Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) which can be defined as chronic, relapsing visceral pain with bloating associated with change in bowel habit. It affects up to 10-15% of the adult population in the UK and is more common in females. The cost of IBS in terms of health care utilisation is substantial, exceeding £45.6 million per year in the UK alone, yet its pathophysiology is incompletely understood. Visceral pain is the main and most difficult symptom to manage in IBS and many IBS female sufferers compare it to labour pain in its severity. Modulating visceral pain in healthy volunteers and IBS patients is therefore an important research area. Non-invasive magnetic stimulation may play a crucial role in this respect. Aim:The aim of this study is to ascertain whether non-invasive repetitive magnetic stimulation applied to the motor cortex and/or lumbosacrum can modulate gastrointestinal pain originating from the anorectum. Methods:Participants: 16 healthy volunteers and 10 IBS patients aged 18 and above were included in the study.Questionnaires: Healthy volunteers and IBS patients were asked to complete anxiety and depression questionnaire and IBS patients were requested to fill in an IBS severity questionnaire.Motor measurements in healthy subjects: Single-pulse lumbosacral magnetic stimulation (LSMS) was applied to the lumbosacral area for the anal sphincter where the largest motor evoked potential (MEP) amplitude response was detected. Single-pulse transcranial magnetic stimulation (TMS) was then performed at the pre-determined resting motor thresholds (RMT) for the anal sphincter and the hand.Sensory measurements in healthy subjects and IBS patients: Electrical stimulation was used to assess the changes in sensory and pain thresholds in the anorectal area. The subjects were asked to score the pain intensity using five-point categorical rating scales. In addition they were asked to describe the pain experienced using a shortened form of the McGill Pain Questionnaire. Intervention: Healthy volunteers received 6 paradigms of magnetic stimulation in a randomised order i.e. 3 repetitive LSMSs (1 Hz, 10 Hz and sham) and 3 repetitive TMSs (1 Hz, 10 Hz and sham) to investigate their modulatory effects on visceral sensitivity and to determine which of these interventions is most effective. The most effective active interventions (1 Hz rLSMS and 10 Hz rTMS) together with one sham were then trialled in a randomised fashion on IBS patients.Post intervention: Motor excitabilities were repeated at 30 min after each intervention. The assessment of sensory and pain thresholds at anal sphincter and rectum were done immediately, 30 and 60 min after each intervention. Results:Application of 1 Hz rLSMS led to alterations of anal sphincter motor excitabilities and resulted in a significant increase in the amplitude of lumbosacal-anal motor evoked potentials (MEPs) in healthy volunteers recorded at 30 min post intervention. In healthy volunteers, 1 Hz rLSMS and 10 Hz rTMS caused a significant increase in the rectal pain thresholds experienced immediately, 30 and 60 min after each intervention. 10 Hz rLSMS and 1 Hz rTMS only led to a significant rise in rectal pain thresholds immediately after their application. Furthermore, there was a significant increase in the rectal pain thresholds immediately, 30 and 60 min following 1 Hz rLSMS and 10 Hz rTMS in IBS patients. Conclusion:The application of magnetic stimulation to the cortical and lumbosacral areas to modulate visceral pain is a new concept, which reduced rectal sensitivity to painful stimuli and offers a much needed new approach in the management of abdominal pain in patients with IBS.

Les champs électromagnétiques sont couramment utilisés pour stimuler de manière non-invasive le cerveau humain soit à des fins thérapeutiques ou dans un contexte de recherche. Les effets de la stimulation magnétique varient en fonction de la fréquence et de l'intensité du champ magnétique. Les mécanismes mis en jeu restent inconnus, d'autant plus lors de stimulations à faible intensité. Dans cette thèse, nous avons évalué les effets de stimulations magnétiques répétées à différentes fréquences appliqués à faible intensité (10-13 mT ; Low Intensity Repetitive Magnetic Stimulation : LI-rMS) in vitro, sur des cultures corticales primaires et sur des modèles de réparation neuronale. De plus, nous décrivons une méthodologie pour la construction d'un dispositif instrumental fait sur mesure pour stimuler des cultures cellulaires.Les résultats montrent des effets dépendant de la fréquence sur la libération du calcium des stocks intracellulaires, sur la mort cellulaire, sur la croissance des neurites, sur la réparation neuronale, sur l'activation des neurones et sur l'expression de gènes impliqués. En conclusion, nous avons montré pour la première fois un nouveau mécanisme d'activation cellulaire par les champs magnétiques à faible intensité. Cette activation se fait en l'absence d'induction de potentiels d'action. Les résultats soulignent l'importance biologique de la LI-rMS par elle-même mais aussi en association avec les effets de la rTMS à haute intensité. Une meilleure compréhension des effets fondamentaux de la LI-rMS sur les tissus biologiques est nécessaire afin de mettre au point des applications thérapeutiques efficaces pour le traitement des conditions neurologiques. / Electromagnetic fields are widely used to non-invasively stimulate the human brain in clinical treatment and research. This thesis investigates the effects of different low intensity (mT) repetitive magnetic stimulation (LI-rMS) parameters on single neurons and neural networks and describes key aspects of custom tailored LI-rMS delivery in vitro. Our results show stimulation specific effects of LI-rMS on cell survival, neuronal morphology, neural circuit repair and gene expression. We show novel mechanisms underlying cellular responses to stimulation below neuronal firing threshold, extending our understanding of the fundamental effects of LI-rMS on biological tissue which is essential to better tailor therapeutic applications.

Les Troubles Obsessionnels Compulsifs (TOC) sont composés de compulsions, qui sont des comportements répétés, et d'obsessions, qui sont des pensées intrusives. Leurs impacts sur le fonctionnement socio-professionnel handicapent et isolent considérablement les patients. Les traitements efficaces pour ces patients sont médicamenteux ou les thérapies cognitives et comportementales. Néanmoins, un nombre élevé de patients ne voient pas leurs symptômes diminuer suffisamment avec l'un ou l'autre des traitements ou en les combinant. Il est donc nécessaire de développer des traitements intermédiaires afin d'améliorer la palette de traitements des TOC. Une alternative thérapeutique utilisée en psychiatrie pour la dépression est la Stimulation Magnétique Transcrânienne répétée (TMS). Néanmoins, son efficacité reste difficile à démontrer dans le TOC, dû à une multitude de facteurs à prendre en compte, et peut nécessiter d'étudier le fonctionnement de la rTMS sur une population de sujets sains. Lors de notre première étude, nous avons évalué l'impact d'un protocole de rTMS sur les fonctions cognitives de sujets sains. Nous avons donc pu observer, indépendamment de la pathologie, l'effet de deux semaines de TMS sur les performances cognitives et sur l'activité cérébrale. Malgré une absence d'effet comportemental, une modification du réseau cortico-sous-cortical lié à une tâche de mémoire de travail a pu être montrée. Ces résultats orientent les recherches futures à modifier l'approche méthodologique, améliorer l'approche clinique des TOC, et changer l'approche neurophysiologique de la TMS dans le but de proposer un traitement complémentaire pour améliorer l'état clinique des patients. / Obsessive Compulsive Disorder (OCD) is a mental illness defined by the presence of compulsions which are repetitive behaviors and obsessions which are intrusive thoughts. OCD may have a dramatic impact on the social and professional lifes of patients. The treatments for OCD are medication and cognitive-behavioral therapy. Nevertheless, symptoms remain in 25 to 40% of patients. Repeated Transcranial Magnetic Stimulation (rTMS) represent a novel therapeutic option for OCD patients however its effectiveness has been difficult to prove partly due to a multitude of factors involving the rTMS technique itself. The first study evaluated the impact of a two-week rTMS protocol on cognitive functions in healthy subjects using fMRI during a working-memory task. In the absence of behavioral modification, we observed that compared to sham, rTMS induced changes at multiple nodes of the cerebral network activated by the task beyond the stimulation site. This result represents an encouraging perspective for rTMS intervention on pathological brain network in OCD because hyperactive regions in this disorder (orbitofrontal cortex and anterior cingulate cortex) are too deep to be directly stimulated by rTMS. Our second study targeted the supplementary motor area (SMA), which had been suggested as candidate target region lying near the anterior cingulate cortex. We used for four week rTMS in a group of OCD patients while pre- and post-treatment fMRI was acquired during performance of a cognitive inhibition task. Stimulation of the SMA did not result in significant clinical improvement. These results shall guide future research to address the methodological challenges and the neurophysiological mechanisms of rTMS to improve its clinical efficacy for OCD.

No description available.

Hemispatial neglect, is a major cause of post-stroke disability and poor functional recovery. Hence, identifying sensitive methods to assess and rehabilitate neglect is important. Chapters 3 and 4 focused on development of novel assessment techniques for representational neglect. The 'Shopping Mall' and 'Clock Cueing' tasks improved upon previous tests and were useful in identifying dissociations in representational neglect based on type of stimuli (topological, non-topological) and time of assessment (pre-stroke, post-stroke) in chronic stroke patients. Chapters 5 and 6 investigated the efficacy of offline inhibitory repetitive Transcranial Magnetic Stimulation (rTMS) in producing short (<1 month) and long term (>6 months) changes in visual neglect behaviour. Overall, the findings from these chapters were limited due to lack of sufficient power. After controlling for the effect of baseline performance, the Intervention group's Activities of Daily Living scores significantly improved in the short-term post rTMS, as compared to the Control group. The fMRI task attempted to recruit attention-based top down modulation of sensory activity. It revealed relative hypoactivation of the right occipital lobe in the four left neglect patients tested, both pre and post rTMS, when compared to elderly controls. Chapter 7 explored cognitive predictors of spatial and object neglect in the sub-acute stage after controlling for demographic and stroke related factors, using multivariate blocked logistic regressions. Cognitive performance indicative of spatial attention and selective attention to local features predicted both spatial and object neglect. In addition, coding of spatial relations between features also predicted spatial neglect. Suggestions for combining neglect rehabilitation techniques to target these cognitive processes are discussed. Overall, this thesis provides novel methods to improve representational neglect assessment and highlights the importance of ancillary cognitive domains in contributing to both representational and visual neglect. The rTMS research provides study design-related insights to incorporate in future studies with larger patient samples.

The management of equipment based on Reliability-Centered Maintenance (RCM) has been widely applied with great success in several industries such as military, commodity production, civil airliners, nuclear power plant and the petroleum industry since the reprint of RCM-II written by John Moubray in 1997.The application of RCM not only increases the reliability of the equipment and the assets of a company but also promotes the overall equipment effectiveness (OEE), which includes the excellent ok yield to order and the better productivity of the equipment. As a methodology, RCM differs from the traditional equipment maintenance in the aspect of emphasis of maintaining the ¡§function¡¨ of the equipment instead of the equipment itself. Therefore, the need of equipment maintenance results from the speed and the severity of function loss, which determines the strategy and interval of equipment maintenance. This is the major difference between RCM and time based maintenance (TBM). This article discusses the critical success factors that drive the application of RCM in steel plant. The result reveals that the application of RCM could promote the reliability of equipment, cut the cost of maintenance and increase compatibility of the steel plant. In order to facilitates the implementation of RCM in the steel mill, the basic skills of the management includes the construction of vision¡Bconsensus¡Bthe set up of regulation and the cultivation of innovating culture. so as to build an effective managing teamwork features in strong execution. As for the equipment management both the standardization and the strict deviation of equipment function(6£m) are vital to sustain the excellent equipment reliability. The Integration of Maintenance Management System(IMMS) consists of three components, CMMS(Computerized Maintenance Management System) and RTMS(Real Time Monitoring System) link by RCM. RCM acts as a bridge for the information flow of maintenance management in the IMMS and promotes the effectiveness of maintenance management.

La commande de la ventilation chez l'humain est capable d'adaptation persistante qui repose sur des mécanismes de type LTP. Différentes techniques permettant l'induction de plasticité sont couramment utilisées mais leur application au contrôle ventilatoire n'a fait l'objet que de très peu de travaux.L'objectif de cette thèse est (1) examiner la possibilité d'induire des mécanismes de type LTP par la rTMS et la tsDCS en deux sites de la commande ventilatoire destinée au diaphragme, l'AMS et les métamères C3-C5 ; (2) évaluer les conséquences sur le profil ventilatoire en ventilation de repos et lorsque la ventilation est artificiellement contrainte. Nous avons examiné les effets d'un conditionnement inhibiteur appliqué par rTMS en regard de l'AMS sur l'excitabilité corticophrénique. Nous avons observé la présence d'une diminution persistante de cette excitabilité et en avons tiré la proposition qu'en ventilation de repos l'AMS augmente l'excitabilité de la commande ventilatoire à l'éveil. Nous avons alors considéré les conséquences de la rTMS sur la ventilation expérimentalement contrainte. Les modifications du profil ventilatoire induites par la rTMS sont en faveur d'une participation de l'AMS à la production ou au traitement de la copie d'efférence. Dans une 3ème étude, nous avons examiné les effets de la tsDCS au niveau C3-C5 sur l'excitabilité corticophrénique et sur le profil ventilatoire. L'augmentation de cette excitabilité et du volume courant nous a conduit à suggérer la possibilité d'induire une plasticité respiratoire au niveau spinal.L'ensemble de ces résultats nous permet d'envisager des perspectives thérapeutiques à l'utilisation de la rTMS et de la tsDCS.

Deficits in interval timing have been described in focal brain lesions and in various neuropsychiatric disorders including Parkinson's disease (PD). The aim of this study was to explore brain areas responsible for human time perception and for the timing deficit in PD. We used a time reproduction task (TRT) which consisted of an encoding phase (during which visual stimuli of durations from 5 to 16.6 sec were presented) and a reproduction phase (during which interval durations were reproduced by a button pressing). In our first fMRI study, we used a parametric modulated analysis searching for brain areas with activity, expressed as Blood Oxygenation Level Dependent (BOLD) signal, correlated with the duration of time interval. During the encoding phase, there was a gradual deactivation of the left prefrontal cortex (PFC) and cingulate gyrus. During the reproduction phase, there was a gradual deactivation in precuneus and an accumulation of activity in the left PFC, primary motor area, right caudate and supplementary motor area (SMA). The second study aimed at supporting the role of two of these areas, SMA and precuneus in interval timing by repetitive transcranial magnetic stimulation (rTMS). Accuracy and variability of time estimates were compared before and after rTMS. Accuracy of estimates was not...

Deficits in interval timing have been described in focal brain lesions and in various neuropsychiatric disorders including Parkinson's disease (PD). The aim of this study was to explore brain areas responsible for human time perception and for the timing deficit in PD. We used a time reproduction task (TRT) which consisted of an encoding phase (during which visual stimuli of durations from 5 to 16.6 sec were presented) and a reproduction phase (during which interval durations were reproduced by a button pressing). In our first fMRI study, we used a parametric modulated analysis searching for brain areas with activity, expressed as Blood Oxygenation Level Dependent (BOLD) signal, correlated with the duration of time interval. During the encoding phase, there was a gradual deactivation of the left prefrontal cortex (PFC) and cingulate gyrus. During the reproduction phase, there was a gradual deactivation in precuneus and an accumulation of activity in the left PFC, primary motor area, right caudate and supplementary motor area (SMA). The second study aimed at supporting the role of two of these areas, SMA and precuneus in interval timing by repetitive transcranial magnetic stimulation (rTMS). Accuracy and variability of time estimates were compared before and after rTMS. Accuracy of estimates was not...

Introduction: Memory is a complex cognitive process formerly linked to mechanisms of brain plasticity that can be estimated in the left dorsolateral prefrontal cortex (DLPFC) using transcranial magnetic stimulation and electroencephalography (TMS-EEG). Also, cortical thickness in the DLPFC may be a potential proxy measure of brain plasticity as previous literature reports a link between better memory and thicker cortex. However, the link between brain plasticity and memory performance as well as DLPFC thickness remains to be clarified. Methods: Intermittent theta burst stimulation (iTBS) probed plasticity-like mechanisms in the left DLPFC in 17 cognitively healthy participants. TMS-EEG recordings were performed before and after sham and active iTBS to quantify plasticity via transcranial magnetic stimulation-evoked potentials (TEPs). Composite memory scores for each domain (verbal episodic, visual episodic and working memory) were obtained using the Cambridge Neuropsychological Test Automated Battery. Anatomical T1 images were acquired by magnetic resonance imaging and processed by open-source software (CIVET) and the Automated Anatomical Labeling atlas to extract cortical thickness of the DLPFC. All statistical analyses (linear mixed model, Tukey's post hoc test and Pearson's correlations) were completed in R Studio. Results: iTBS resulted in increased TEP amplitude P30 (F= 5.239, p = 0.029), as shown by a significant interaction between condition (iTBS, sham) and time (pre- and post-condition). Specifically, Tukey's post hoc test revealed that the P30 increase was near trending significant post-iTBS compared to pre-iTBS for the active condition (p = 0.166) but not for the sham condition (p = 0.294). A trending significant relationship was observed between the magnitude of P30 change post-iTBS and thicker left DLPFC (r = 0.488; p = 0.108). Lastly, no significant relationships between P30 change and memory performance were observed. Conclusion: These preliminary findings suggest there could be a relationship between increased capacity for brain plasticity and a thicker left DLPFC. To further investigate these relationships, we plan to recruit additional cognitively healthy participants. Our preliminary findings support the foundation for future clinical studies in which DLPFC thickness could be explored as a predictive factor for response to plasticity-targeting iTBS treatment.