Schizophrenia is a mental illness with early adult onset. Prophylactic treatments would be clinically important and therefore we investigated the effect of two interventions: influenza vaccination of pregnant mothers and valproate treatment during late adolescence. Maternal immune response during pregnancy is thought to adversely affect brain development. We sought to assess whether immune activation by influenza vaccine could itself cause behavioural abnormalities in a mouse model. Our data suggest that further work is needed to make firm conclusions about the behavioural effects of the influenza vaccine. The second part of this thesis describes an analysis of valproate treatment on cortical neuron morphology in Disc1 L100P mice, a model for schizophrenia. Valproate was previously shown to prevent the onset of abnormal behaviours in Disc1 L100P mice. Contrary to expectations, valproate decreased apical spine density and the number of dendritic processes rather than reversing the dendritic deficits seen in Disc1 L100P mice.

La perception de mouvements est associée à une augmentation de l’excitabilité du cortex moteur humain. Ce système appelé « miroir » sous-tendrait notre habileté à comprendre les gestes posés par une tierce personne puisqu’il est impliqué dans la reconnaissance, la compréhension et l’imitation de ces gestes. Dans cette étude, nous examinons de quelle façon ce système miroir s’implique et se latéralise dans la perception du chant et de la parole. Une stimulation magnétique transcrânienne (TMS) à impulsion unique a été appliquée sur la représentation de la bouche du cortex moteur de 11 participants. La réponse motrice engendrée a été mesurée sous la forme de potentiels évoqués moteurs (PÉMs), enregistrés à partir du muscle de la bouche. Ceux-ci ont été comparés lors de la perception de chant et de parole, dans chaque hémisphère cérébral. Afin d’examiner l’activation de ce système moteur dans le temps, les impulsions de la TMS ont été envoyées aléatoirement à l’intérieur de 7 fenêtres temporelles (500-3500 ms). Les stimuli pour la tâche de perception du chant correspondaient à des vidéos de 4 secondes dans lesquelles une chanteuse produisait un intervalle ascendant de deux notes que les participants devaient juger comme correspondant ou non à un intervalle écrit. Pour la tâche de perception de la parole, les participants regardaient des vidéos de 4 secondes montrant une personne expliquant un proverbe et devaient juger si cette explication correspondait bien à un proverbe écrit. Les résultats de cette étude montrent que les amplitudes des PÉMs recueillis dans la tâche de perception de chant étaient plus grandes après stimulation de l’hémisphère droit que de l’hémisphère gauche, surtout lorsque l’impulsion était envoyée entre 1000 et 1500 ms. Aucun effet significatif n’est ressorti de la condition de perception de la parole. Ces résultats suggèrent que le système miroir de l’hémisphère droit s’active davantage après une présentation motrice audio-visuelle, en comparaison de l’hémisphère gauche. / The perception of movements is associated with increased activity in the human motor cortex. This system underlies our ability to understand one’s actions, as it is implicated in the recognition, understanding and imitation of actions. In this study, we investigated the involvement and lateralization of this “mirror neuron” system (MNS) in the perception of singing and speech. Transcranial magnetic stimulation (TMS) was applied over the mouth representation of the motor cortex in 11 participants. The generated motor response was measured in the form of motor evoked potentials (MEPs), recorded from the mouth muscle. The MEPs were compared for the singing and speech conditions in each cerebral hemisphere. Furthermore, to investigate the time course of the MNS activation, TMS pulses were randomly emitted in 7 time windows (ranging from 500 to 3500 milliseconds after stimulus onset). The stimuli for the singing condition consisted in 4-second videos of singers producing a 2-note ascending interval. Participants had to judge whether the sung interval matched a written interval, previously presented on the screen. For the speech condition, 4-second videos of a person explaining a proverb were shown. Participants had to decide whether this explanation matched a written proverb previously displayed on the screen. Results show that the MEP amplitudes were higher after stimulation of the right hemisphere in the singing condition. More specifically, sending TMS pulses between 1000 and 1500 milliseconds over the right hemisphere yielded higher MEPs as compared to the left hemisphere. No effect was found in the speech condition. These results suggest that the right MNS is more activated after an audiovisual motor presentation compared to the left hemisphere.

Su amžiumi susiję struktūriniai simpatinės nervų sistemos pokyčiai sukelia įvairių organų funkcijos sutrikimus. Simpatinio kamieno viršutiniai kakliniai mazgai, pagrindiniai galvos smegenų kraujagyslių simpatinės inervacijos šaltiniai, yra svarbūs galvos smegenų kraujotakos autonominės reguliacijos centrai. Tačiau žmogaus simpatinių mazgų morfofunkciniai tyrimai yra pavieniai. Todėl šio darbo tikslas buvo ištirti trijų amžiaus grupių žmonių ir mirusiųjų dėl išeminio galvos smegenų infarkto simpatinio kamieno viršutinio kaklinio mazgo morfologinius bei neurocheminius ypatumus, ir nustatyti jų sąsajas su amžiumi ir išeminiu galvos smegenų infarktu. Tyrimo rezultatai rodo, kad amžiaus eigoje vystosi žmogaus simpatinio kamieno viršutinio kaklinio mazgo neuronų morfologinių parametrų, neurofilamentų baltymo, nervų augimo faktoriaus receptorių p75 imunoreaktyvumo pokyčiai. Skirtingose amžiaus grupėse aptinkami neuronų ir satelitinių ląstelių apoptoz����s požymiai. Pagyvenusio amžiaus žmonių, mirusių dėl išeminio galvos smegenų infarkto, simpatiniuose mazguose vystosi neuropatologinės alteracijos požymiai: padidėja neuronų afinitetas baziniams dažams, atsiranda neuronų su degeneraciniais ir hipertrofijos požymiais židiniai, satelitinių ląstelių proliferacija, limfocitų židininė infiltracija, sumažėja neuronų kūno, branduolio, citoplazmos plotai, aptinkamas didesnis neurofilamentams ir nervų augimo faktoriaus receptoriams p75 imunoreaktyvių neuronų skaičius, didesnis apoptozinis... [toliau žr. visą tekstą] / Age-related structural changes of the sympathetic nervous system cause the disturbance of the involuntary functions of various organs. The superior cervical ganglia are the main source of sympathetic innervation of the cerebral arteries and important center of autonomic regulation of the cerebral circulation. However, only single morphofunctional studies of the human sympathetic ganglia are performed. Therefore, the aim of the study was to investigate morphological and neurochemical peculiarities of the human superior cervical ganglion in three age groups and in the subjects dead of ischemic cerebral infarction and establish their relation to age and ischemic cerebral infarction. The results of the present study show that changes of neurons morphologic parameters and immunoreactivity to neurofilament and nerve growth factor receptor p75 in the human superior cervical ganglion are developed in the course of aging. Morphological features of apoptosis in the sympathetic neurons and satellite cells in different age groups are detected. The signs of neuropathological alteration of the sympathetic ganglion of subjects with ischemic cerebral infarction were the following: increased tinctorial affinity of neurons, foci of neurons with features of neuron death and hypertrophy, proliferation of satellite cells, focal lymphocyte infiltration, decrease of neuron body, nucleus, cytoplasm area, increase of neurofilament and nerve growth factor receptor p75 immunoreactive neurons... [to full text]

Schizophrenia is a mental illness with early adult onset. Prophylactic treatments would be clinically important and therefore we investigated the effect of two interventions: influenza vaccination of pregnant mothers and valproate treatment during late adolescence. Maternal immune response during pregnancy is thought to adversely affect brain development. We sought to assess whether immune activation by influenza vaccine could itself cause behavioural abnormalities in a mouse model. Our data suggest that further work is needed to make firm conclusions about the behavioural effects of the influenza vaccine. The second part of this thesis describes an analysis of valproate treatment on cortical neuron morphology in Disc1 L100P mice, a model for schizophrenia. Valproate was previously shown to prevent the onset of abnormal behaviours in Disc1 L100P mice. Contrary to expectations, valproate decreased apical spine density and the number of dendritic processes rather than reversing the dendritic deficits seen in Disc1 L100P mice.

Disertacijoje nagrinėjami nestacionarių matematinių modelių nestandartinėse srityse skaitiniai sprendimo algoritmai. Uždavinio formulavimo sritis yra šakotosios struktūros (ang. branching structures), kurių išsišakojimo taškuose apibrėžiami tvermės dėsniai. Tvermės dėsnių skaitinė analizė ir nestandartinių kraštinių sąlygų analizė skiria nagrinėjamus uždavinius nuo klasikinių aprašytų literatūroje matematinės fizikos uždavinių. Disertacijoje suformuluoti uždaviniai apima skaitinių algoritmų šakotose struktūrose su skirtingais srautų tvermės dėsniais stabilumo ir konvergavimo tyrimą, lygiagrečiųjų algoritmų sudarymą ir taikymą, skaitinių schemų uždaviniams su nelokaliomis integralinėmis sąlygomis tyrimą. Disertacijoje sprendžiami taikomieji neurono sužadinimo ir impulso relaksacijos lazerio apšviestame puslaidininkyje uždaviniai, netiesinio modelio identifikavimo uždavinys. Disertaciją sudaro įvadas, penki skyriai, rezultatų apibendrinimas, literatūros šaltinių sąrašas ir autorės publikacijų disertacijos tema sąrašas. Įvadiniame skyriuje formuluojama problema, aprašytas tyrimų objektas, darbo aktualumas, formuluojami darbo tikslai ir uždaviniai, aprašoma tyrimų metodika, darbo mokslinis naujumas, darbo rezultatų praktinė reikšmė, pateikti ginamieji teiginiai ir disertacijos struktūra. Pabaigoje pristatomi pranešimai konferencijose disertacijos tema. Pirmajame skyriuje pateikta matematinių modelių nestandartinėse srityse arba su nestandartinėmis sąlygomis apžvalga. Antrajame... [toliau žr. visą tekstą] / The numerical algorithms for non-stationary mathematical models in non-standard domains are investigated in the dissertation. The problem definition domain is represented by branching structures with conjugation equations considered at the branching points. The numerical analysis of the conjugation equations and non-classical boundary conditions distinguish considered problems among the classical problems of mathematical physics presented in the literature. The scope of the dissertation covers the investigation of stability and convergence of the numerical algorithms on branching structures with different conjugation equations, the construction and implementation of parallel algorithms, the investigation of the numerical schemes for the problems with nonlocal integral conditions. The modeling of the excitation of neuron and photo-excited carrier decay in a semiconductor, also the problem of the identification of nonlinear model are considered in the dissertation. The dissertation consists of an introduction, five chapters, main conclusions, bibliography and the list of the author's publications on the topic of dissertation. Introductory chapter covers the problem formulation and the object of research, the topicality of the thesis, the aims and objectives of the dissertation, the methodology of research, scientific novelty and the practical value of the achieved results. The defended thesis and structure of the dissertation are given in this chapter. The first chapter... [to full text]

The numerical algorithms for non-stationary mathematical models in non-standard domains are investigated in the dissertation. The problem definition domain is represented by branching structures with conjugation equations considered at the branching points. The numerical analysis of the conjugation equations and non-classical boundary conditions distinguish considered problems among the classical problems of mathematical physics presented in the literature. The scope of the dissertation covers the investigation of stability and convergence of the numerical algorithms on branching structures with different conjugation equations, the construction and implementation of parallel algorithms, the investigation of the numerical schemes for the problems with nonlocal integral conditions. The modeling of the excitation of neuron and photoexcited carrier decay in a semiconductor, also the problem of the identification of nonlinear model are considered in the dissertation. / Disertacijoje nagrinėjami nestacionarių matematinių modelių nestandartinėse srityse skaitiniai sprendimo algoritmai. Uždavinio formulavimo sritis yra šakotosios strukturos (ang. branching structures), kurių išsišakojimo taškuose apibrežiami tvermės dėsniai. Tvermės dėsnių skaitinė analizė ir nestandartinių kraštinių sąlygų analizė skiria nagrinėjamus uždavinius nuo klasikinių aprašytų literatūroje matematinės fizikos uždaviniu. Disertacijoje suformuluoti uždaviniai apima skaitinių algoritmų šakotose struktūrose su skirtingais srautų tvermės dėsniais stabilumo ir konvergavimo tyrimą, lygiagrečiųjų algoritmų sudarymą ir taikymą, skaitinių schemų uždaviniams su nelokaliomis integralinėmis sąlygomis tyrimą. Disertacijoje sprendžiami taikomieji neurono sužadinimo ir impulso relaksacijos lazerio apšviestame puslaidininkyje uždaviniai, netiesinio modelio identifikavimo uždavinys.

Spasticity is highly prevalent in neurological conditions involving upper motor neuron lesions (UMNL). Lower limb spasticity is known to impair gait and limit participation in physical activity. Multimodal interventions including botulinum toxin A, orthoses, and physiotherapy have shown longer lasting improvements compared to unimodal interventions. Studies to date, however, have not examined the long term efficacy of this multimodal intervention nor have they examined the impact across a breadth of domains necessary to comprehensively and fully understand its impact. The aim of this study was to investigate the efficacy of a multimodal intervention to treat lower limb spasticity in adults using a longitudinal mixed-methods approach, including a comprehensive set of outcome measures spanning the domains of the International Classification of Functioning, Disability and Health (ICF) model. Seven-teen participants with chronic UMNL were included in the analysis as per inclusion criteria and showed improvements at 6 and 12 months, compared to baseline, within all domains of the ICF model. / Graduate / 0571 / 0382 / 0384 / jazkim@uvic.ca

La panne de moteur est une situation critique pour la sécurité du vol. L'objectif de cette thèse est d'améliorer la gestion de la trajectoire avion d'urgence dans le cas d'une panne totale de moteur en un certain point de vol alors que l'avion a déjà pris une certaine vitesse et une certaine altitude après le décollage. Dans cette étude, on considère que la trajectoire de vol plané le long d'un plan vertical peut conduire directement à un lieu atterrissage sûr. Les performances d'un avion de transport sont d'abord analysées, et les lieus atteignables sont établis à partir d'une situation donnée initiale. Une fois une zone de sécurité accessible existe le problème qui est abordée ici est de développer un système de guidage qui permet à l'avion d'effectuer une trajectoire faisable vers la zone d'atterrissage. La programmation dynamique inverse est utilisée pour construire en arrière des ensembles de trajectoires faisables vers conditions finales compatibles avec panne de moteur. Afin d'obtenir un dispositif en ligne pour générer des directives efficaces pour le pilote automatique ou le pilote humain (par un directeur de vol), un réseau de neurones est construit à partir de la base de données générée. Ensuite, les résultats de simulation sont analysés pour validation, et d'autres améliorations de l'approche proposée sont prises en considération.

Spasticity is highly prevalent in neurological conditions involving upper motor neuron lesions (UMNL). Lower limb spasticity is known to impair gait and limit participation in physical activity. Multimodal interventions including botulinum toxin A, orthoses, and physiotherapy have shown longer lasting improvements compared to unimodal interventions. Studies to date, however, have not examined the long term efficacy of this multimodal intervention nor have they examined the impact across a breadth of domains necessary to comprehensively and fully understand its impact. The aim of this study was to investigate the efficacy of a multimodal intervention to treat lower limb spasticity in adults using a longitudinal mixed-methods approach, including a comprehensive set of outcome measures spanning the domains of the International Classification of Functioning, Disability and Health (ICF) model. Seven-teen participants with chronic UMNL were included in the analysis as per inclusion criteria and showed improvements at 6 and 12 months, compared to baseline, within all domains of the ICF model. / Graduate / 2015-04-24 / 0571 / 0382 / 0384 / jazkim@uvic.ca

To identify the risk factors being associated with aetiology of amyotrophic lateral sclerosis (ALS), a series of systematic reviews based on existing observational epidemiological studies identified through searching of bibliographic databases were conducted. Associations between ALS and a number of genetic and environmental risk factors were examined using meta-analysis. Specifically we found that previous exposure to lead, pesticides, solvents, experience of trauma and electric shock were associated with relative increased risks of developing ALS of 86% [odds ratio (OR) =1.86, 95% CI: 1.39-2.48], 57% (OR=1.57,95% CI: 1.19-2.08), 47% (OR=1.47, 95%CI: 1.13-1.80), 64% (OR=1.64; 95%CI: 1.36-1.98), and 2.27% (OR=3.27, 95%CI:1.87-5.73) respectively, compared to their corresponding controls. The presence of intermediate CAG repeat expansion in the ATXN2 gene was associated with a 4.4 -fold increase in the risk of ALS (OR=4.44, 95%CI: 2.91-6.76). However, the attributable risk associated with each identified risk factor was estimated to be less than 5% of all ALS cases. These results confirm that ALS is a rare multifactorial degenerative condition of motor-neurons.