The proportion of older adults living with cognitive impairments is increasing rapidly. This shift will likely increase mortality rates, reduce perceived quality of life, and cause economic burden to patients and health care systems. Currently evidence of highly effective and noninvasive interventions that prevent or slow the onset of cognitive impairment are limited. This study aims to better understand what drives cognitive aging variability among musicians versus non-musicians. Music playing has been shown to improve brain and cognitive functions by engaging networks of brain areas, simultaneously involving cortical mechanisms associated with executive, high-level cognitive and motor functions, and multiple sensory systems. Literature suggests strong correlations between cognition and music ability. However, studies in the past have not concretely operationalized music training. Here we test the general hypothesis that music training improves neural mechanisms associated with core cognitive functions (e.g. working-memory and attention). A multi-source study was designed to control level of music involvement and genre by examining professional, classically trained orchestral musicians, establishing cognitive and neuropsychological profiles in an effort to better understand the potential for music training to protect older adults from cognitive decline. Specific hypotheses involved attentional inhibition theory and increased ability of musicians to perform attention and working memory tasks. Twenty-nine professional musicians were recruited who completed five neuropsychological exams. The scalp electrophysiological signals from 14 channels were recorded wirelessly while each musician performed a modified delayed match-to-sample task, imagination of music playing, and resting states. Musicians completed neuropsychological screening (MoCA) a music and life span questionnaire as well. Musicians tested above normative ranges in cognitive ability indicated through MoCA. Musicians’ scores were compared with average or normative scores of participants at similar ages in previous studies using the same measures and current musicians performed significantly faster and more accurately on four of five neuropsychological measures. Regression and ANCOVA showed strong positive correlations between theta oscillation in bilateral frontal sites (F3, F4) and both number of years of private music lessons and number of hours of music practice. Correlations between EEG recordings taken during music imagination exercise at posterior (01, 02) sites and the number of years of private music lessons participants took, the age participant started to take music lessons and the number of years they played their musical instrument were found. Current new findings reveal that professional musician’s cognitive scores and neural activity are associated with superior cognitive ability via enhancement of neural mechanisms of current target material and inhibition of distractions. Music training is apromising noninvasive method to control cognitive challenge, which merits further research to determine how it can be used as a beneficial cognitive training method for aging individuals. Future studies should examine neuro-cognitive differences between professional musicians and individuals with lower levels of music involvement to examine dose effects of music or the amount of music needed to protect aging adults from cognitive decline.

The aim of this doctoral thesis was to study neuropsychological function in relation to structural and functional brain changes in Alzheimer´s disease (AD). In the first study relations between hippocampal volume, neuropsychological function and limbic-hypothalamic-pituitary-adrenal (LHPA) axis disturbances in AD were investigated with magnetic resonance imaging (MRI). Reduced hippocampal CA1 volume and suppressed cortisol levels in combination, best predicted the variation in neuropsychological performance. The conclusion was that reduced hippocampal volume and LHPA axis disturbances are associated to level of cognitive function in AD. The second study focused on whether patients with early AD showed an altered regional cerebral blood flow (rCBF) pattern compared to control persons, correlation between performance on memory tests and rCBF in sub-lobar volumes of the brain were investigated. The rCBF was measured with single photon emission computed tomography (SPECT). AD-patients showed a significantly lower rCBF in temporoparietal regions including left hippocampus compared to controls. The diagnostic sensitivity and specificity for AD was high in temporoparietal regions. AD-patients had significantly lower performance on semantic and, in particular, episodic memory-tests compared to the controls, and their performance on several episodic tests correlated with rCBF in parietal and temporal regions including left hippocampus, which suggest that abnormalities in the rCBF pattern underlie impaired episodic memory functioning in AD. The conclusion was that an observer-independent analyzing method for SPECT with sub-lobar volumes VOI´s is promising in the diagnosis of AD. In a third study possible differences in memory-related functional brain activation between persons with high versus low risk for AD were examined with functional magnetic resonance imaging (fMRI). The high-risk individuals performed worse than low-risk individuals on tests of episodic memory. Patterns of brain activity during episodic encoding and retrieval showed significant group differences. During both encoding and retrieval, the low-risk persons showed increased activity relative to a baseline condition in prefrontal and hippocampal brain regions that previously have been implicated in episodic memory. By contrast, the high-risk persons did not significantly activate any prefrontal regions, but instead showed increased activity in visual occipito-temporal regions. The conclusion was that patterns of prefrontal brain activity related to episodic memory differed between persons with high versus low risk for AD, and lowered prefrontal activity may predict subsequent disease. In a final study SPECT was used to map patterns of rCBF in an activated state (an episodic encoding task) and in a rest condition in persons with mild AD and in healthy elderly control persons. A reduction of rCBF in temporoparietal regions that was more pronounced in mild AD in the activated encoding task was observed. The conclusion was that there are rCBF differences between mild AD patients and healthy controls in temporoparietal regions, and the temporoparietal reduction is more pronounced during activation than during rest which might be important in the early diagnosis of AD. Taken together, these findings show that level of neuropsychological function, notably episodic memory, can be systematically related to functional disturbances in the LHPA axis and to the function of temporoparietal and prefrontal brain regions in AD patients. These changes are detectable in patients with risk for AD and in an early phase of AD which suggests that the obtained results might be important for early diagnosis of AD.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal

This thesis is an exploratory study of the factors that account for the construction of a local social world around a frontier medical technology. The analysis is based on participant-centred accounts of the structuring of a PET world in the MNI&H. According to local actors, the following factors can be identified to have played a role in the birth, promotion, structuring, and maintenance of the local PET world: the personalities; the institution; the resulting tradition; the assessment of PET; the sense of quality; the size of the local PET world and of the institution; elements of the environment such as cost, finding sources, and manufacturers. The data show that the structuration of the PET world in this elitist research cum hospital institution cannot serve as a model for the diffusion of this frontier technology, although the demarcated pattern exhibits some characteristics common with those described in the literature for similar innovations.

There is a big risk that neuroreceptors located in the knee, responsible for our proprioceptive ability, are damaged after an anterior cruciate ligament (ACL) injury occurs. This may cause miscommunication between the neuroreceptors and motoric function in the brain. Due to the brains plasticity, it has been shown that brain activity patterns, presented as blood oxygen dependent level-signal (BOLD-signal), achieved from functional magnetic resonance imaging (fMRI) differs between healthy and injured individuals when performing certain tasks involving knee movement. As there is little consensus on how a proprioceptive test should be performed, a unique test were participants uses blindfold during a knee bending exercise was created at U Motion Lab, Umeå University. A Matlab based general user interface (GUI) was created for evaluation of the proprioceptive test. This GUI is communicating with the third party toolbox SPM12 and performs necessary preprocessing fMRI-image steps for statistical analysis and statistical parametric mapping of the BOLD-signal for both a healthy control- and ACL-injured group. The fMRIimages preprocessed by the GUI were generated by a 3 T GE scanner and the motion data was collected using an eight-camera 3D-motion analysis system. Time events for three different tasks was investigated. These were passive resting, memorizing and proprioceptive events. For both the control (5 participants)- and ACL (2 participants) group the main area of brain activation during the proprioceptive tests occurred in the frontal lobe. For the control group, brain activation was found in the cerebellum anterior lobe which is a possible origin for unconscious proprioception. For the ACL group activation was found in the inferior parietal lobule which involves visuomotor integration. Activation was also found in the inferior frontal gyrus which according to previous studies, may indicate risk-taking/”out of character” decisions. The results of this study indicates that the proprioceptive test seems to be a promising tool for evaluation of proprioceptive ability. However, more subjects need to be included to validate the result of this study.

Cette thèse d’épistémologie et d’histoire des sciences cognitives est consacrée à son niveau le plus général au problème de l’instrument scientifique, parent pauvre de la réflexion sur l’investigation scientifique, et se concentre à titre particulier sur le développement des techniques d’imagerie cérébrale fonctionnelle et leur introduction dans le domaine cognitif au cours des années 1980-1990. Un choix motivé notamment par la nouveauté et l’importance de ce nouvel instrument, dont l’émergence est régulièrement comparée à celle du télescope au moment de la Révolution scientifique du XVIIe siècle. La première partie est ainsi consacrée à une analyse générale de l’instrument scientifique et des problèmes essentiels qu’il soulève. Elle propose un certain nombre d’hypothèses en réponse, et en examine les enjeux théoriques. La deuxième partie défend une interprétation historique de l’émergence des deux technologies d’imagerie fonctionnelle que sont la tomographie par émission de positons et l’imagerie par résonance magnétique fonctionnelle. En reprenant dans le détail certains éléments d’invention et de diffusion de ces techniques, elle montre notamment l’intrication des procédures de validation des instruments et des divers mécanismes scientifiques et sociétaux qui poussent à les développer puis à les utiliser. A la lumière des analyses théoriques et générales de la première, et sur la base de l’interprétation historique de la seconde, la troisième partie est dédiée à l’examen des implications de ces nouvelles technologies d’imagerie sur l’évolution du champ des sciences cognitives et de la reprise de leurs résultats dans d’autres domaines, tant scientifiques que technologiques ou pratiques. A ce double égard, elle défend la thèse générale que l’introduction de l’imagerie agit beaucoup moins comme un facteur de résolution de certaines questions que comme un facteur de déplacement de la problématique et de l’impact théorique et sociétal des sciences cognitives. / At a general level, this dissertation in philosophy and history of cognitive science is devoted to the underestimated problem of scientific instruments. It is focused on some functional brain imaging techniques introduced in the field of cognitive studies during the 1980’s and 1990’s, the impact of such new technologies being sometimes compared to an instrumental revolution, in a way similar to the impact of the invention of the telescope on post-Galilean astronomy. The first part consists in a philosophical and historical analysis of the notion of scientific instrument. In this regard, some issues are raises and some hypotheses are formulated. The second part presents an interpretation of the historical emergence of Positron Emission Tomography and functional Magnetic Resonance Imaging. Dealing with details of the invention and circulation of those techniques, it shows in particular the entanglement of the validation procedures of instruments with the various scientific and societal mechanisms driving to their development and use. Taking its roots in the general analysis of the first part and the historical interpretation of the second part, the third part looks into the impact of the new functional brain imaging technologies on the evolution of cognitive science and the diffusion of its results in other domains. Concerning both cognitive science and larger aspects, it is argued that brain imaging is less a factor of resolution of specific questions than a factor of shifting in the problematics and the theoretical and societal significance of cognitive science.

Functional connectivity is a field within neuroscience where measurements of co-activation between brain regions are used to test various hypotheses or explore how the brain activates depending on a given situation or task. After analysis, the underlying data in the field consists of a n by n adjacency matrix where each cell represents a correlation value between two regions in the brain. Depending on the research question the number of regions and matrices incorporated varies and new visualizations are needed in order to portray them. In this thesis the design of an interactive web based visualization tool for functional connectivity was explored through an iterative design process. The design of the tool was based on existing guidelines, interviews and best practices in data visualization as well as an analysis of current visualization solutions used in functional connectivity. The final concept and prototype uses a network plot for functional connectivity called the connectogram as well as a grouped bar graph to provide an intuitive and accessible way of comparing functional connectivity data by interacting with and highlighting networks and specific network data through direct manipulation. Results of qualitative evaluations of a prototype using data from a concurrent scientific project is presented. The prototype was found to be useful, engaging, easily perceivable and offered an easy and quick way of exploring data sets.

abstract: Electromagnetic fields (EMFs) generated by biologically active neural tissue are critical in the diagnosis and treatment of neurological diseases. Biological EMFs are characterized by electromagnetic properties such as electrical conductivity, permittivity and magnetic susceptibility. The electrical conductivity of active tissue has been shown to serve as a biomarker for the direct detection of neural activity, and the diagnosis, staging and prognosis of disease states such as cancer. Magnetic resonance electrical impedance tomography (MREIT) was developed to map the cross-sectional conductivity distribution of electrically conductive objects using externally applied electrical currents. Simulation and in vitro studies of invertebrate neural tissue complexes demonstrated the correlation of membrane conductivity variations with neural activation levels using the MREIT technique, therefore laying the foundation for functional MREIT (fMREIT) to detect neural activity, and future in vivo fMREIT studies. The development of fMREIT for the direct detection of neural activity using conductivity contrast in in vivo settings has been the focus of the research work presented here. An in vivo animal model was developed to detect neural activity initiated changes in neuronal membrane conductivities under external electrical current stimulation. Neural activity was induced in somatosensory areas I (SAI) and II (SAII) by applying electrical currents between the second and fourth digits of the rodent forepaw. The in vivo animal model involved the use of forepaw stimulation to evoke somatosensory neural activations along with hippocampal fMREIT imaging currents contemporaneously applied under magnetic field strengths of 7 Tesla. Three distinct types of fMREIT current waveforms were applied as imaging currents under two inhalants – air and carbogen. Active regions in the somatosensory cortex showed significant apparent conductivity changes as variations in fMREIT phase (φ_d and ∇^2 φ_d) signals represented by fMREIT activation maps (F-tests, p <0.05). Consistent changes in the standard deviation of φ_d and ∇^2 φ_d in cortical voxels contralateral to forepaw stimulation were observed across imaging sessions. These preliminary findings show that fMREIT may have the potential to detect conductivity changes correlated with neural activity. / Dissertation/Thesis / Doctoral Dissertation Biomedical Engineering 2020

Le but de ce travail est d’étudier deux dimensions sémiologiques, identifiées dans la littérature comme associées au trouble dépressif résistant, l’anxiété et l’apathie. Ces marqueurs cliniques et leurs corrélats radiologiques seront ensuite testés dans une analyse longitudinale du pronostic à 6 mois d’une cohorte de patients souffrant de dépression. Les données originales de ce travail sont issues de la cohorte LONGIDEP. Cette étude prospective, naturalistique, a été menée chez des patients souffrant d’un épisode dépressif majeur qui bénéficiaient, dans le cadre des soins courants, d’une évaluation clinique, neuropsychologique et d’une imagerie cérébrale à l’inclusion. Une nouvelle évaluation a été proposée à 6 mois de l’inclusion. Cette étude nous a permis de montrer que 1) l’apathie dans la dépression est associée à un profil clinique et physiopathologique spécifique, 2) l’analyse catégorielle et sémiologique de l’anxiété dans une population de sujet déprimés résistants n’étaient pas concordantes. Les déprimés résistants présentaient une hyperperfusion amygdale centro-médiane, 3) l’anxiété trait, un pattern cognitif associé à la mémoire visuo-spatiale étaient prédictifs d’une évolution péjorative de la dépression. Des anomalies structurales de régions impliquées dans la régulation émotionnelle et plus précisément l’adaptation au danger/peur, étaient associées à une évolution péjorative de la dépression. Des deux dimensions sémiologiques étudiées, l’anxiété apparaît être impliquées dans le pronostic de la dépression. L’étude des liens entre l’anxiété et les troubles de la motivation est une perspective de recherche pour la dépression résistante. / The aim of this work is to study anxiety and apathy in treatment resistant depression. These clinical factors and its imaging correlates will be tested in prediction of outcome in a 6-months follow-up. Original data were retrieved in LONGIDEP cohort. This is a prospective study conducted in routine care. Patients suffering from a mood depressive episode benefited from a clinical, neuropsychological and brain imaging. They were assessed once again at 6 months. Our study has shown that 1) apathy in depression is associated with specific clinical and pathophysiological patterns, 2) categorical and dimensional approach of anxiety in treatment resistant depression are not convergent. This latter population exhibited higher brain perfusion of centro-medial amygdala, 3) trait anxiety, cognitive patterns of visuospatial memory were predictive of pejorative outcome. Structural abnormalities in key regions involved in emotion regulation were associated with pejorative outcome of depression. Only anxiety was involved in outcome of depression. The link between anxiety and motivation should be studied in further works.

Ce travail est conçu dans le panorama de développement rapide de grandes bases de données qui rassemblent des ensembles de résultats expérimentaux sur l’organisation anatomo-fonctionnelle du cerveau humain à différentes échelles; l’abondance d’informations demande un effort intra et interdisciplinaire pour les synthétiser de façon cohérente. Le but de cette thèse est de contribuer à cet effort de synthèse. Le travail suit deux chemins: intra disciplinaire pour relier et synthétiser les résultats produits par la communauté de l’imagerie cérébrale, avec une focalisation particulière sur les Réseaux de Repos et les Réseaux Cognitifs; inter-disciplinaire pour relier l’organisation anatomo-fonctionnelle du cortex cérébral (résultats en imagerie cérébrale), et les expressions des gènes révélées par les bases de données publiées très récemment sur le transcriptome humain.Cette thèse est organisée en trois parties: dans Partie I nous étudions l’organisation anatomo-fonctionnelle du cortex à partir des études d’imagerie cérébrale. Dans la Partie II, nous étudions les liens entre l’expression corticale des gènes et l’organisation anatomo-fonctionnelle du cortex, à la fois en termes de similitude topographique et de congruence de fonction, en se focalisant en particulier sur le traitement de l’information et la mémorisation. Dans la Partie III, nous présentons une plate-forme pour intégrer dans une même représentation les données d’imagerie cérébrale et d’expression génétique.En perspective, nous montrons comment notre approche pourrait donner des nouveaux points de vu au débat sur les maladies neurodégénératives et psychiatriques, et sur les modelés des dynamiques corticales. / This work is conceived in the present panorama of fast development of large databases gathering experimental results about the organization of the human brain at different scales. This abundance of information calls for an intra and inter-disciplinary effort aimed to synthesize this information in a coherent way.The aim of this thesis was to contribute to this effort for knowledge synthesis to better understand the multiscale organization of the cerebral cortex. The work followed two paths: an intra-disciplinary effort to bring together results produced by the brain imaging community with particular focus on Resting State and Task Based MRI experiments; an inter-disciplinary attempt to draw a link between the anatomo-functional organization of the cortex as emerging from brain imaging studies and the cortical patterns of gene expression as revealed by recently published atlases of the adult human brain transcriptome.The thesis is organized into three parts: In Part I studied the anatomo-functional organization of the human cortex starting from brain imaging studies. In Part II we studied the link between cortical gene expression and the anatomo-functional organization of the cortex both in term of their topography and in term of their function, focusing in particular on information processing and memory formation. In Part III we present a platform that we developed to favor knowledge integration between cognitive networks and gene expression databases.In perspective we show how our approach may provide new insights to the debate about neurodegenerative and psychiatric diseases on one hand, modeling of dynamical processes in different areas of the cortex on the other.