Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Thesis (M.Eng.). / Written for the Dept. of Biomedical Engineering. Title from title page of PDF (viewed 2008/05/13). Includes bibliographical references.

Thesis (Ph. D.)--Duke University, 2008. / Includes bibliographical references.

Thesis (M.S. in Electrical Engineering)--Vanderbilt University, May 2005. / Title from title screen. Includes bibliographical references.

La vision classique et hiérarchique de l’organisation du système moteur est remise en question par la découverte d’autres structures que le cortex moteur primaire capables d’influer en parallèle sur la sortie motrice, dans le cadre d’un modèle hodotopique. L’objectif de ce travail a été d’étudier les réseaux de contrôle du mouvement à l’aide de stimulations électriques directes cérébrales lors de chirurgies en condition éveillée pratiquées pour l’exérèse de tumeurs cérébrales. Cette méthode permet la préservation de la fonction motrice tout en apportant de nombreuses informations sur l’organisation du système moteur en général. Le contrôle moteur a été étudié au travers du phénomène moteur négatif, qui consiste en un arrêt du mouvement sans perte de tonus ou de conscience lors d’électrostimulations. Décrit initialement au niveau cortical, nos travaux ont montré qu’il était possible d’identifier ce phénomène dans la substance blanche de façon bilatérale et que les fibres supportant ces réponses motrices négatives sont organisées d’une manière somatotopique, à l’instar de la voie pyramidale. Nous avons pu mettre en évidence une voie modulatrice motrice bilatérale capable d’inhiber les mouvements des deux membres supérieurs lors d’une stimulation sous-corticale unilatérale. Nous avons montré qu’une lésion des sites générant des réponses motrices négatives conduisait à un syndrome de l’aire motrice supplémentaire et à des troubles définitifs des mouvements fins et de la coordination bimanuelle. Ces résultats expliquent les troubles observés lors de chirurgies des régions prémotrices réalisées sans cartographie motrice active, c’est-à-dire cherchant uniquement à identifier les structures motrices primaires. Ils valident la nécessité de pratiquer une cartographie motrice en condition éveillée et ce quelle que soit la dominance hémisphérique. Ces résultats à l’échelle sous-corticale nous ont conduit à définir le concept de réseau moteur négatif et son implication dans les réseaux de contrôle moteur. Le preuve de l’existence de tels réseaux nous a permis d’explorer le niveau cortical et de mettre en évidence une organisation systématique des aires motrices négatives, proposant ainsi une autre vision que celles d’une répartition aléatoire ou somatotopique. Cette organisation en plusieurs aires effecteurs-dépendantes et redondantes a permis de confirmer par les stimulations électriques directes la ségrégation du gyrus précentral en plusieurs gradient rostro-caudal et dorso-ventral. L’ensemble de ces éléments nous a permis d’émettre plusieurs hypothèses concernant le rôle de ces réseaux. Nous supposons qu’il s’agit de plusieurs réseaux interconnectés fonctionnant à l’aide de mécanismes inhibiteurs internes, dont le rôle va de la modulation du flux moteur dans le cadre de processus décisionnels compétitifs intégrés aux aires négatives à l’inhibition vraie d’un comportement moteur dans le cadre de circuits entre le cortex et les noyaux gris centraux. La carte probabiliste réalisée permettra de planifier les chirurgies cérébrales mais aussi de servir de zone d’intérêt pour les nouvelles thérapies par stimulations et la recherche en neurosciences. / The classical and hierarchical view of the motor system has been challenged since the discovery of other structures able to modulate the motor output in the framework of a hodotopic model. The aim of this work was to study the motor control network thanks to direct electrostimulations performed during awake surgery for brain tumors. This method has shown its effectiveness to preserve motor functions while giving new highlights about the organization of the motor system. In our work, motor control has been studied through the negative motor phenomenon, which consists in a complete arrest of movement without loss of tonus or consciousness during electrostimulations. Initially described at a cortical level, our work demonstrated the possibility to elicit negative motor phenomenon in both hemispheres at a subcortical level. Moreover, we identified a bilateral modulatory motor pathway able to inhibit both upper limbs during unilateral subcortical stimulations. We also shown that fibers driving negative motor responses are organized in a somatotopic manner, like the pyramidal pathway. Resection of these fibers lead to a supplementary motor area syndrome with permanent deficit in fine motor skills and bimanual coordination. These results explain the neurological deficits which might occur after surgery in premotor areas when no active brain mapping is performed, that is, when only primary motor structures are sought. They emphasize the necessity to perform a motor mapping during awake surgery whatever the side and hemispheric dominance. These subcortical results led us to define the concept of negative motor networks and their involvement in motor control networks. Evidences of this network allowed us to explore the cortical level and to report a well-defined organization of the negative motor area, different from the random or somatotopic distributions previously described. This effector-dependent and redundant organization in several areas defined by direct electrostimulations has been helpful to confirm the rostro-caudal and dorso-ventral segregation of the precentral gyrus. Consequently, it was possible to propose several hypothesis about the role of these networks. We presume that they are constituted by several large-scale interconnected networks, based on internal inhibitor mechanisms, whose role goes from modulation of the motor output in a competitive model of decision-making integrated in the negative motor area to real inhibition of motor behaviors thanks to cortico-basal ganglia circuitry. The probabilistic map created with these works will be helpful to plan surgery but could also provide regions of interest for brain stimulations therapies as well as neuroscientific research.

Pain and traumatic stress symptoms occur immediately after injury caused by a traumatic event, severities of acute symptoms are associated with risk of development of post-traumatic stress disorder (PTSD) and chronic pain following injury. Deficits in fear-associated learning may contribute to the development of these disorders. A fear associated learning task (FALT) has revealed altered brain activations in patients with PTSD and chronic pain; however, FALT brain activations have not been studied in the early post-trauma period. This study examined FALT brain activation within weeks after traumatic injury to investigate this issue. Within 2 weeks after a traumatic injury, 51 trauma survivors underwent a FALT, comprised of acquisition, extinction, and extinction recall phases during functional magnetic resonance imaging (fMRI). Symptoms were assessed with the PTSD Check List (PCL), Acute Stress Disorder Questionnaire (ASDQ), Pain Anxiety Symptom Scale (PASS20), Pain Catastrophizing Scale (PCS), and the National Pain Score (NPS). Contrast between conditioned stimuli that were (CS+) or were not (CS-) paired with an aversive stimulus revealed activations in the medial-prefrontal (mPFC)/dorsal anterior cingulate (dACC), right insula, and right dorsolateral prefrontal cortices (dlPFC) during acquisition; bilateral sensorimotor, right dlPFC and superior lateral-occipital/superior parietal cortices during extinction; left insular and right lateral occipital cortices during recall. Negative correlations were significant between mPFC/dACC activation during acquisition and both PASS20 and PCS scores. The results suggest emotion regulatory regions are associated with pain stress symptoms within weeks following trauma. These deficits may contribute to development of symptoms of both PTSD and chronic pain. Further studies will examine the relationships between FALT activations and other symptoms.

Com intuito de avaliar o processo cognitivo cerebral e o desempenho de médicos veterinários especializados em radiologia, este estudo proporcionou, através de um sistema computacional, tarefas de questões radiológicas. Os 29 voluntários foram divididos por gênero: homens (n=13) e mulheres (n=16); e por tempo de especialidade: iniciantes (n=13), experientes (n=8) e seniores (n=8). Quatorze casos foram selecionados com diferentes níveis de dificuldade a partir de imagens radiográficas de cães e gatos e foram escaneadas e colocadas em um programa chamado Enscer®, adaptado para a realização deste estudo. Os casos eram divididos em três partes, nomeadas, história clínica, imagem radiográfica e decisão diagnóstica. Durante as etapas, foram realizados eletroencefalogramas dos voluntários, que resultaram em mapeamentos cerebrais. Além disso, foi feita avaliação das respostas corretas, incorretas e dos tempos utilizados para as tarefas. Através das avaliações estatísticas dos resultados foi possível concluir que radiologistas veterinários com maior tempo de especialidade foram estatisticamente mais rápidos nas tarefas e tiveram melhor desempenho diagnóstico; voluntários com maior tempo de especialidade ativaram áreas cerebrais diferentes dos menos experientes; o desempenho diagnóstico foi quantitativamente igual em voluntários de ambos os gêneros e o mapeamento cerebral do grupo masculino foi diferente do grupo feminino, mesmo com desempenho igual nas atividades / With intention to evaluate the cerebral cognitive process and the performance of medical veterinarians specialized in radiology, this study provided, through a computerized system, tasks of radiological questions. The 29 volunteers were divided by gender: man (n=13) and woman (n=16); and by time of experience: beginners (n=13), experienced (n=8) and seniors (n=8). Fourteen cases were selected with different levels of difficulty from radiographic images of dogs and cats and had been scanned and processed by a software called Enscer®, adapted for the accomplishment of this study. The cases were divided into three parts, namely, clinical history, radiographic image and diagnostic decision. During the stages the electroencephalography was carried through, which resulted in the cerebral mapping. Moreover, evaluation of the correct and incorrect answers and of the times used for the tasks was made. Through the statistical evaluations of the results it was possible to conclude that radiologists veterinarians with more time of experience had been statistically faster in the tasks and had had better diagnostic performance; volunteers with more time of experience had activated different cerebral areas than volunteer with less experience; the diagnostic performance was quantitatively equal in volunteers of both genders and the cerebral mapping of the masculine group was different of the feminine group, even with equal performance in the activities

The thesis describes research investigating differences between the two hemispheres in automatic and in attentionally controlled processes. It is suggested that the interaction between these two processes may be a source of hemispheric differences. Three different paradigms that each imply different definitions of automatic and attentionally controlled processes are used: A paradigm used to demonstrate illusory conjunctions, a modified priming paradigm and a modified Stroop-task. Converging evidence from all three paradigms indicates that automatic processes are common to both hemispheres. Lateral asymmetries only emerge in attentional effects. For verbal information, selective attention mechanisms in the left hemisphere are found to be selective for left hemisphere items only, whereas right hemisphere mechanisms are sensitive to information from both hemispheres. The right hemisphere appears to be able to give some automatic support to attended verbal processing in the left hemisphere, while the reverse seems to be more difficult. / Arts, Faculty of / Psychology, Department of / Graduate

The dopaminergic neurons form a brain-wide neuromodulatory system affecting reward, addiction, and motor behaviors. Alterations in dopamine signaling have been associated with many brain disorders, including schizophrenia and Parkinson’s disease. Over the last decade, it has been well-established that the dopaminergic system is capable of significant neurotransmitter phenotypic plasticity (NPP), which is defined as the activity-dependent loss or gain of a specific neurotransmitter usage by neurons. However, most of the related studies have focused on specific regions, providing important but limited insights into NPP. Attaining an unbiased mapping of brain-wide NPP and its relationship with behavioral changes has remained challenging. In this thesis, we first addressed the technical challenges by establishing a whole-brain phenotyping pipeline. Next, we utilized these tools to generate the first brain-wide map of NPP in response to chronic exposure to (R,S)-ketamine, revealing some of the underlying fundamental principles. Here, we describe a whole brain NPP mapping pipeline for studying dopaminergic phenotypic plasticity following chronic (R,S)-ketamine exposure. The pipeline includes 1) an optimized whole brain tissue clearing/immunostaining method for labeling the dopaminergic neurons by utilizing rate-limiting marker tyrosine hydroxylase (TH), 2) high-resolution whole-brain imaging with CLARITY optimized light-sheet microscopy (COLM) and light sheet theta microscopy (LSTM), and 3) a custom python-based data analysis pipeline for quantitative mapping of the brain-wide NPP. Our first key result is that chronic (R,S)-ketamine administration leads to divergent brain-wide changes in the dopaminergic system. Specifically, ten days (but not 1 or 5 days) of daily (R,S)-ketamine (100 mg/kg) administration resulted in a significant decrease in TH+ neurons in regions of the midbrain and a significant increase in areas of the hypothalamus. Second, chronic (R,S)-ketamine treatment also induced an increase in TH+ neuronal projections, including increases within associative cortical brain regions such as the prelimbic area, orbital area, and anterior cingulate area. Decreases in the density of TH+ neuronal projections were observed in the auditory (AUDd) and visual cortices (VISpl). Third, we performed mRNA expression mapping and before-after treatment comparison of the TH+ neuron population within the same animal to reveal that newly gained TH+ neurons are mainly recruited from the neuron pool that contained untranslated TH mRNA. Overall, this thesis provides a first brain-wide quantitative survey of the NPP caused by a specific drug (R,S)-ketamine, extending our fundamental understanding of the extent of adaptability of our brain in response to external stimuli.

Title: The usage of qi-gong for training of perceiving body schema Summary: The goal of the work is to prove the presence of alpha activity in the electroencencefalographic record throughout the duration of the exercise qi-gong with open eyes and closed eyes, and to evaluate changes in the distribution of the scalp alpha activity with native EEG before and after the exercise. The observed research file was created from five probands between the ages of twenty-seven to fifty-two, which all practiced qi-gong for a duration of at least twelve months. The results showed the presence of alpha activity during exercising qi-gong with closed eyes in four probands, and in three probands there was also a present alpha activity during the exercise of qi-gong with open eyes. Furthermore was proven that the change in distribution of alpha activity during exercise of qi-gong with open eyes was from parietooccipital regions going temporo-frontally in comparison with the exercise of qi- gong with closed eyes and native EEG before and after exercise. The acquired results support in literature the described change of generators of alpha activity localized in the deeper structures of the brain. This process is connected with the decreased activity of the cerebral cortex with an increase in the particular limbic structures....