les BG, le colliculus supérieur et le pulvinar. Pour ce faire, nous avons utilisé l’imagerie IRM structurelle en diffuseur de tension (DTI) chez deux groupes de patients présentant une maladie neuro-dégénérative : un groupe souffrant de maladie de Parkinson chez qui une atteinte des BG et une dysfonction des saccades sont reconnues, et un groupe de trembleurs essentiels reconnu pour ne pas présenter de dysfonction des saccades et chez qui les BG sont épargnés. Le résultat de ce travail a permis pour la première fois une description in vivo du connectome des saccades chez l’Homme. Il a de plus montré des différences dans la structure du connectome dans les deux groupes de patients. Une meilleure connaissance de ce connectome pourrait permettre de mieux comprendre certains troubles oculomoteurs et aussi de suivre l’évolution de certaines maladies neurodegeneratives. / Visual system is complex by its anatomy and its function. Neuro-anatomists have been interested in understanding the link between the visual pathways and the brain for centuries. Classical brain fixation and dissection methods were used to describe the visual pathways identifiable macroscopically. Non–image visual pathway, particularly the part involves in saccadic eye movements network in human is still not mastered. Our current knowledge in SCM is based on animal studies, anatomic dissection and brain histopathology examination of specimens from patients with clinical basal ganglia (BG) disorders. Saccadic eye movements (SCM) are under the control of the basal ganglia (BG) and SCM circuitry within the BG represents a good model for studying pathology in the extra-pyramidal system. The diagnosis of Parkinson’s disease (PD), which affects SEM and its distinction from non-dopaminergic, essential tremor (ET) where SEM are not impaired can be challenging and still relies on clinical observations. Diffusion tensor imaging and fiber tractography (DTI-FT), a new MRI technology, can be used to evaluate the presence and integrity of white matter tracts using directional diffusion patterns of water. The purpose of this study is to use DTI-FT to analyse SEM networks within BG and compare the SEM neural pathways or connectome of patients clinically diagnosed with PD and ET. To date, there are no studies, using DTI-FT for the extensive exploration of non-image visual pathways and SCM circuits, notably the deep brain connections. For this goal, we introduced the concept of SCM connectomes, derived from the general concept of connectome. Our study used structural MRI to identify nuclei and fascicles of the SCM connectome in PD and ET patients; imageries were acquired in routine clinical conditions fitted for DBS surgery. We found a reduction of the fiber number in two fascicles of the connectome in PDcompared to ET group.

Speed-accuracy tradeoffs, velocity profiles, and physiological tremor are fundamental characteristics of human movement. The principles underlying these phenomena have long attracted major interest and controversy. Each is well established experimentally but as yet they have no common theoretical basis. It is proposed that these three phenomena occur as the direct consequence of a movement response planning system that acts as an intermittent optimal controller operating at discrete intervals of ~100 ms. The BUMP model of response planning describes such a system. It forms the kernel of adaptive model theory which defines, in computational terms, a basic unit of motor production or BUMP. Each BUMP consists of three processes: (i) analysing sensory information, (ii) planning a desired optimal response, and (iii) executing that response. These processes operate in parallel across successive sequential BUMPs. The response planning process requires a discrete time interval in which to generate a minimum acceleration trajectory of variable duration, or horizon, to connect the actual response with the predicted future state of the target and compensate for executional error. BUMP model simulation studies show that intermittent adaptive optimal control employing two extremes of variable horizon predictive control reproduces almost exactly findings from several authoritative human experiments. On the one extreme, simulating spatially-constrained movements, a receding horizon strategy results in a logarithmic speed-accuracy tradeoff and accompanying asymmetrical velocity profiles. On the other extreme, simulating temporally-constrained movements, a fixed horizon strategy results in a linear speed-accuracy tradeoff and accompanying symmetrical velocity profiles. Furthermore, simulating ramp movements, a receding horizon strategy closely reproduces experimental observations of 10 Hz physiological tremor. A 100 ms planning interval yields waveforms and power spectra equivalent to those of joint-angle, angular velocity and electromyogram signals recorded for several speeds, directions, and skill levels of finger movement. While other models of response planning account for one or other set of experimentally observed features of speed-accuracy tradeoffs, velocity profiles, and physiological tremor, none accounts for all three. The BUMP model succeeds in explaining these disparate movement phenomena within a single framework, strengthening this approach as the foundation for a unified theory of motor control and planning.

The human jaw, like all other articulated body parts, exhibits small oscillatory movements during isometric holding tasks. These movements, known as physiological tremor, arise as a consequence of the interaction of various factors. One of these factors is reflex feedback from peripheral receptors. In the human jaw, receptors that innervate the periodontium are able to transduce minute changes in force. This thesis examines the contribution of these periodontal mechanoreceptors (PMRs) to the genesis of physiological tremor of the human jaw. By using frequency domain analysis of time series recorded during isometric biting tasks, the character of physiological jaw tremor can be revealed. Physiological jaw tremor was observed in force recorded from between the teeth as well as from electromyograms recorded from the principal muscles of mastication. These recordings have shown us that jaw physiological tremor consists of a frequency invariant component between 6 and 10Hz. This frequency remains unaltered under various load conditions where the mechanical resonance of the jaw would be expected to vary greatly (Chapter 2). Such findings indicate a ‘neurogenic’ origin for this tremor. A possible candidate for this neurogenic component of physiological tremor in the jaw is the reflex feedback arising from the PMRs. Using local anaesthetisation, it has been shown in this thesis, that by blocking outflow from the PMRs, the amplitude of neurogenic physiological jaw tremor can be reduced dramatically. This procedure caused a dramatic reduction in not only the mechanical recordings of tremor but also in the coupling between masseteric muscles bilaterally (Chapter 3) and between single motor units recorded from within a homonymous muscle (Chapter 4). The obvious mechanism by which periodontal mechanoreceptor anaesthetisation could reduce the amplitude of physiological tremor in the jaw would be by reducing the amplitude of the oscillatory input to the motoneurones driving the tremor. This interpretation remains controversial however as physiological tremor in the jaw can be observed at force levels above which the PMRs are supposedly saturated in their response. In light of this knowledge, the saturating characteristics of these receptors in terms of reflex output were examined. To do this, a novel stimulation paradigm was devised whereby the incisal teeth were mechanically stimulated with identical stimulus waveforms superimposed upon increasing tooth preloads. This necessitated the use of a frequency response method to quantify the reflexes. An optimal frequency for stimulation was identified and used to confirm that the hyperbolic saturating response of PMRs observed previously, translated to a similar phenomenon in masticatory reflexes (Chapter 5). These data reinforced the idea that physiological tremor in the jaw was not just a consequence of rhythmic reflex input from PMRs, as the dynamic reflex response uncoupled from the input as the receptor-mediated reflex response saturated. An alternative hypothesis was then developed that suggested the effect of PMR suppression in physiological tremor was via tonic rather than rhythmic effects on the masseteric motoneurone pool. By utilising a novel contraction strategy to manipulate the mean firing rate of the motor neuron pool at a given level of force production, data contained in Chapter 6 shows that population motor unit firing statistics influence the expression of physiological tremor, and such manipulations mimic, to an extent, the changes in firing statistics and tremor amplitude seen during anaesthetisation of the PMRs. This thesis therefore posits a mechanism whereby periodontal input influences the firing rate of motoneurones in such a way as to promote tremulous activity (Chapter 5). However, as this proposed mechanism did not explain the full extent of tremor suppression seen during PMR anaesthetisation it can therefore only be considered a contributing factor in a multifactor process. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1297555 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2007

Speed-accuracy tradeoffs, velocity profiles, and physiological tremor are fundamental characteristics of human movement. The principles underlying these phenomena have long attracted major interest and controversy. Each is well established experimentally but as yet they have no common theoretical basis. It is proposed that these three phenomena occur as the direct consequence of a movement response planning system that acts as an intermittent optimal controller operating at discrete intervals of ~100 ms. The BUMP model of response planning describes such a system. It forms the kernel of adaptive model theory which defines, in computational terms, a basic unit of motor production or BUMP. Each BUMP consists of three processes: (i) analysing sensory information, (ii) planning a desired optimal response, and (iii) executing that response. These processes operate in parallel across successive sequential BUMPs. The response planning process requires a discrete time interval in which to generate a minimum acceleration trajectory of variable duration, or horizon, to connect the actual response with the predicted future state of the target and compensate for executional error. BUMP model simulation studies show that intermittent adaptive optimal control employing two extremes of variable horizon predictive control reproduces almost exactly findings from several authoritative human experiments. On the one extreme, simulating spatially-constrained movements, a receding horizon strategy results in a logarithmic speed-accuracy tradeoff and accompanying asymmetrical velocity profiles. On the other extreme, simulating temporally-constrained movements, a fixed horizon strategy results in a linear speed-accuracy tradeoff and accompanying symmetrical velocity profiles. Furthermore, simulating ramp movements, a receding horizon strategy closely reproduces experimental observations of 10 Hz physiological tremor. A 100 ms planning interval yields waveforms and power spectra equivalent to those of joint-angle, angular velocity and electromyogram signals recorded for several speeds, directions, and skill levels of finger movement. While other models of response planning account for one or other set of experimentally observed features of speed-accuracy tradeoffs, velocity profiles, and physiological tremor, none accounts for all three. The BUMP model succeeds in explaining these disparate movement phenomena within a single framework, strengthening this approach as the foundation for a unified theory of motor control and planning.