Orientador: Luiz Eduardo Gomes Garcia Betting / Resumo: Fundamento: Evidências experimentais de modelos animais de crises de ausência sugerem focalidades no início das descargas generalizadas. Estudos clínicos indicam que pacientes com o diagnóstico de epilepsia generalizada idiopática (EGI) exibem anormalidades focais que envolvem o circuito tálamo-cortical no eletroencefalograma (EEG) e na neuroimagem. Objetivos: Investigar a presença de características focais nas descargas generalizadas interictais usando análise quantitativa do EEG (EEGq) e avaliar o córtex do giro do cíngulo usando múltiplas abordagens quantitativas de neuroimagem. Métodos: 75 EEGs de 64 pacientes foram analisados. A primeira espícula generalizada inequívoca foi marcada para cada descarga. Três métodos de análise de fonte geradora da atividade observada foram aplicados: transformação do dipolo em imagem (dipole source imaging-DSI), abordagem LORETA aplicada iterativamente (CLARA), e análise de dipolo equivalente de componentes independentes com análise de agrupamentos. Após processamento do EEG, 32 pacientes (18 mulheres, 32 ± 11) fizeram ressonância magnética. Foram utilizados três métodos para comparar o giro do cíngulo de pacientes e controles: morfometria baseada em voxel (VBM), análise cortical e análise de formato. Resultados: 753 descargas generalizadas foram analisadas. Usando as três técnicas, o lobo frontal foi a principal fonte das descargas (70%), seguido pelos lobos parietal e occipital (14%) e, por fim, os núcleos da base (12%... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Experimental evidence from animal models of absence seizures suggests a focal source for the initiation of generalized spike-and-wave (GSW) discharges. Clinical studies indicate that patients diagnosed with idiopathic generalized epilepsy (IGE) exhibit focal electroencephalographic and subtle structural abnormalities, which involve the thalamo-cortical circuitry. Aims: The objectives of the current investigation were to investigate whether interictal generalized discharges exhibit focal characteristics using qEEG analysis and to perform a comprehensive analysis of the cingulate cortex using multiple quantitative structural neuroimaging techniques. Methods: 75 EEG recordings from 64 patients were analyzed. The first unequivocally confirmed generalized spike was marked for each discharge. Three methods of source imaging analysis were applied: dipole source imaging (DSI), classical LORETA analysis recursively applied (CLARA), and equivalent dipole of independent components with cluster analysis. After EEG analysis, 32 patients (18 women, 30± 10 years) and 36 controls (18 women, 32 ±11 years) were imaged by 3 Tesla magnetic resonance (MRI). We used three models to compare cingulate gyrus of patients and the control group: voxel-based morphometry (VBM), cortical analyses and shape analyses. Results: A total of 753 GSW discharges were spatiotemporally analyzed. Source analysis using all three techniques revealed that the frontal lobe was the principal ... (Complete abstract click electronic access below) / Doutor

The side-effects of chemotherapy treatment are an increasingly important research focus as more cancer patients are reaching survivorship. While treatment allows for survival, it can also lead to problems which can significantly affect quality of life. Cognitive impairments after chemotherapy treatment are one such factor. First presented as anecdotal patient reports, over the last decade empirical evidence for this cognitive concern has been obtained. Much attention has been focused on post-chemotherapy research, yet little attention has been granted to these same patients’ cognition before treatment commences. Breast cancer (BC) patients face many obstacles before chemotherapy treatment such as: surgery and side-effects of anesthesia, increased cytokine activity, stress of a new disease diagnosis and upcoming challenges, and emotional burdens such as depression and anxiety. Many of these factors have independently been shown to affect cognitive abilities in both healthy populations as well as other patient groups. Therefore, the pre-treatment (or baseline) BC patient status warrants systematic study. This would then reduce mistakenly attributing carried-over cognitive deficits to side effects of chemotherapy. As well, it is possible that certain confounding variables may have neural manifestations at baseline that could be exacerbated by chemotherapy agents. The following thesis first presents a review paper which critically describes the current literature examining chemotherapy-related cognitive impairments (CRCIs), as well as possible confound variables affecting this population. Subsequently, three original research papers present pre-chemotherapy data showing significant neuroanatomical and neurofunctional differences in BC patients compared to controls. In particular, these neural differences are present in brain regions that have been reported in post-chemotherapy papers. This, as well as the effects of variables such as the number of days since surgery, depression and anxiety scores and more, support the initiative that research attention should increase focus on these patients at baseline in order to better understand their post-chemotherapy results.

Les progrès dans le domaine de la neuroimagerie cérébrale ont permis une certaine compréhension des maladies mentales comme la schizophrénie. Cependant, peu de résultats sont cohérents et ils sont souvent contradictoires, ce qui rend difficile de tirer des conclusions concrètes par rapport à la maladie. Plusieurs facteurs jouent un rôle dans les résultats divergents et convergents : Les différentes techniques d'imagerie et les analyses, le nombre de patients inclus dans les études, l'âge des patients, l'âge de l’'apparition de la maladie, les critères de diagnostic, les effets du traitement antipsychotique, le statut social, ainsi que les comorbidités, font partie de ces facteurs. Bien que les différences cérébrales entre femmes et hommes « normaux » sont bien établies, ce n’est que ces dernières années que des études en neuroimagerie de la schizophrénie ont abordé les différences homme-femme comme une explication potentielle des résultats discordants de l’imagerie cérébrale. L'objectif de cette thèse est de comprendre le rôle du sexe (genre féminin et masculin) dans les anomalies anatomiques observées dans la schizophrénie; ceci, en réalisant des études qui contrôlent, autant que possible, l'effet de différentes variables confondantes et en utilisant des analyses d’IRM automatisées chez des patients et des sujets sains de même âge et du même sexe. Une brève revue globale des résultats actuels dans le domaine de la schizophrénie ainsi que des résultats liés aux différences entre les sexes dans la schizophrénie vont être présentés. La première étude visait à étudier l'influence des différences de sexe sur des mesures de la gyrification corticale de la schizophrénie. Étant donné que la schizophrénie est une maladie dont les «symptômes cliniques » ont un impact négatif sur la qualité de vie des patients qui en souffrent, nous avons exploré la relation entre la gyrification corticale et les différents symptômes de la schizophrénie chez les hommes et les femmes atteints de ce trouble psychiatrique. Le rôle du sexe sur la gyrification corticale et son association aux symptômes a été à peine étudié chez les patients atteints de schizophrénie ; c’est pour cette raison que, nous croyons que cette étude est d’une importante valeur. Dans cette première étude, des images 3T T1 ont été acquises auprès de 48 patients atteints de schizophrénie (24 hommes [SZ-M] et 24 femmes [SZ-F]) et 48 volontaires sains (24 hommes [NC-M] et 24 femmes [NC-F]), appariés en fonction de l'âge et du sexe. Des mesures d’indice de gyrification (IG) pour chaque hémisphère et les quatre lobes cérébraux (frontaux, temporal, pariétal, et occipital) ont été effectuées en utilisant le pipeline de CIVET, lequel est entièrement automatisé. Plusieurs résultats intéressants ont émergé: les patients avaient des valeurs inférieures importantes de l’IG global par rapport aux témoins; SZ-M avaient des valeurs d'IG hémisphériques significativement inférieurs par rapport à NC-M, cela n'a pas été observé dans les groupes de femmes. Aucune différence entre les sexes dans les valeurs de diminution de l’IG avec l'âge n’a été observés chez les témoins sains par contre, une diminution de la valeur de l’IG avec l’âge chez les patients était plus importante chez les patients homme que les patients femmes. Une détérioration plus progressive dans l'hémisphère droit dans les deux groupes de patients a été observée, tout comme des réductions significatives des valeurs d’IG en relation avec la durée de la maladie chez SZ-M, mais pas chez SZ-F. Dans les groupes de patients, on observe des diminutions des valeurs d’IG dans les lobes frontaux bilatéraux et, le lobe occipital droit; le groupe SZ-M a montré une valeur d’IG significativement plus élevée par rapport à NC-M dans le lobe temporal droit; SZ-F a montré des valeurs d’IG significativement plus faibles dans les lobes bilatéraux frontaux, temporaux, pariétaux et le lobe occipital droit, par rapport à NC-F. Aucune corrélation significative n'a été trouvée entre les valeurs de l'IG et le profil de la symptomatologique dans les deux groupes de patients. Etant donné que l’IG reflète, en partie, des altérations dans le développement et la connectivité cérébrale, la diminution de l’IG observée chez les patients est en accord avec le modèle de développement neurobiologique de disconnectivité dans la schizophrénie. De plus, nous soulignons l'importance de l'âge ainsi que la durée de la maladie lorsque nous comparons les hommes et les femmes atteints de schizophrénie. Cependant, nous n'avons pas observé de corrélation significative n'a été trouvée entre les valeurs de l'IG et les symptômes, ce qui est d'un intérêt particulier et inattendu compte tenu des résultats de la neuroimagerie montrant par exemple certaines corrélations entre les symptômes positifs et certaines anomalies du lobe temporal dans la schizophrénie. Considérant ces résultats, nous avons décidé d'investiguer, dans notre deuxième étude, l'association entre les symptômes et les densités de matière grise (DMG) et de matière blanche (DMB) à la place des mesures de gyrification corticale. Nous avons utilisé la morphométrie basée sur le voxel "Voxel Based Morphometry (VBM8.0 with Diffeomorphic Anatomical Registration (Through Exponentiated Lie Algebra [DARTEL])" et la modélisation linéaire automatique (SPSS21.0 ALM) sur les images 3T T1 MPRAGE acquises auprès de 40 patients atteints de schizophrénie (SZ) et 41 témoins sains (NC). Nous avons trouvé que les patients atteints de schizophrénie avaient une DMG réduite dans le cortex cingulaire antérieur, le cortex temporal médian gauche et une DMG plus élevée dans le cortex cingulaire postérieur gauche par rapport aux sujets sains. Une diminution significative de DMB dans la région fronto-rectal inférieure gauche et la région pariétale postérieure gauche a été observée chez les patients comparés aux sujets sains. Nous avons trouvé des corrélations positives entre les symptômes positifs et la DMG dans l'insula gauche et le noyau caudé droit; et entre les symptômes négatifs et la DMG dans le cortex frontal médian droite et le lobe postérieur de cervelet droit. Nous avons aussi trouvé des corrélations négatives de DMG dans la région pariétale droite (précuneus), le lobe postérieur du cervelet gauche et les symptômes positifs; ainsi qu'entre la DMG du lobe antérieur du cervelet gauche et les symptômes négatifs. En outre, des corrélations positives ont été trouvées entre la DMB dans le cortex frontal médian droit et les symptômes positifs et entre le DMB dans la région frontale supérieure droite et les symptômes négatifs. Des corrélations négatives ont été trouvées entre les symptômes positifs et la DMB dans la région occipitale inférieure droite et le cunéus occipital droit, tandis que des corrélations négatives ont été trouvées entre la DMB et la région frontale supérieure gauche. Il est intéressant de noter que lorsque les symptômes ont été analysés par regroupement, nous avons trouvé que le symptôme de la désorganisation conceptuelle corrélait positivement avec la DMG totale et la DMB totale. L’augmentation de DMG a été associée à une diminution de la gravité des hallucinations et du manque de spontanéité; tandis que l'augmentation de DMB totale a été associée à la diminution de la sévérité de l'hostilité et des idées de grandeur. Une comparaison entre les groupes d'hommes a montré une diminution de la DMG chez les patients schizophrènes, tandis qu’aucune différences n’a été observée dans les groupes de femmes. Nous n’avons trouvé aucune corrélation entre la DMG, la DMB, le liquide cérébro-spinal, le volume total du cerveau, les symptômes individuels et la schizophrénie chez les sujets féminins. Chez les hommes atteints de schizophrénie, on observe des corrélations négatives importantes entre les idées de grandeur et la DMB; des corrélations positives entre la désorientation et la DMB. De plus on observe des corrélations entre et les déficits d'attention et de DMG et DMB. Nos résultats montrent que ces associations sont différentes chez les hommes et les femmes atteints de la schizophrénie. La symptomatologie de schizophrénie est un mélange de déficits cognitifs et socio-affectifs. Dans ce contexte, le but de notre troisième étude est d'étudier chez les patients atteints de la schizophrénie des DMG et DMB et leur relation avec l’acuité mnésique avec des contenus émotionnelles (négatives, positives et neutres) ainsi que étudier l'effet des différences de sexe sur nos résultats. Quarante et un patients droitiers, traités par antipsychotique, souffrant de schizophrénie (SZ) et 40 témoins sains (NC), tous droitiers, ont participé à l’étude. Nous avons utilisé des images de l'International Affective Picture System (IAPS), une banque d'images émotionnelles, et de l’IRM. On observe chez les témoins sains des corrélations entre les valeurs élevées de DMG du cortex pariétal postérieur, du lentiform, du putamen, noyau caudé, le cortex orbitofrontal inférieur gauche et la reconnaissance des images négatives. On observe des corrélations entre la DMG dans la région temporale gauche, fusiforme et la reconnaissance des images positives ; et également dans le cervelet antérieur gauche et l’acuité des images neutres. Chez les patients on observe des valeurs élevées des DMG dans le cortex occipital inférieur gauche et la reconnaissance des images négatives, mais aucune corrélation entre la capacité de reconnaissance des images positives ou neutres. Nous avons observé chez les témoins sains: des relations significatives entre la DMB dans le cortex pariétal postcentral gauche et la capacité de reconnaître des images négatives; dans le cortex temporal inferieur gauche, le cortex pariétal gauche (précuneus), le cortex frontal gauche et la capacité de reconnaissance des images positives; des valeurs de DMB du cortex temporel médian et l’acuité des images neutres. Les patients atteints de schizophrénie ont montré des relations significatives entre de DMB dans le cortex occipito-lingual gauche et la reconnaissance des images négatives ; dans le cortex pariétal angulaire gauche et la reconnaissance des images positives ; et dans le cortex temporal supérieur droit et les images neutres. Les différences de sexe dans la schizophrénie ont été observées : chez les patients de sexe masculin, des corrélations négatives ont été trouvées entre les DMB et la capacité de reconnaître des images négatives et positives. Chez les hommes sains, nous avons trouvé des corrélations positives entre des valeurs totales de DMG et la capacité de reconnaître des images négatives. Nous n’avons pas observé de corrélations dans les groupes de femmes. Ces résultats soutiennent l'hypothèse de l'atrophie fronto-temporale régionale chez les patients schizophrènes. Toutefois, nous notons qu’ils ont des augmentations relatives des valeurs de DMB dans le cortex occipito-pariétal. Nous avançons l'hypothèse que les déficits mnésiques chez les patients sont liés à des perturbations dans la coordination des réseaux cérébraux, ce qui peut être affecté par des déficits structuraux plus évidents chez les patients masculins. Par conséquent, nous préconisons que les futures études devraient utiliser le connectome ou l’approche « réseaux cérébraux » pour étudier l’impact du sexe (genre masculin-féminin) sur les déficits cognitifs et symptomatologiques dans la schizophrénie. Nos résultats globaux soulignent l'importance de la différence entre homme et femme dans la modulation de manifestations cliniques et fonctionnelles de la schizophrénie. Ainsi, nous croyons que le contrôle des covariables comme l'âge, la durée de la maladie et le statut social est insuffisant et que les études futures sur la schizophrénie devraient systématiquement séparer les hommes des femmes, afin de mieux comprendre cette maladie mentale complexe et dévastatrice. / Advances in cerebral neuroimaging techniques have helped our understanding of mental illnesses, such as schizophrenia. Few findings remain consistent and are often contradictory, making it difficult to draw informative conclusions about the disease. Several factors play a role in both diverging and converging results. Imaging technique and analyses, number of patients involved, age of patients, age at onset of the disease, diagnostic criteria, antipsychotic treatment effects, social status, comorbidities, are among some of the reasons. Despite well established cerebral sex differences in healthy population, it is only in recent years that neuroimaging studies in schizophrenia have addressed sex differences as a major possible explanation for discrepant neuroimaging finding. The aim of this thesis is to help understand the role of sex on brain structures in schizophrenia, by conducting studies that control as much as possible for other variables and by using MRI automated analyses for patients and controls matched for age and sex. This work will briefly present findings in schizophrenia in general, and then an extensive review of the literature on sex differences in schizophrenia will be presented. From it, we are able to conclude that sex differences have been reported with rare exception in almost all aspects involved in the life of patients with schizophrenia. Chapters 1. The first study investigated sex differences in cortical gyrification in schizophrenia patients (SZ). In addition, considering that schizophrenia is a disease of “clinical symptoms” that determine the quality of life of patients afflicted by it, we explored the relation between cortical gyrification and symptoms in males and females with schizophrenia. The role of sex on cortical gyrification and its association with symptoms has been scarcely investigated in patients with schizophrenia. In this study, 3T T1 images were acquired from 48 schizophrenia patients (24 males [SZ-M] and 24 females [SZ-F]) and 48 normal controls [NC] (24 males [NC-M] and 24 females [NC-F]) matched for age, sex, and handedness. Gyrification Index (GI) analyses for each hemisphere and four cerebral regions (frontal, temporal, parietal, and occipital) were performed using the fully automated CIVET pipeline. Patients had significant lower values of the overall GI relative to normal controls and SZ-M had significant lower right hemispheric GI values compared to NC-M. This was not observed in either NC-F or in SZ. No gender difference in GI values decreases with age were observed in NC. In patients, GI decreases with age were greater in SZ-M than SZ-F, with a more progressive deterioration in the right hemisphere in both patient groups. Significant GI value reductions in association with duration of illness were observed in SZ-M but not in SZ-F. Patient groups had lower GI in bilateral frontal, temporal, and parietal lobes than controls. SZ-F had significant lower GI values in left frontal, bilateral temporal and left parietal lobe compared to NC-F. No significant correlations were found between GI values and symptom scores in either group of patients. Since GI reflects, in part, alterations in cerebral development and connectivity, the decrease in GI observed in patients is in agreement with the neurodevelopmental model of disconnectivity in schizophrenia, and may explain the worse prognosis and social outcome observed in male patients. Furthermore, we emphasize the importance of age and duration of illness when comparing males and females with schizophrenia. Observed differences between male and female patients may reflect a more diffuse and generalized cortical loss in males. Female patients had cortical loss in specific regions, while preserving cortical gyrification in compensatory regions. Our latter finding -no significant correlation between GI values and symptom scores- was of particular interest and was unexpected in view of neuroimaging findings of correlations between positive symptoms and temporal lobe abnormalities. 2. In the second study, we examined the association between symptoms and brain structure using gray (GMD) and white matter (WMD) densities. Voxel-based morphometry (VBM8.0 with Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra [DARTEL]) and Automatic Linear Modeling (SPSS21.0 ALM) were used on 3T T1 MPRAGE images acquired from 40 schizophrenia patients (SZ) and 41 normal controls (NC). We found that SZ had lower GMD in the anterior cingulate cortex and left middle temporal gyrus, and higher GMD in the left posterior cingulate in comparison to NC. SZ had significantly lower WMD in the left inferior fronto-rectal and the left posterior parietal regions in comparison to NC. Significant positive correlations were found between positive symptoms and GMD in the left insula and right caudate, and between negative symptoms and GMD in the right middle frontal and the posterior lobe of the right cerebellum (uvula). Inverse relationships between GMD in the right parietal (precuneus), the left posterior lobe of the cerebellum (uvula) and positive symptoms, and between GMD in the left anterior lobe of the cerebellum and negative symptoms were observed in SZ. In addition, positive correlations were found between WMD in the right middle frontal lobe, and between positive symptoms and WMD in the right superior frontal region with negative symptoms. Negative correlations were found between positive symptoms and WMD in the right inferior occipital and the right occipital cuneus, while negative symptoms correlated negatively with the WMD of the left superior frontal. When symptom clusters were analyzed, conceptual disorganization symptom positively correlated with both total GMD and WMD. While increases in GMD were associated with decreased severity of lack of spontaneity and hallucinations symptom, increases in total WMD were associated with decreased severity of hostility and grandiosity symptoms. Comparison between male subjects revealed decreased GMD in male schizophrenia patients, while no differences were observed between females across groups. No correlations were found in female groups between GMD, WMD, CSF, or total brain volume and individual symptoms. In males with schizophrenia, significant negative correlation between ideas of grandiosity and WMD, a positive correlation between disorientation and WMD, and attention deficits and GMD and WMD were found. The current data suggest region-specific GMD and WMD association with negative and positive symptoms. In addition, it reveals that such associations are different in male and female schizophrenia patients. 3. The third study investigated the relationships of GMD and WMD with memory accuracy for emotionally negative, positive, and neutral pictures in schizophrenia patients relative to normal controls. Schizophrenia is characterized by an amalgam of cognitivo-socio-emotional deficits. The relationship between emotion processing on cognition and neurobiological underpinnings merit more attention than it has received so far. Memory deficits are among the most common deficits in schizophrenia and have a widespread impact on cognition in general. Additionally, consistently with the major theme of the present thesis, we investigated the effect of gender on the observed effect. Forty one, right-handed medicated patients with schizophrenia (SZ) and 40 right-handed normal controls (NC) matched by age and sex were assessed for memory accuracy using negative, positive and neutral pictures taken from the International Affective Picture System (IAPS). Imaging methods and analyses were similar to our second study. Fifteen minutes after presentation of selected IAPS images (incidental encoding), subjects were asked to recognize the previously seen images among other images. We found higher GMD in NC in the right posterior parietal cortex, lentiform, putamen, and caudate, as well as the left inferior orbitofrontal cortex, in relation with the negative images accuracy. NC had higher GMD in the left temporal and fusiform regions in relation with the positive images accuracy, and higher GMD in the left anterior cerebellum in relation with neutral images. Schizophrenia subjects had higher GMD in the left inferior occipital cortex in relation with the negative images accuracy, but GMD was not correlated with positive or neutral images accuracy in this group. WMDs correlations were higher in NC in the left postcentral parietal region for negative images; in the left inferior temporal, left precuneus parietal, and left frontal regions for positive images; and in the left middle temporal region for neutral images. Schizophrenia patients had higher WMD in the left lingual occipital for negative images; in the left angular parietal for positive images; and in the right superior temporal region for neutral images. While examining the two sexes separately, we observed inverse correlations between WMD and both negative and positive pictures in male patients. In addition, only in male controls, GMD positively correlated with negative pictures and this correlation was absent in female SZ subjects and NC females. These findings support the hypothesis of fronto-temporal regional atrophy in schizophrenia. Schizophrenia patients have relatively increased occipito-parietal WMD, advancing the hypothesis that the core pathophysiological problem underlying recall memory in SZ may be related to disruptive alterations in the coordination of large-scale brain networks, and this may be affected by structural deficits that are more evident in male patients. It is recommended that future studies should use the connectomes or the brain networks approach to investigate the effect of sex on memory deficits in schizophrenia. Our overall findings point out to the importance of sex in modulating the clinical and functional manifestations of schizophrenia. We believe that controlling for covariates as age, duration of illness, social status, etc. is insufficient and that future studies in schizophrenia should systematically separate male and female findings, if we wish to understand this complex and devastating mental illness.

Pathologisches Glücksspiel (PG) ist eine psychiatrische Erkrankung, die gerade erst im DSM-5 der gleichen Kategorie wie substanzgebundene Suchterkrankungen zugeordnet wurde. Bildgebungsstudien zu Substanzabhängigkeit beobachteten funktionelle und strukturelle Veränderungen im präfrontalen Kortex (PFC) und mesolimbischen Belohnungssystem (d.h. Striatum). Für PG wurden ähnliche Veränderungen berichtet; jedoch gibt es kaum Studien, die sich mit verschiedenen Aspekten funktioneller und struktureller Korrelate in diesen Regionen beschäftigen. Diese Arbeit untersuchte PG Patienten, alkoholabhängige (AD) Patienten und Kontrollpersonen (HC) mit Magnetresonanztomografie. In Analyse I wurden funktionelle Gehirndaten während der Belohnungsaufgabe zwischen den drei Gruppen verglichen. In Analyse II wurde das Volumen grauer Substanz mit voxelbasierter Morphometrie und in Analyse III die intrinsische Gehirnaktivität mit einer seedbasierten funktionellen Konnektivitätsanalyse von PG Patienten und HC ausgewertet. Die Analysen ergaben veränderte Aktivierungen in frontostriatalen Arealen während der Verarbeitung von Verlustvermeidung für PG Patienten im Vergleich zu HC. PG Patienten unterschieden sich dabei in ihrer Aktivierung von AD Patienten während der Antizipation von Geldverlust. Weiterhin zeigten PG Patienten erhöhte Volumina grauer Substanz und eine erhöhte funktionelle Konnektivität in frontostriatalen Arealen im Vergleich zu HC. Die Ergebnisse liefern weitere Hinweise für eine veränderte Belohnungsverarbeitung in PG und betonen die Bedeutung der Verlustvermeidungsverarbeitung. Die Volumenveränderungen im und die erhöhte Konnektivität zwischen dem PFC and Belohnungssystem deuten auf eine veränderte Interaktion zwischen diesen Regionen hin. Da solche Veränderungen in kortikostriatalen Systemen Ähnlichkeiten zu denen in Substanzabhängigkeiten aufweisen, unterstützen die Ergebnisse die neue Klassifikation des PG im DSM-5. / Pathological gambling (PG) is a psychiatric disorder newly classified under the same category as substance use disorders in the DSM-5. Neuroimaging studies on substance-related addictions reported functional and structural changes in the prefrontal cortex (PFC) and the mesolimbic reward system (i.e., striatum). For PG, findings are not that extensive, but also demonstrate altered reward processing and prefrontal function. However, there is a lack of studies focusing on different aspects of functional and structural correlates within these areas in PG. This thesis investigated PG patients, alcohol dependent (AD) patients and healthy controls with magnetic resonance imaging (MRI). In analysis I, functional brain data of a reward paradigm was compared between the three groups. In analysis II, local gray matter volume of PG patients and controls was processed via voxel-based morphometry. Resting-state data of PG patients and controls was analyzed via seed-based functional connectivity in analysis III. Results revealed altered brain responses in fronto-striatal areas during loss avoidance processing in PG patients as compared to controls. Importantly, PG patients differed in their brain responses from AD patients during the prospect of monetary loss. Moreover, PG patients showed an increase in local gray matter volume and functional connectivity in frontal-striatal areas as compared to controls. Our results add further evidence for an altered reward processing in PG and underline the importance of loss avoidance processing. Moreover, our findings of volumetric alterations within and increased connectivity between PFC and reward system, suggest an altered interaction between these brain regions. Since such alterations in cortico-striatal circuits resemble those reported for substance-related addictions, our findings support the new classification of PG in the DSM-5.

No description available.

A polineuropatia inflamatória desmielinizante crônica (PIDC) é uma síndrome caracterizada fundamentalmente pela disfunção do Sistema Nervoso Periférico e que afeta muito a qualidade de vida dos pacientes. O envolvimento da PIDC com o Sistema Nervoso Central tem sido descrito, maiormente como sendo subclínico, porém não há estudos sobre a caracterização deste envolvimento de uma forma ampla e quantitativa. Avaliamos 11 pacientes com PIDC, todos tratados e sem sinais clínicos de alterações centrais, e 11 controles, pareados em gênero e faixa etária de 19 a 69 anos. Foram adquiridas neuroimagens em uma máquina de Ressonância Magnética de alto campo (3T) usando diferentes técnicas de imagens; volumétricas ponderadas em T1, volumétricas de inversão e recuperação com atenuação de fluidos e ponderadas em T2, relaxométricas de cinco ecos para mapas de T2, de transferência de magnetização e por tensor de difusão. As imagens foram processadas em diferentes ferramentas computacionais e foram obtidos resultados para estudos da difusibilidade, volumetria, morfometria, tratometria e conectividade cerebral, além de achados radiológicos para os pacientes. As análises de grupos foram executadas por; 1) testes paramétricos monocaudais de duas amostras pareadas para os resultados da volumetria, da tratometria e conectividade cerebral; 2) mapeamento estatístico paramétrico para os resultados da morfometria baseada em voxel e; 3) estatística espacial baseada em tratos para os resultados da difusibilidade. Foram detectas alterações em todas as comparações. Os principais achados indicam um envolvimento possivelmente caracterizado por uma perda volumétrica encefálica generalizada, sobretudo nas regiões periventriculares associadas a ventrículos proeminentes acrescido de, um aumento da difusibilidade transversa e oblíqua nos maiores tratos de substância branca e, também há uma perda de densidade na substância branca periventricular e um aumento na substância cinzenta em uma região que sinaliza para o espessamento trigeminal bilateral e, uma redução geral da conectividade cerebral estrutural. / Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a severe disease fundamentally characterized by dysfunction of the Peripheral Nervous System and affects greatly the quality of life of patients. The Central Nervous System (CNS) involvement in CIDP has not been described using recent quantitative neuroimaging techniques. We evaluated 11 patients with CIDP, all treated and without clinical signs of central alterations and 11 controls matched for gender and age group of 19 to 69 years. Magnetic Resonance Imaging were performed on a 3T scanner using different imaging techniques; structural 3D T1-weighted, fluid-attenuated inversion recovery, relaxometry with 5 echoes pulse sequence for T2 maps, magnetization transfer weighted and diffusion tensor imaging. The images were processed on different tools and were obtained results for the studies of diffusivity, volumetry, morphometry, tractometry, brain connectivity, and radiological findings of patients. Different statistical group analyses were performed in the quantitative results: 1) Parametric test for volumetry, tractometry and brain connectivity; 2) Parametric mapping for voxel morphometry; 3) Tract-based spatial statistics (TBSS) for diffusion coefficients. Changes were detected in all comparisons. In the patients, our main findings are: generalized loss brain volume more pronounced in periventricular regions associated with prominent ventricles, increased simultaneously perpendiculars and parallel diffusivity in the major tracts of the TBSS analyze, white matter density loss in the periventricular area, some bilateral trigeminal thickening, and general reduction of the brain connectivity. The CIDP affects the global brain and represents a demyelination in the CNS.

A polineuropatia inflamatória desmielinizante crônica (PIDC) é uma síndrome caracterizada fundamentalmente pela disfunção do Sistema Nervoso Periférico e que afeta muito a qualidade de vida dos pacientes. O envolvimento da PIDC com o Sistema Nervoso Central tem sido descrito, maiormente como sendo subclínico, porém não há estudos sobre a caracterização deste envolvimento de uma forma ampla e quantitativa. Avaliamos 11 pacientes com PIDC, todos tratados e sem sinais clínicos de alterações centrais, e 11 controles, pareados em gênero e faixa etária de 19 a 69 anos. Foram adquiridas neuroimagens em uma máquina de Ressonância Magnética de alto campo (3T) usando diferentes técnicas de imagens; volumétricas ponderadas em T1, volumétricas de inversão e recuperação com atenuação de fluidos e ponderadas em T2, relaxométricas de cinco ecos para mapas de T2, de transferência de magnetização e por tensor de difusão. As imagens foram processadas em diferentes ferramentas computacionais e foram obtidos resultados para estudos da difusibilidade, volumetria, morfometria, tratometria e conectividade cerebral, além de achados radiológicos para os pacientes. As análises de grupos foram executadas por; 1) testes paramétricos monocaudais de duas amostras pareadas para os resultados da volumetria, da tratometria e conectividade cerebral; 2) mapeamento estatístico paramétrico para os resultados da morfometria baseada em voxel e; 3) estatística espacial baseada em tratos para os resultados da difusibilidade. Foram detectas alterações em todas as comparações. Os principais achados indicam um envolvimento possivelmente caracterizado por uma perda volumétrica encefálica generalizada, sobretudo nas regiões periventriculares associadas a ventrículos proeminentes acrescido de, um aumento da difusibilidade transversa e oblíqua nos maiores tratos de substância branca e, também há uma perda de densidade na substância branca periventricular e um aumento na substância cinzenta em uma região que sinaliza para o espessamento trigeminal bilateral e, uma redução geral da conectividade cerebral estrutural. / Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is a severe disease fundamentally characterized by dysfunction of the Peripheral Nervous System and affects greatly the quality of life of patients. The Central Nervous System (CNS) involvement in CIDP has not been described using recent quantitative neuroimaging techniques. We evaluated 11 patients with CIDP, all treated and without clinical signs of central alterations and 11 controls matched for gender and age group of 19 to 69 years. Magnetic Resonance Imaging were performed on a 3T scanner using different imaging techniques; structural 3D T1-weighted, fluid-attenuated inversion recovery, relaxometry with 5 echoes pulse sequence for T2 maps, magnetization transfer weighted and diffusion tensor imaging. The images were processed on different tools and were obtained results for the studies of diffusivity, volumetry, morphometry, tractometry, brain connectivity, and radiological findings of patients. Different statistical group analyses were performed in the quantitative results: 1) Parametric test for volumetry, tractometry and brain connectivity; 2) Parametric mapping for voxel morphometry; 3) Tract-based spatial statistics (TBSS) for diffusion coefficients. Changes were detected in all comparisons. In the patients, our main findings are: generalized loss brain volume more pronounced in periventricular regions associated with prominent ventricles, increased simultaneously perpendiculars and parallel diffusivity in the major tracts of the TBSS analyze, white matter density loss in the periventricular area, some bilateral trigeminal thickening, and general reduction of the brain connectivity. The CIDP affects the global brain and represents a demyelination in the CNS.