This master’s thesis deals with functional magnetic resonance and monitoring of the effect of acquisition acceleration methods on the quality of functional images and observed BOLD signal. The basic principles of magnetic resonance imaging, the explanation of the specifics of functional magnetic resonance and the formation and scanning of BOLD signal are described here. Subsequently, there is the definition of fMRI experiment and description of sequences used for fMRI, focusing on aquisition acceleration techniques. The influence of sequence parameters on image quality and the data processing methods are explained aftewards. The practical part describes the parameters of used sequences, the acquisition procedure and the task for the subject during aquisition. Data from 26 healthy volunteers were obtained and analyzed afterwards. Based on this, the differencesbetween the different sequence variants were evaluated and the initial assumption that the multi-echo acquisition yields better results with faster measurements than single-echo was confirmed.

Les plus fréquentes tumeurs cérébrales primitives chez l'adulte sont les gliomes. Depuis qu'il est établi que la néo-angiogenèse est liée fortement au mécanisme de croissance des gliomes, plusieurs drogues à visée anti-angiogénique ont étés développées et testés comme un traitement complémentaire en plus de radio- et chimiothérapie. De nouvelles approches par IRM ont été développées pour estimer non-invasivement la néo-angiogenèse tumorale in vivo et étudier son retentissement sur la vascularisation du tissu peritumoral. La première partie de cette thèse a permis d'évaluer la valeur pronostique de la mesure du volume sanguin cérébral (VSC) par l'IRM de perfusion pour la survie des patients qui portent un oligodendrogliome ou une tumeur mixte oligoastrocytaire. Les résultats montraient que le relatif VSC mesuré en IRM de perfusion de premier passage apparaissant comme un facteur pronostique pour la suive des patients. La deuxième partie de cette thèse vise à estimer la perfusion basale peri-tumorale par la technique de premier passage ainsi que la vasoréactivité peri-tumorale par la technique de l'IRMf lors d'inhalation de carbogène, pour évaluer les mécanismes pathophysiologique des altérations du signal BOLD à proximité des tumeurs cérébrales primitives. Les résultats indiquent que l'altération de perfusion basale ne peut pas expliquer le déficit de l'activation motrice au niveau du cortex moteur primaire. La réponse BOLD au carbogène était le meilleur facteur pour expliquer l'asymétrie de l'activation motrice.

Patients with Amyotrophic lateral sclerosis (ALS) often experience cognitive impairment that accompanies degeneration of the motor system. A valuable tool for assessing cognitive control over behaviour is the antisaccade task which requires: 1) inhibition of the automatic response to look towards an eccentric visual stimulus (prosaccade) to instead 2) redirect gaze in the opposite direction of the stimulus (antisaccade). Psychometric tests were used to quantify the degree of impairment, while eye tracking, functional magnetic resonance imaging (fMRI) and structural MRI were combined to identify the neural correlates of cognitive impairment in ALS. We predict ALS patients will have executive dysfunction and grey matter loss in executive and oculomotor control areas that will affect antisaccade performance and will alter the corresponding brain activation. ALS patients and age-matched controls participated in a rapid-event-related fMRI design with interleaved pro- and antisaccade trials. Catch trials (no stimulus presented after instructional cue to prepare pro- or antisaccade) allowed us to discern the preparatory period from the execution period. ALS patients were biased towards automatic saccade responses, and had greater difficulty with antisaccades relative to controls in terms of correct and timely responses. We found that worsened antisaccade performance in ALS correlated with the degree of cognitive impairment. Generally, we found trends of increased brain activation during the preparatory period of antisaccades in ALS patients compared to controls in most oculomotor areas; meanwhile few differences were seen during execution. Structural analyses revealed ALS patients had decreased grey matter thickness in frontotemporal and oculomotor regions such as the frontal and supplementary eye fields (FEF, SEF) and the dorsolateral prefrontal cortex (DLPFC). These findings suggest that loss of structural integrity and executive dysfunction may elicit compensation mechanisms to improve functional and behavioural performance. Despite this compensation, ALS patients still performed worse on antisaccades than controls. Further investigation to expand the current data set should improve our ability to assuredly identify the neural correlates of cognitive decline in ALS, and may provide a model system to use for critical evaluation of future therapies and interventions for ALS. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2011-09-22 14:20:39.704

Parkinson’s disease (PD) is next to Alzheimer’s disease (AD) the second most common neurodegenerative disease. PD has traditionally been characterised as a motor disorder, but more recent research has revealed that cognitive impairments are frequent. Cognitive impairments in executive functions, attention, and working memory with reliance on dopaminergic transmission, are often described as dominating the cognitive profile in early-phase PD. However, although knowledge about the neuropathology that underlies the cognitive impairments in PD has increased, its features are complex and knowledge remains insufficient. Therefore, the aim of the current thesis was to improve the understanding of how task-evoked brain responses relate to cognitive status in patients with PD, with and without mild cognitive impairment (MCI), and to evaluate the predictive value of PD-MCI in respect of prodromal Parkinson’s disease dementia (PDD). This was conducted within the “new Parkinsonism in Umeå” (NYPUM) project, which is a prospective cohort study. Patients with idiopathic PD were included in this thesis, and the patients were examined with a comprehensive neuropsychological battery and with a functional MRI (fMRI) working memory protocol. During scanning, patients conducted a verbal two-back task in which they needed to maintain and actively update relevant information, and the primary outcome measure was blood-oxygen-level-dependent (BOLD) signal. This thesis shows that patients with PD-MCI had significantly lower BOLD signal responses than patients without MCI in frontal (anterior cingulate cortex) and striatal (right caudate) regions (Study I). The altered BOLD response in the right caudate was associated with altered presynaptic dopamine binding. The fronto-striatal alterations persisted across time but without any additional change. However, decreased posterior cortical (right fusiform gyrus) BOLD signal responses were observed in patients with PD-MCI relative to patients without MCI across time (Study II). Finally, PD-MCI at baseline examination is highly predictive for prodromal PDD with a six-fold increased risk. Cognitive tests with a posterior cortical basis, to a greater extent, are predictive for prodromal PDD than tests with a fronto-striatal basis. The observed working memory related alterations in patients with PD-MCI suggest that early cognitive impairments in PD are linked to fronto-striatal dopaminergic dysfunction. The longitudinal development of cognitive impairment in PD reflects additional posterior cortical dysfunction. This might reflect a dual syndrome, with dopamine-depleted fronto-striatal alterations that characterise PD-MCI in general, whereas additional posterior cortical cognitive alterations with a non-dopaminergic basis to a greater extent characterise prodromal PDD. If, and how, the two potential syndromes interact, is still unclear. Thus, this thesis provides information on cognitive neuropathological changes in PD that might contribute to more relevant choices of pharmacotherapy and diagnostic accuracy in respect of PDD. However, additional large-scale longitudinal imaging studies are needed to further clarify the neuropatholgogical features of PD-MCI in respect of prodromal PDD.

Thesis (Ph. D.)--Dept. of Botany, University of Adelaide, 1991. / Typescript (Photocopy). Includes bibliographical references (leaves 166-189).

Changes in the metabolic state of the brain can occur, for example, as a result of neuronal activity or in pathologies such as cancer. In these cases, an altered energy demand can lead to changes in neurochemical concentrations detectable using proton magnetic resonance spectroscopy (¹H-MRS). This thesis explores in vivo ¹H-MRS methods for detection of such changes in the healthy and diseased brain. Specifically, this thesis aims to develop methods with semi-LASER localisation, thereby minimising the negative effects of chemical shift displacement and field inhomogeneity on spectral acquisition. Firstly, a Hadamard-encoded semi-LASER method for simultaneous measurement from two regions was developed at 7 T. Slice profiles, with low chemical shift displacement and small amounts of signal overlap, were revealed in phantom and in vivo. This was then implemented in a study of neurochemical change during positive and negative blood oxygen level-dependent (BOLD) responses. Negative BOLD responses are thought to reflect regions of neuronal suppression. A small decrease in ascorbate, as well as the T2*-induced linebroadening of several spectra, were observed in these regions. Furthermore, increases in glutamate and lactate were detected in positive BOLD regions. These findings suggested that negative BOLD may not be generated by an increase in local GABA concentration. Secondly, an optimised semi-LASER sequence (TE = 110 ms) at 3 T was shown to improve localisation of the oncometabolite 2-hydroxyglutarate (2-HG) - a product of IDH-mutation found in the majority of gliomas. This resulted in improved detection of 2-HG in patients compared to an existing technique. The method was also compared to 7 T, where benefits of an increased spectral resolution resulted in significantly better detection of 2-HG along with associated metabolites. This thesis highlights the importance of robust localisation for performing sensitive in vivo ¹H-MRS neurochemical measurement in the human brain.

Due to abnormal functioning of the brain’s reward and prediction system patients with schizophrenia spectrum disorders are thought to assign salience to non-relevant objects and events and to form context-inappropriate associations. The brain’s ventral striatum is critical in the formation of associations, and aberrant associations are believed to create delusional content during psychosis. The study wanted to examine the neural response, particularly in the ventral striatum, combined with subjective reports as patients learn associations in an aversive Pavlovian conditioning paradigm. The stimuli were randomized and involved circles of different colors. The conditioned stimuli (CS+) was followed by an unconditioned stimuli (US), consisting of an unpleasant sound, in 50% of events. The unconditioned (CS-) stimuli was followed by a low, not unpleasant sound in 50% of events. The degree of striatal activation was thought to be associated with the severity of patient’s illness. Functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) responses were examined in eleven unmedicated non-institutionalized patients with schizophrenia spectrum disorders and 15 matched healthy controls. No significant within group differences in neural or subjective response to the [CS+ > CS-] contrast were found. No significant associations between severity of illness and degree of striatal activation in response to CS+ or CS- were found. Significant differences in neural activation for the [CS+ > CS-] contrast were found in the ventral striatum, the right inferor frontal gyrus, and the right angular gyrus, with patients exhibiting stronger activation compared to controls. The results and implications are discussed along with suggestions for future research.

Abstract Functional magnetic resonance imaging (fMRI) has become a leading tool in the evaluation of the human brain function. In fMRI the activation induced blood oxygenation changes in the brain can be detected with an inherent blood oxygen level dependent (BOLD) contrast. Even small blood oxygen fluctuations in a resting brain can be depicted with the BOLD contrast. This thesis focuses on characterizing spontaneous oxygenation fluctuations of the brain by using BOLD fMRI. The effects of anesthetics on blood oxygen fluctuations were assessed in 38 children and 12 adults. The spatial distribution, frequency, synchrony, and statistical independence of the spontaneous oxygenation changes were analyzed. The role of imaging artifacts in the generation of BOLD signal fluctuations was investigated. The study aimed to develop and compare methods of detecting the nondeterministic oxygenation fluctuations of the brain. VLF BOLD signal fluctuation in the brain cortex is induced by physiological oscillation instead of imaging artifacts. This study shows for the first time how the power and synchrony of very low frequency (VLF <  0.05 Hz) blood oxygen fluctuation significantly increases after sedation. In deeper anesthesia, the VLF fluctuation overpowers other sources of blood oxygen variation as a sign of reduced blood flow and altered hemodynamic control. Regional hemodynamic mechanisms induce non-Gaussian features on the VLF blood oxygen fluctuation that can be depicted effectively with independent component analysis. Combined use of frequency, time, and spatial domain analysis guarantees a more complete picture of brain oxygenation fluctuations. The results of this thesis have a dualistic impact on fMRI research. First of all, VLF fluctuation alters the BOLD activation and connectivity results after sedation. Thus it has to be accounted for in the fMRI of sedated subjects. Secondly, by using the methods developed in this thesis, VLF fluctuation and other physiological BOLD signal sources can now be used in characterizing physiological alterations and pathology of the brain.

La culture de cour au XVe siècle impose au prince de se donner à voir à ses sujets, il se doit d'être magnifique et d'afficher sa puissance. C'est ainsi que Charles le Téméraire, duc de Bourgogne (1467-1477), conçoit son image et se donne en représentation. Dans une cour réputée pour son faste excessif et une étiquette toujours plus stricte, l’habillement est pensé pour valoriser le prince et souligner sa supériorité. L’habillement devient le support d’une identité princière et permet de véhiculer des messages politiques. Le vêtement devient un outil de propagande princière utilisé lors de manifestations publiques telles que les entrées princières, les funérailles et les festivités diverses. Par une approche anthropologique et historique, cette recherche a pour objectif de l’étude de l'usage politique du vêtement à la cour de Bourgogne sous le règne de Charles le Téméraire. La typologie de l'habillement princier et des nobles de la cour et l'étude des usages vestimentaires lors de diverses festivités publiques, cette recherche met également en évidence le contrôle qu’exerce le prince sur son apparence et sur celle des membres de sa cour par l’observation stricte d’une étiquette vestimentaire. / The court culture of the fifteenth century requires the prince to give himself to see his subjects, he must be beautiful and show his power. This is how Charles the Bold, Duke of Burgundy (1467-1477), conceives his image and gives himself in representation. In a court known for its excessive pomp and an ever stricter etiquette, the clothing is thought to value the prince and emphasize his superiority. Clothing becomes the support of a princely identity and conveys political messages. The garment becomes a tool of princely propaganda used during public events such as princely entrances, funerals and various festivities. By an anthropological and historical approach, this research aims to study the political use of clothing at the court of Burgundy under the reign of Charles the Bold. The typology of princely clothing and court nobility and the study of dress habits at various public festivities, this research also highlights the control exercised by the prince on his appearance and on that of the members of his court by strictly observing a clothing etiquette.

The main task of this work is to design an algorithm for suppressing unwanted noise and artifacts in fMRI data using the analysis of independent components and multi-echo data. The theoretical part deals with the basic principles of magnetic resonance, including construction and image data processing. The practical part presents a pilot design of a method inspired by a professional publication in the Matlab software environment, where this design is subsequently tested on real fMRI data provided by the Laboratory of Multimodal and Functional Imaging, CEITEC MU.