BACKGROUND: Parkinson’s disease (PD) is a common debilitating disorder that largely effects the aging population. It is associated with a loss of dopamine-producing brain cells, which leads to abnormal brain activity and ultimately, a loss of locomotor control. Transcranial direct current stimulation (tDCS) is a technology that effectively modulates brain excitability by sending low electric current through the scalp. It has been demonstrated to improve working memory, intelligence, learning ability, as well as relieving symptoms of depression, Alzheimer’s and schizophrenia (Kekic, Boysen, Campbell, & Schmidt, 2015; Khedr et al., 2014; Manor et al., 2015). tDCS may thus serve as an effective therapeutic strategy for this vulnerable PD population. OBJECTIVE: The primary purpose of this study was to examine the acute effects of single sessions of tDCS targeting different brain networks on locomotor control metrics and other outcomes in patients with PD. DESIGN: A pilot, double-blinded, sham-controlled study. METHODS: A total of 15 older adults between the ages of 40-85 with a physician diagnosis of PD will be recruited. Participants are screened with questionnaires to determine eligibility. If eligible, participants will undergo a dual task assessment and a freezing of gait (FOG) provoking protocol prior to, as well as immediately after, a 20-minute session of tDCS. The acute effects of each stimulation session will be observed. There will be three different stimulation conditions that each target different areas of the brain: the motor cortex (M1), the motor cortex and the dorsolateral prefrontal cortex (DLPFC), and a sham (i.e., control) condition. Multiple aspects of locomotion (i.e., FOG, gait speed, stride time variability, percent of each walking stride spent with both feet on the ground) and cognition are assessed. RESULTS: This study began enrolling participants on March 3rd, 2016. To date, one participant has been enrolled and completed baseline testing as well as all three tDCS visits. This 42-year-old participant was diagnosed with PD two years ago and symptoms are mild. No side effects were observed during tDCS and the participant was unable to decipher between the M1 and the sham stimulation, but was able to tell the difference between sessions when receiving multi-focal stimulation. DISCUSSION: In this case study, tDCS was well tolerated by the patient and double-blinding procedures were effective. Thus, while tDCS did not induce significant improvements in gait or cognition in this relatively high functioning patient, the developed study protocol and tDCS intervention are highly feasible in the PD population.

Le risque de chute provoqué par le phénomène épisodique de ‘Freeze of Gait’ (FoG) est un symptôme commun de la maladie de Parkinson. Cette étude concerne la détection et le diagnostic des épisodes de FoG à l'aide d'un prototype multi-capteurs. La première contribution est l'introduction de nouveaux capteurs (télémètres et goniomètres) dans le dispositif de mesure pour la détection des épisodes de FoG. Nous montrons que l'information supplémentaire obtenue avec ces capteurs améliore les performances de la détection. La seconde contribution met œuvre un algorithme de détection basé sur des réseaux de neurones gaussiens. Les performance de cet algorithme sont discutées et comparées à l'état de l'art. La troisième contribution est développement d'une approche de modélisation probabiliste basée sur les réseaux bayésiens pour diagnostiquer le changement du comportement de marche des patients avant, pendant et après un épisode de FoG. La dernière contribution est l'utilisation de réseaux bayésiens arborescents pour construire un modèle global qui lie plusieurs symptômes de la maladie de Parkinson : les épisodes de FoG, la déformation de l'écriture et de la parole. Pour tester et valider cette étude, des données cliniques ont été obtenues pour des patients atteints de Parkinson. Les performances en détection, classification et diagnostic sont soigneusement étudiées et évaluées. / Freezing of Gait (FoG) is an episodic phenomenon that is a common symptom of Parkinson's disease (PD). This research is headed toward implementing a detection, diagnosis and correction system that prevents FoG episodes using a multi-sensor device. This particular study aims to detect/diagnose FoG using different machine learning approaches. In this study we validate the choice of integrating multiple sensors to detect FoG with better performance. Our first level of contribution is introducing new types of sensors for the detection of FoG (telemeter and goniometer). An advantage in our work is that due to the inconsistency of FoG events, the extracted features from all sensors are combined using the Principal Component Analysis technique. The second level of contribution is implementing a new detection algorithm in the field of FoG detection, which is the Gaussian Neural Network algorithm. The third level of contribution is developing a probabilistic modeling approach based on Bayesian Belief Networks that is able to diagnosis the behavioral walking change of patients before, during and after a freezing event. Our final level of contribution is utilizing tree-structured Bayesian Networks to build a global model that links and diagnoses multiple Parkinson's disease symptoms such as FoG, handwriting, and speech. To achieve our goals, clinical data are acquired from patients diagnosed with PD. The acquired data are subjected to effective time and frequency feature extraction then introduced to the different detection/diagnosis approaches. The used detection methods are able to detect 100% of the present appearances of FoG episodes. The classification performances of our approaches are studied thoroughly and the accuracy of all methodologies is considered carefully and evaluated

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Made available in DSpace on 2016-12-12T17:32:59Z (GMT). No. of bitstreams: 1 resumo MARIANA.pdf: 200440 bytes, checksum: c70e5f1ef3e842ad10423fc46fc308a9 (MD5) Previous issue date: 2015-07-30 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / As escalas Modified Parkinson Activity Scale (PASm) e a Lindop Parkinson s Disease Mobility Assessement (LPA) foram desenvolvidas para avaliar a mobilidade funcional em pacientes com Doença de Parkinson (DP) sendo diretamente aplicadas à prática fisioterapêutica. Os eventos de quedas prévios e o congelamento da marcha são considerados os principais fatores de risco para novas quedas na DP e apresentam influência direta sobre a mobilidade funcional. O objetivo do presente estudo foi realizar a tradução e adaptação transcultural das escalas PASm e LPA para a Língua Portuguesa-Brasil, e analisar algumas propriedades psicométricas, além de comparar o nível de mobilidade funcional com o congelamento da marcha e com os eventos de quedas vivenciados nos paciente com a DP. 32 indivíduos participaram do estudo. Considerando o escore total, as confiabilidades interavaliadores e teste-reteste apresentaram um coeficiente de correlação intra-classe que variou entre 0,97 e 0,98. Ambas as escalas apresentaram excelente consistência interna com coeficiente alfa de Cronbach variando entre 0,83 e 0,94. Foram obtidas excelentes correlações positivas entre as versões brasileiras da PASm e LPA e a PAS-Brasil, com valores entre _= 0,63 e 0,92. A validade concorrente entre as escalas e a UPDRS-parte III, estabeleceram uma moderada correlação negativa, (_=-0,54 e -0,65). A ANOVA one way mostrou que a LPA Brasil discrimina o indivíduo com DP entre todos os estágios segundo HY, e a PASm Brasil entre os estágios leve e grave, e moderado e grave. A MDC para as escalas variou entre 1 e 2 pontos. Houve efeito teto apenas para a LPA Brasil. Na comparação entre os grupos, o que congela obteve menor pontuação na escala PASm Brasil em relação ao que não congela (p=0,011) e a diferença significativa entre as médias das pontuações foram relativas às questões de mobilidade na cama (p=0,009). Além das tarefas do domínio de mobilidade da cama, o item 8 referente ao domínio da acinesia da marcha, apresentou diferença significativa entre as pontuações, p=0,033. O grupo que cai obteve menor pontuação na escala PASm Brasil em relação ao que não cai (p=0,018) e a diferença significativa entre as médias das pontuações dos grupos também foram relacionadas às questões de mobilidade na cama (p=0,015). Comparando o desempenho do grupo que cai e que não cai no TUG, o grupo que cai realizou o teste em maior tempo em relação ao que não cai (18,69s e 11,5s, respectivamente, p=0,006). Da mesma forma, o grupo que congela realizou o teste em maior tempo em relação ao que não congela (18,28s e 11,03s respectivamente, p=0,004). As versões brasileiras da PASm e LPA são instrumentos válidos e confiáveis para avaliar a mobilidade funcional no nível de atividade em pacientes com a DP, sendo diretamente aplicadas à prática clínica fisioterapêutica. O congelamento da marcha e os eventos de quedas vivenciados influenciam em alguns aspectos da mobilidade do paciente com DP, sobretudo na mobilidade na cama. Os achados deste estudo são relevantes uma vez que um dos principais objetivos da fisioterapia na DP é manter a mobilidade funcional e independência do paciente.

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Based on the belief that it is a locomotor control structure, the pedunculopontine tegmental nucleus (PPTg) has been considered a potential target for deep brain stimulation (DBS) for Parkinson's disease (PD) patients with symptoms refractory to medication and/or stimulation of established target sites. To date, a number of patients have been implanted with PPTg electrodes with mostly disappointing results. Exact target site in PPTg, possible mechanisms of PPTg-DBS and likely potential benefits need to be systematically explored before consideration of further clinical application. The research described here approaches these questions by (i) investigating the role of the PPTg in gait per se; (ii) developing a refined model of PD that mimics the underlying pathophysiology by including partial loss of the PPTg itself; (iii) adapting a wireless device to let rats move freely while receiving DBS; and (iv) investigating the effect of DBS at different sites in the PPTg on gait and posture in the traditional and refined model of PD. Underlining the concern that understanding the PPTg as a locomotor control structure is inadequate, the experiments showed that neither partial nor complete lesions of PPTg caused gait deficits. The refined model showed hardly any differences compared to the standard one, but the effect of DBS in each was very different, highlighting the need to take degeneration in the PPTg into consideration when investigating it as a DBS target. The differential results of anterior and posterior PPTg-DBS show the critical importance of intra-PPTg DBS location: Anterior PPTg electrodes caused severe freezing and worsened gait while some gait parameters improved with stimulation of posterior PPTg. The results suggest mechanisms of PPTg-DBS beyond the proposed activation of over-inhibited PPTg neurons, including aggravation of already dysfunctional inhibitory input by anterior PPTg-DBS and activation of ascending projections from posterior PPTg to the forebrain.

Les troubles de la marche et le freezing entraînent une invalidité sévère et ont un impact important sur la qualité de vie des patients souffrant de la maladie de Parkinson (MP). Ceci est d'autant plus vrai que ces troubles répondent mal aux traitements actuels, médicamenteux et chirurgicaux. Leurs mécanismes physiopathologiques sont largement incompris. Toutefois, leur résistance aux traitements courants suggère l'extension du processus lésionnel vers des structures non-dopaminergiques concourant au contrôle de la locomotion. L'implication du noyau pédonculopontin (PPN) a été évoquée. L'objectif de cette étude était de mieux comprendre les circuits neuronaux impliqués dans ces troubles, ainsi que leur modulation par les médicaments dopaminergiques et la stimulation du PPN. Les contraintes d'immobilité de la tête, liées à l'utilisation de la technique de tomographie par émission de positons (TEP), excluant la réalisation d'une épreuve effective de marche, la tâche a été effectuée en imagerie mentale. Les mêmes réseaux neuronaux sont en effet activés lors de la réalisation effective et la représentation mentale d'un mouvement, sous réserve que l'imagerie mentale motrice soit réalisée selon une perspective dite kinesthésique. Il était donc nécessaire, au préalable, de vérifier l'aptitude des patients à imager leur marche selon cette modalité. Nos données vont dans ce sens, et montrent qu'il est possible d'améliorer cette capacité à travers une préparation spécifique. De plus, l'utilisation d'un protocole comportemental d'imagerie mentale reposant sur la loi de Fitts a permis de familiariser les patients avec la tâche d'imagerie mentale en amont de la réalisation des examens TEP, mais aussi de vérifier leur engagement dans cette dernière durant les acquisitions cérébrales. Les résultats obtenus à l'issue de l'étude menée en imagerie cérébrale confirment la complexité de la physiopathologie des troubles locomoteurs, et suggèrent notamment différents niveaux d'atteinte, à l'étage cortical, sous cortical, et du tronc cérébral, selon la nature dopa-sensible ou dopa-résistante du trouble concerné. En particulier, la dérégulation frontale semble confirmée. De plus, un dysfonctionnement du tronc cérébral pourrait être lié à l'émergence des troubles de la marche et du freezing. Nous avons également constaté une implication pariétale, mais son rôle compensateur, ou pathologique, reste encore à définir. Le freezing dopa-sensible pourrait en partie refléter l'expression aggravée de la bradykinésie parkinsonienne, étant donné l'efficacité de la lévodopa sur ce symptôme. La stimulation de la région des PPN semble quant à elle restaurer une boucle cortico-cérebello-thalamo-corticale, facilitant le mouvement dans le cas des troubles dopa-résistants. Des investigations complémentaires, sur un échantillon plus large de patients, sont donc nécessaires pour approfondir ces résultats. Une meilleure compréhension de la physiopathologie de ces troubles est en effet indispensable pour le développement de nouvelles thérapeutiques dans le but d'améliorer la prise en charge des patients souffrant de ces troubles invalidants, et ainsi leurs répercussions en termes de santé publique. / Gait disorders, including freezing of gait are frequent and disabling symptoms that lead to severe decrease of the quality of life on patients from Parkinson's disease (PD). This is emphasized by the fact that those difficulties respond poorly to current medical and surgical treatments. The underlying pathophysiology remains largely unknown. However, the resistance to actual treatments suggests the extension of the degenerative process towards non-dopaminergic structures. Involvement of the pedonculopontine nucleus (PPN) has been proposed. The aim of the study was to better understand the neural networks involved in those troubles, as well as their modulation by dopaminergic drugs and PPN stimulation. The constraints related to stillness of the head during Positron Emission Tomography (PET) exclude, necessarily, the realization of an effective gait. This task has been accomplished using mental moor imagery. The same mural networks are, indeed, activated during the actual execution and the mental representation of movement, under the assumption that motor mental imaging is undertaken from a kinesthetic perspective. Thus, it was necessary, preliminarily to this study, to control the ability of patients to imagine themselves walking from a kinesthetic point of view. Our data validate this condition. Moreover, they show that it is possible to improve this ability through a specific training. What is more, the use of a behavioral protocol, based on Fitt's law, helped the patients to familiarize themselves with this approach, before PET acquisitions, but also to control their correct performance during PET scan. The results, which have been obtained in cerebral imaging confirm the complexity of the underlying mechanisms of gait disorders, and suggest notably different levels of deregulation, on a cortical, sub-cortical and brainstem. In particular, frontal deregulation appears to be confirmed. Moreover, a deregulation of the brainstem could be more particularly involved in gait disorders apparition. We have also evidenced parietal implication, but its exact compensatory or pathologic role remains to be determined. Levodopa-responsive freezing seems to be a consequence of worsened parkinsonian bradykinesia. PPN stimulation seems able to restore a functional cortico-cerebello-cortical loop, facilitating movement. Complementarily studies, on a larger selection of patients, are thus necessary to complete those results. A better understanding of pathophysiology is, as a matter of fact, necessary for the development of new therapeutics in order to improve the therapy of patients from those very invalidating troubles, and thus, to reduce their impact on public health.

Les patients atteints de maladie de Parkinson présentent des troubles de la marche, parfois paroxystiques, pouvant être aggravés ou améliorés par les stimuli environnementaux. L'attention portée, soit aux stimuli extérieurs, soit à la marche, pourrait ainsi moduler la locomotion.L’objectif principal était donc de mieux caractériser la manière dont les stimuli environnementaux modulent par le biais de réseaux attentionnels la locomotion. Ceci a été étudié chez les sujets sains puis chez les patients parkinsoniens, avec ou sans enrayage cinétique.Nous avons d'abord défini précisément les déficits attentionnels des patients, avec ou sans troubles de la marche. Ils présentaient respectivement des difficultés en flexibilité mentale et plus particulièrement en attention divisée.Nous avons ensuite exploré l'interaction attention-locomotion grâce à l'étude de la préparation motrice. Ainsi, nous avons pu démontrer que les ajustements posturaux anticipés étaient un marqueur sensible de l’attention. Chez les patients, ils pouvaient témoigner d’une altération de l'interaction attention-programmation motrice.L'étude des régions cérébrales activées lors de la locomotion visuo-guidée chez ces patients a permis de confirmer l'implication de structures corticales attentionnelles. Un déséquilibre d’activation au sein du réseau pariéto-prémoteur (nécessaire à la modulation de l'action motrice en fonction des stimuli externes) était présent.Enfin, nous avons essayé de modifier l'excitabilité du cortex prémoteur via des techniques de stimulation magnétique transcrânienne répétitive afin de moduler la locomotion visuo-guidée. / Patients with Parkinson 's disease present gait impairments, sometimes sudden and unexpected, either improved or deteriorated with environmental stimuli. Attention focalization, either on external stimuli or on gait, could then modulate locomotion.The main objective was to better characterize how environmental stimuli would modulate locomotion, via attentional networks, in healthy subjects and in parkinsonian patients, with or without freezing of gait.At first, we precisely defined the attentional deficits in patients, with or without gait impairment. They showed altered performance respectively in mental flexibility and in divided attention.Then, we explored the attention-locomotion interaction by studying motor preparation. So, we highlighted that anticipatory postural adjustments were a sensitive marker of attention. In patients, they evidenced an alteration of the attention-motor program interaction.Studying the brain activation during the visuo-driven locomotion in these patients confirmed the involvement of cortical attentional regions. We observed an imbalance inside the parieto-premotor network (useful to modulate motor action according external stimuli)Finally, we tried to change the excitability of the premotor cortex with transcranial magnetic stimulation to modulate visuo-driven locomotion.

Hypokinetická dysartrie (HD) je častým symptomem vyskytujícím se až u 90% pacientů trpících idiopatickou Parkinsonovou nemocí (PN), která výrazně přispívá k nepřirozenosti a nesrozumitelnosti řeči těchto pacientů. Hlavním cílem této disertační práce je prozkoumat možnosti použití kvantitativní paraklinické analýzy HD, s použitím parametrizace řeči, statistického zpracování a strojového učení, za účelem diagnózy a objektivního hodnocení PN. Tato práce dokazuje, že počítačová akustická analýza je schopná dostatečně popsat HD, speciálně tzv. dysprozodii, která se projevuje nedokonalou intonací a nepřirozeným tempem řeči. Navíc také dokazuje, že použití klinicky interpretovatelných akustických parametrů kvantifikujících různé aspekty HD, jako jsou fonace, artikulace a prozodie, může být použito k objektivnímu posouzení závažnosti motorických a nemotorických symptomů vyskytujících se u pacientů s PN. Dále tato práce prezentuje výzkum společných patofyziologických mechanizmů stojících za HD a zárazy v chůzi při PN. Nakonec tato práce dokazuje, že akustická analýza HD může být použita pro odhad progrese zárazů v chůzi v horizontu dvou let.