Dissertations / Theses on the topic 'Gyrus du cingulum'

Outre le stress chronique, la douleur chronique représente une cause majeure de dépression. En effet, environ 50% des patients qui souffrent d’une douleur chronique développent des troubles de l’humeur. Les perturbations des structures cérébrales impliquées dans la perception de la douleur pourraient contribuer à cette comorbidité, dont les mécanismes restent pourtant mal compris. Nous avons étudié l’implication du cortex cingulaire antérieur (CCA) dans les conséquences sensorielles et émotionnelles de la douleur neuropathique dans un modèle murin. Nous avons montré qu’une lésion du CCA ou une inhibition des neurones pyramidaux du CCA préviennent l’émergence des désordres émotionnels dans notre modèle. De plus, nos résultats indiquent que ces conséquences émotionnelles coïncident avec une hyperactivité neuronale dans le CCA. En conclusion, nous montrons que le CCA est une structure clé pour la dépression induite par la douleur neuropathique
Besides chronic stress, chronic pain is one of the prevalent determinants for depression. Indeed, around 50% of chronic pain patients develop mood disorders. Alterations in brain regions implicated in pain processing may also be involved in affective processing, thus potentially be responsible of mood disorders. However, the underlying mechanisms of this comorbidity are not yet elucidated. Here, we studied the role of the anterior cingulate cortex (ACC) in the somatosensory, aversive and anxiodepressive consequences of neuropathic pain. We showed that a permanent lesion or temporal inhibition of ACC pyramidal neurons blocked the development or suppressed the expression of an anxiodepressive phenotype in neuropathic mice. In addition, anxiodepressive-like behavior coincided with ACC hyperactivity. In conclusion we show that the ACC is a critical hub for neuropathic pain-induced depression

La Maladie de Parkinson (MP) est une maladie neuro-dégénérative fréquente, caractérisée par une déplétion dopaminergique striatale. Elle s'accompagne précocement de troubles cognitifs, notamment attentionnels, dont l’origine reste imprécise. Deux hypothèses sont évoquées : un déficit du contrôle volontaire de l'attention vers la tâche en cours (processus de type « top-down » (TD)) ou un défaut d’inhibition des informations non pertinentes pour la tâche (par défaillance de processus de type « bottom-up » (BU)). Les processus attentionnels, souvent explorés par la mesure de variables comportementales, peuvent également bénéficier de l'enregistrement des composantes N200 et P300 des potentiels évoqués cognitifs (PEC). La P300 comprend deux sous-composantes : (1) la P3a, survenant préférentiellement après un distracteur, reflétant un traitement BU ; (2) la P3b, associée à la détection de cibles et reflétant un traitement TD. La N200 se décompose en une « no-go-N2 » antérieure, impliquée dans la détection de la déviance et les mécanismes d’inhibition et une « go-N2 » postérieure, engagée dans les processus de catégorisation des cibles. Dans la MP, ces composantes ont le plus souvent une latence allongée et une amplitude réduite. La modification des générateurs des PEC dans la MP n’a, à notre connaissance, jamais été explorée. L’objectif de cette thèse est de préciser les mécanismes sous-jacents aux troubles attentionnels dans la MP. En cas de dysfonctionnement TD, les réseaux impliqués dans la genèse de la P3b et/ou de la N200 postérieure pourraient être altérés. Si une dysfonction BU en est à l’origine, les générateurs de la P3a et/ou de la N200 antérieure devraient être modifiés. Nous avons enregistré en haute résolution les PEC de 15 sujets sains jeunes, au cours d’un paradigme « oddball » visuel à trois stimulus afin d’étudier les générateurs des PEC chez le sujet sain. Le même enregistrement a ensuite été effectué chez 15 sujets atteints d’une MP comparés à 15 sujets appariés. Les latences et amplitudes des composantes des PEC ont été comparées au moyen d’analyses de variance. L’exploration des générateurs des PEC a été effectuée pour chaque sujet et dans chaque condition au moyen d’une méthode distribuée d’analyse de source, swLORETA (standardized weighted low resolution tomography). Les analyses statistiques de groupes des générateurs de la P300 ont été effectuées au moyen du logiciel SPM, celles de la N200 au moyen de méthodes de permutations. Chez les sujets jeunes, le réseau fronto-pariétal dorsal (FPD) apparaît impliqué dans la genèse des deux composantes de la P300, le réseau fronto-pariétal ventral étant spécifique du traitement de la cible. L’étude des générateurs de la N200 a mis en évidence le rôle prépondérant du cortex cingulaire antérieur (CCA) en interaction avec les réseaux fronto-pariétaux, le precuneus et le cortex cingulaire postérieur. Dans la MP, il existait une réduction des sources de la P300 générée par le distracteur au niveau du cortex dorsolatéral préfrontal (DLPF) appartenant au réseau FPD, en lien avec une augmentation des fausses alarmes aux distracteurs chez les patients, en faveur d'une défaillance des processus BU dans la MP. Une diminution des sources de la N200 a également été constatée au niveau du cortex DLPF et du CCA, dans toutes les conditions. Ceci suggère un dysfonctionnement de ces deux régions dès le stade précoce des processus attentionnels, seul le fonctionnement du cortex DLPF restant altéré spécifiquement dans le traitement des distracteurs lors des étapes ultérieures de traitement de l’information. Ces anomalies résultent probablement du dérèglement des boucles baso-corticales reliant le striatum associatif au cortex DLPF et CCA. Ceci entrainerait une altération du contrôle cognitif et des processus BU responsable d’anomalies de détection de la déviance et d'inhibition des stimulus non pertinents, sous-jacentes aux troubles de l’attention sélective dans la MP
Parkinson’s disease (PD) is a frequent neurodegenerative disease which is responsible for striatal dopaminergic depletion. PD patients present an early cognitive impairment, particularly attentional disorders. The origin of this impairment is still debated. It could result from a reduced allocation of attentional resources to the ongoing task (“top-down” process (TD)) or a defective inhibition of irrelevant events (failure of “bottom-up” filtering process (BU). Investigation of attentional processes mostly rely on behavioral analysis, but the study of the N200 and P300 components of the cognitive event-related potentials (ERPs) may be of interest. P300 can be divided into two subcomponents: (1) P3a, which occurs preferentially after distracter stimuli and is associated with BU processes; (2) P3b, related to target detection and associated with TD mechanisms. The N200 also comprises two main components: an anterior “no-go-N2", involved in mismatch detection and inhibition mechanisms, and a posterior “go-N2”, related to target categorization processes. Most of previous studies in PD have shown a longer latency and reduced amplitude of N200 and P300. To the best of our knowledge, modulation of their generators in PD has never been investigated. The main aim of this work was to improve our knowledge of the mechanisms of attention disorders in PD. If the attentional impairment in PD results from a failure of TD processes, this would result in modifications of the networks underlying the P3b and/or the posterior N2 during target detection. Alternatively, if this disorder is consecutive to a failure of BU processes, this would lead to difficulty in resisting interference from distracter stimuli and would change the characteristics of the P3a and/or anterior N200. ERPs were recorded in 15 young healthy subjects with high resolution electroencephalography during a three stimuli oddball paradigm in order to localize N200 and P300 generators in healthy subjects. Then, they were recorded with the same procedure in 15 patients with PD and 15 matched healthy controls. Group comparisons of the ERPs latency and amplitude were performed with analyses of variance. Generators of the ERPs components were identified for each subject and in each condition with a distributed source localization method, swLORETA (standardized weighted low resolution tomography). Group analyses of swLORETA solutions were performed with SPM® for the P300 subcomponents and with a permutation method for the N200. In young healthy controls, we showed an involvement of the dorsal frontoparietal (DFP) network in both P3a and P3b generation, while the ventral frontoparietal network was specific to target processing. The anterior cingulate cortex (ACC) that interacts with the frontoparietal networks, had a preponderant role in N200 generation. Other areas, namely the precuneus and the posterior cingulate cortex, which are connected to the ACC, are specific generators of some of the N200 subcomponents. In PD, a reduction of distracter-elicited P300 generators was found in the dorsolateral prefrontal cortex (DLPF), which is part of the DFP network, accordingly with an increased commission rate for distracter stimuli. These results suggest a failure of BU processes in PD. A reduced number of N200 generators was also displayed in both DLPF and ACC whatever the stimulus. This suggests a dysfunction of both the DLPF and the ACC at an early stage of attentional processes in PD, while only distracter processing was later impaired, in relation with a DLPF dysfunction. These abnormalities probably result from disturbances of the basocortical loops that link the associative striatum to the DLPF and ACC. This would then produce a sustainable alteration of cognitive control and BU processes, responsible for abnormal mismatch detection and inhibition of irrelevant stimuli, which would underlie the selective attention impairment in PD

Le cortex cingulaire antérieur (CCA) est une région préfrontale située au centre d’un réseau permettant l’échange d’informations cognitives, motrices, limbiques et viscérales, la plaçant ainsi comme un sujet incontournable dans l’étude de pathologies complexes telles que les troubles anxio-dépressifs. Afin de pouvoir aborder ces pathologies chez la souris, nous avons établi par traçage neuronal le connectome complet des différentes aires composant le CCA. Nous avons ainsi montré qu’une grande majorité des structures de ce connectome communique de manière réciproque avec cette région et que, selon les aires cingulaires, des spécificités de densité d'innervation et de topographie peuvent exister. Ceci suggère des fonctions partagées mais également des rôles plus spécifiques à chaque aire. A partir de ce connectome, nous avons ensuite montré, par une approche optogénétique associée à des tests comportementaux, que l'activation répétée de la projection de l’amygdale au CCA est susceptible d'induire des comportements de type anxio-dépressif chez des souris naïves. Ce travail met donc en évidence le rôle d'une partie du connectome du CCA dans l'établissement des troubles de l'humeur
The anterior cingulate cortex (ACC) is a prefrontal region located at the center of a network allowing the sharing of cognitive, motor, limbic and visceral information, placing it as an interesting target for the study of complex pathologies like mood disorders. To investigate these diseases in mice, we provided the complete connectome of each ACC areas by a tract-tracing approach. We demonstrated that the majority of structures constituting this connectome are reciprocally connected with the ACC and that some density and topographical connection specificities were observed among cingulate areas. These results potentially suggest some shared functions between cingulate areas, also completed by specific roles inherent to each area. Using this connectome, we demonstrated that the repeated activation of the amygdala projection to the ACC was able to induce anxiodepressive-like behaviors in naïve mice, by using optogenetics combined with behavioral tests. This study highlights for the first time the implication of a portion of the ACC connectome in the establishment of mood disorders

Abnormal connectivity of the intrinsic anticorrelated networks, the task-negative network (TNN) and task-positive network (TPN), is implicated in schizophrenia. Comparisons between schizophrenic patients and their unaffected siblings offer an opportunity to further understand illness susceptibility and pathophysiology. We hypothesized that schizophrenic patients would demonstrate hyperconnectivity in the intrinsic networks and that similar, but less pronounced, hyperconnectivity would be evident in the networks of the unaffected siblings. Resting-state functional magnetic resonance images were obtained from schizophrenic patients (n=25), their unaffected siblings (n=25), and healthy controls (n=25). The posterior cingulate cortex/precuneus (PCC/PCu) and right dorsolateral prefrontal cortex (DLPFC) were used as seed regions to identify the TNN and TPN. Interregional connectivity strengths were analyzed using overlapped intrinsic networks composed of regions common to the intrinsic networks of the three subject groups. In the TNN, schizophrenic patients alone demonstrated hyperconnectivity between the PCC/PCu and left inferior temporal gyrus and between the ventral medial prefrontal cortex and the right lateral parietal cortex. Both schizophrenic patients and their unaffected siblings showed increased connectivity in the TNN between the bilateral inferior temporal gyri. In the TPN, schizophrenic patients showed hyperconnectivity between the left DLPFC and right inferior frontal gyrus relative to unaffected siblings, though this trend only approached statistical significance in comparison to healthy controls. Resting-state hyperconnectivity of the intrinsic networks may underlie the pathophysiology of schizophrenia by disrupting network coordination. Similar, though milder, hyperconnectivity in unaffected siblings of schizophrenic patients may contribute to their cognitive deficits and increased risk to develop schizophrenia.

Representing a major public health concern, suicide is a leading cause of death worldwide. Generally regarded as a behavior with a multitude of state and trait dependent risk factors (e.g. psychiatric disorders, substance abuse, genetics), explanations as to why certain individuals commit suicide while others do not are complex. Of interest is in studying potential trait dependent variables involved in the neurobiology of suicide, particularly at the cellular level. Knowledge of the cellular integrity may aid in explaining the observed macroscopic alterations and ultimately the behavioral correlates associated with suicidality. Therefore we set out to summarize extant knowledge of the cellular alterations occurring in the brains of major depressive and suicide individuals. Following this, we conducted our own cellular investigation in a region known to be altered in major depression and suicide, a supracallosal area of BA24a. Neuronal and glial cell densities as well as neuronal cell sizes were assessed in upper and lower cortical layers between sudden-death controls and MDD suicide subjects. Secondary analyses were also conducted to examine the effect of alcohol on depressed suicides. Analyses of cell densities and neuronal soma sizes between controls and MDD suicide subjects did not reveal any significant differences. Further analyses showed increased glial cell densities in alcoholic depressed suicides. Future studies are necessary to examine explicit changes in the cellular compositions occurring in alcoholic dependent individuals. Staining techniques aimed at targeting specific subtypes of neurons and glial cells will help determine if these cell populations do in fact have an influential role in suicide and MDD.

Foi realizada a comparação entre os achados de espectroscopia de prótons por ressonância magnética utilizando a sequência PRESS (point resolved spectroscopy), com TE curto (35ms) no cíngulo posterior e hipocampos de 29 pacientes com doença de Alzheimer (leve e moderada) e 15 controles. As relações de metabólitos com melhor sensibilidade e especificidade na diferenciação entre os grupos foram em ordem decrescente: Naa/Cr do cíngulo, mI/Naa do cíngulo, mI/Naa dos hipocampos e mI/Cr dos hipocampos. Não houve vantagens, nesta casuística, na realização da espectroscopia de prótons nos hipocampos, um local tecnicamente mais difícil e demorado em relação ao cíngulo posterior. Observou-se correlação positiva da relação Naa/Cr e negativa da relação mI/Naa do cíngulo posterior com o MMSE
The objective of this study is to compare the findings on Magnetic Resonance Spectroscopy using PRESS (point resolved spectroscopy) technique with short TE (35ms) in the posterior cingulate and hippocampi of 29 patients with Alzheimer's disease (mild and moderate) and 15 controls. The metabolic ratios with highest sensitivity and specificity were (in a decreasing order): posterior cingulate Naa/Cr, posterior cingulate mI/Naa, hippocampi mI/Naa and hippocampi mI/Cr. In the group analised it seems there is no advantage in performing MRS in the hippocampi instead of posterior cingulate, a technically challenging location, usually leading to a longer examination time. In the posterior cingulate we observed a positive correlation with Naa/Cr ratio and a negative correlation with mI/Naa ratio and the MMSE

INTRODUÇÃO: O teste de fluência verbal fonológica é uma tarefa neuropsicológica amplamente utilizada em estudos de neuroimagem funcional que analisam os circuitos neurais relevantes para a produção de linguagem. A maioria dos estudos que utilizam a RMf para analisar as áreas cerebrais de maior ativação durante a tarefa de fluência verbal é realizado na língua inglesa. Embora estudos anteriores tenham demonstrado que dependendo da língua falada possa ocorrer diferença de desempenho na tarefa de fluência verbal, ainda não está claro se esta diferença leva a mudanças do padrão de ativação cerebral. Há indícios na literatura que a ativação cerebral regional durante a tarefa de fluência verbal pode variar com o aumento de dificuldade da tarefa, sendo o cíngulo anterior a área cerebral que parece estar envolvida no processo de adaptação ao grau de dificuldade da tarefa. Estudos com sujeitos saudáveis demonstram também a influência de variáveis demográficas, como idade, escolaridade, gênero e classificação socioeconômica no desempenho na produção de palavras, com alguns estudos reportando maior ativação cortical nos homens em comparação às mulheres. OBJETIVOS: Avaliar os efeitos da variação do grau de dificuldade da tarefa de fluência verbal utilizando a técnica de ressonância magnética funcional. Analisar se há correlação entre os dados demográficos e o desempenho na tarefa de fluência verbal. Comparar o padrão de ativação cerebral entre os gêneros. MÉTODOS: Foram incluídos 21 voluntários saudáveis (12 homens), destros e falantes do português do Brasil como primeira língua. Foram colhidos dados sociodemográficos, neuropsicológicos e de desempenho dos voluntários. Comparamos os achados adquiridos através da técnica de ressonância magnética funcional durante a produção de palavras iniciadas com letras classificadas anteriormente como fáceis e difíceis para produzir palavras na língua portuguesa. As imagens foram adquiridas em aparelho de ressonância magnética de 1,5 T através de uma sequência de aquisição de imagens compressed epi que permite aos sujeitos produzirem as palavras apenas durante o período de silêncio do equipamento. As imagens foram analisadas através do software XBAM para os grupos e para a análise de correlação comportamental. RESULTADOS: A tarefa de fluência verbal engajou circuitos cerebrais incluindo córtex frontal medial e inferior esquerdo, putamen e tálamo (p<0,001). O aumento de dificuldade da tarefa de fluência verbal fonológica na língua portuguesa mostrou-se associado a uma diferença significativa de ativação apenas em uma região cerebral, o cerebelo (maior ativação durante a tarefa realizada com letras mais fáceis). Houve correlações significativas entre o desempenho na tarefa de fluência verbal fonológica na língua portuguesa e o grau de ativação do cíngulo anterior quando foram usadas letras difíceis para produção de palavras, mas não com letras fáceis. Não houve correlação significativa entre os dados demográficos (idade, escolaridade, gênero e classificação socioeconômica) e o desempenho durante a produção de palavras iniciadas com letras fáceis e com letras difíceis. Observamos maior ativação de cíngulo posterior e giro lingual nas mulheres em comparação aos homens durante a produção de palavras iniciadas com letras difíceis e interação positiva entre os gêneros e os graus de dificuldade na região de cíngulo anterior, demonstrando maior ativação do cíngulo anterior nos homens durante a produção de palavras iniciadas com letras difíceis. CONCLUSÃO: Apesar das diferenças lingüísticas, o padrão de ativação cerebral encontrado no nosso estudo foi consistente com o padrão verificado em outras línguas, com recrutamento de múltiplas áreas cerebrais durante a produção de palavras. Na língua portuguesa, assim como na língua inglesa, há indícios de que o aumento de dificuldade da tarefa está associado com maior engajamento de cíngulo anterior. Houve diferenças entre os gêneros em termos do engajamento de áreas cerebrais consideradas críticas para o desempenho na tarefa de fluência verbal fonológica, particularmente no cíngulo anterior
INTRODUCTION: Phonological verbal fluency is a neuropsychological test used in numerous functional neuroimaging studies to allow the assessment of the neural circuits relevant to language production. The majority of studies that use functional magnetic resonance imaging (fMRI) to analyze the cerebral areas with greater activation during the verbal fluency task have been carried out in English. Although there is evidence that the verbal fluency performance varies as a function of the spoken language, it is unclear if this difference is associated with differences in cerebral activation patterns. Added to that, there is neuroimaging evidence that patterns of regional cerebral activation during VF task may vary with task demand. In particular, the anterior cingulate cortex seems critical to the adaptation process to the level of difficult. Studies of healthy individuals have demonstrated the influence of demographic variables, such as age, level of education, gender and socio-economic status, on word production performance, and some authors have shown greater cortical activation in men than in women. OBJECTIVES: To use the fMRI technique to evaluate the effect of varying levels of difficult of verbal fluency task on the brain activation patterns in healthy subjects. To analyze whether there is a significant correlation between demographic variables and verbal fluency performance. To compare cerebral activation patterns between genders. METHODS: We recruited 21 (12 men) right-handed healthy volunteers, having Portuguese as their first language. Demographic, neuropsychological and behavioral data were collected. We compared fMRI data acquired during production of words beginning with letters classified as easy or hard for word production in Portuguese. Images were acquired in 1,5 T magnet through a clustered image acquisition sequence that allowed overt verbal responses to be made in the absence of scanner noise. Data were analyzed through XBAM software on group basis and for behavioral correlation. RESULTS: The phonological verbal fluency task engaged a network including the left inferior and middle frontal cortices, putamen and thalamus (p<0.001). The hard condition was associated with greater anterior cingulate activation than the easy condition when associated with the performance, as previously demonstrated in studies carried out with English speaking subjects. Increased phonological verbal fluency task demand in Portuguese was associated with activation differences in only one brain region, namely the cerebellum (in the direction of greater activation during performance of the task with easy letters). There were significant correlations between phonological verbal fluency task performance in Portuguese and the intensity of anterior cingulate activation, when hard letters to produce words were used (but not with easy letters). There were no significant correlations between demographic variables and the performance during production of words beginning with easy or difficult letters. There was greater activation of the posterior cingulate cortex during the production of words beginning with the difficult letters in women than in men. There was also a significantly positive interaction between gender and level of difficult in anterior cingulate cortex, with men showing greater activation of this brain region during the word production beginning with difficult letters relative to women. CONCLUSIONS: Despite grammatical differences, the patterns of cortical activations observed in our study were in accordance with fMRI studies of phonological verbal fluency task carried out in other languages, with recruitment of a set of distributed cerebral areas during the word production. There is evidence that increased task demand is associated with greater engagement of the anterior cingulate cortex in Portuguese, similarly to the patterns previously observed in English. There were gender differences in regard to the engagement of brain regions seen as critical to verbal fluency performance, particularly in the anterior cingulate cortex

Background: Patients with Panic Disorder (PD) direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD. Methods: A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry) as well as artificial odors (peach, artificial sweat) as non-fearful non-body odors. Principal Findings: The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology. Conclusions: The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear-network which is associated with an increased severity of the psychopathology.

Background: Patients with Panic Disorder (PD) direct their attention towards potential threat, followed by panic attacks, and increased sweat production. Onés own anxiety sweat odor influences the attentional focus, and discrimination of threat or non-threat. Since olfactory projection areas overlap with neuronal areas of a panic-specific fear network, the present study investigated the neuronal processing of odors in general and of stress-related sweat odors in particular in patients with PD. Methods: A sample of 13 patients with PD with/ without agoraphobia and 13 age- and gender-matched healthy controls underwent an fMRI investigation during olfactory stimulation with their stress-related sweat odors (TSST, ergometry) as well as artificial odors (peach, artificial sweat) as non-fearful non-body odors. Principal Findings: The two groups did not differ with respect to their olfactory identification ability. Independent of the kind of odor, the patients with PD showed activations in fronto-cortical areas in contrast to the healthy controls who showed activations in olfaction-related areas such as the amygdalae and the hippocampus. For artificial odors, the patients with PD showed a decreased neuronal activation of the thalamus, the posterior cingulate cortex and the anterior cingulate cortex. Under the presentation of sweat odor caused by ergometric exercise, the patients with PD showed an increased activation in the superior temporal gyrus, the supramarginal gyrus, and the cingulate cortex which was positively correlated with the severity of the psychopathology. For the sweat odor from the anxiety condition, the patients with PD showed an increased activation in the gyrus frontalis inferior, which was positively correlated with the severity of the psychopathology. Conclusions: The results suggest altered neuronal processing of olfactory stimuli in PD. Both artificial odors and stress-related body odors activate specific parts of a fear-network which is associated with an increased severity of the psychopathology.

Hintergrund und Ziel der Untersuchung: Patienten mit schizophrenen Erkrankungen zeigen in einer Vielzahl von Untersuchungssituationen eine verminderte Funktion frontaler Hirnregionen (Hypofrontalität), die insbesondere auch den anterioren cingulären Cortex (ACC) betrifft. Verschiedene Arten antipsychotischer Medikation unterscheiden sich hinsichtlich ihrer Wirkung auf Metabolismus und Funktion des Frontalcortex, wobei es Hinweise darauf gibt, dass atypische Antipsychotika diesen Bereich des Gehirns positiv beeinflussen, während konventionelle Antipsychotika (Typika) hier nur geringe oder sogar negative Effekte zeigen. Hinsichtlich der Auswahl eines Antipsychotikums zu Beginn einer medikamentösen Behandlung gibt es bislang keine etablierten neurophysiologischen/biologischen Marker, die eine Vorhersage der Therapie-Response unter verschiedenen Arten antipsychotischer Medikation erlauben. Ziel der Studie war es daher, die Eignung der NoGo-Anteriorisierung (NGA) als Prädiktor der Therapie-Response schizophrener Patienten unter typischer bzw. atypischer Medikation zu untersuchen. Die NGA ist ein neurophysiologischer Marker, der die Funktion präfrontaler Areale einschließlich des ACC widerspiegeln soll. Unter Zuhilfenahme dieses Parameters wurde an einer Gruppe schizophrener Patienten überprüft, ob das Ausmaß der initialen Hypofrontalität eine Vorhersage der individuellen Therapie-Response erlaubt. Methoden: Es wurden 76 Patienten mit Erkrankungen aus dem schizophrenen Formenkreis zu jeweils drei Messzeitpunkten neurophysiologisch, neuropsychologisch und psychometrisch getestet. Die Baseline-Messung (t1) fand innerhalb der ersten drei Tage eines stationär-psychiatrischen Aufenthalts, die beiden Folgemessungen (t2, t3) drei bzw. sechs Wochen nach Beginn einer Therapie mit typischen (n=36) oder atypischen Antipsychotika (n=40) statt. Im Rahmen der neurophysiologischen Untersuchung führten die Patienten eine Go-NoGo-Aufgabe durch, wobei anhand der durch Go- und NoGo-Stimuli evozierten ereigniskorrelierten Potentiale individuell die NGA ermittelt wurde. Beide Behandlungsgruppen wurden aufgrund der NGA-Werte zu t1 in Patienten mit initial starker vs. schwacher Frontalhirnfunktion unterteilt (Mediansplit). Ergebnisse: Alle Patientengruppen zeigten eine signifikante Besserung der psychotischen Symptomatik im Verlauf des 6-wöchigen Untersuchungszeitraums. Außerdem hatten Atypika hypothesengemäß einen signifikant positiven Einfluss auf die Entwicklung der neuropsychologischen Testleistungen, während Typika oftmals mit einer Verschlechterung entsprechender Maße einhergingen. Atypika hatten zudem eine günstigere Wirkung auf die subjektiv erlebte Lebensqualität der Patienten. Darüber hinaus war die zu t1 erhobene NGA ein signifikanter Prädiktor der Therapie-Response. Niedrige Werte der NGA zu Beginn der Behandlung sagten dabei ein besonders gutes Ansprechen auf atypische Antipsychotika voraus, während hohe Werte der NGA zu t1 mit einer besonders deutlichen klinischen Besserung unter typischer Medikation einhergingen. Die NGA korrelierte zudem signifikant mit den neuropsychologischen Testleistungen, unterlag selbst aber keinen systematischen Veränderungen unter typischer vs. atypischer Medikation. Schlussfolgerung: Der auf der Basis früherer Untersuchungen vermutete Zusammenhang zwischen der NGA und präfrontalen Hirnfunktionen konnte anhand der vorliegenden Befunde bestätigt werden. Außerdem war aufgrund der zu Beginn einer stationär-psychiatrischen Behandlung gemessenen NGA eine signifikante Vorhersage der Therapie-Response unter typischen und atypischen Antipsychotika möglich. Die NGA könnte somit im klinischen Alltag zu einer individualisierten Entscheidungsfindung bei der Auswahl eines antipsychotischen Präparats, unter Berücksichtigung pathophysiologischer Aspekte der Erkrankung, beitragen
Background and objective: Schizophrenic patients often exhibit functional deficits in frontal cortical areas (hypofrontality), particularly within the anterior cingulate cortex (ACC). Different classes of antipsychotic medication differ with respect to their influence on function and metabolism of the frontal cortex, with a more positive effect of atypical as compared to typical compounds. Regarding the therapeutic choice of a particular antipsychotic substance, previous research efforts have not yet been able to establish neurobiological markers that are able to predict the patients’ clinical response to different kinds of antipsychotic medication. The present study, therefore, aimed at examining the NoGo-Anteriorization (NGA) as a possible predictor of the clinical response to typical and atypical antipsychotic treatment. The NGA is a neurophysiological marker that presumably reflects activation of prefrontal cortical structures, including the ACC. For the present study, a group of schizophrenic patients was examined three times in the course of a psychiatric in-patient treatment, to confirm that prefrontal cortical function is positively influenced by atypical antipsychotics, and to explore whether the amount of hypofrontality at the beginning of treatment (quantified by means of the NGA) allows for a prediction of the clinical response to both kinds of antipsychotic medication. Methods: 76 patients with schizophrenic illnesses were examined three times each, by means of neurophysiological, neuropsychological and psychometric measures. Baseline measurements (t1) were conducted within the first three days of a psychiatric in-patient treatment, follow-up measurements (t2, t3) three and six weeks after the start of a therapy with typical (n=36) or atypical antipsychotics (n=40). For the neurophysiological examination, patients performed a Go-NoGo-task, and the individual NGA was calculated on the basis of the corresponding Go- and NoGo-ERPs (event-related potentials). Moreover, the NGA at baseline was used to subdivide both treatment groups into patients with initially strong vs. weak frontal cortical function (NGA above and below group-median, respectively). Results: On a clinical level, patients in each of the four study groups improved significantly over the course of the study period. In line with previous findings, atypical antipsychotics furthermore positively influenced neuropsychological test performance, whereas typical medication often caused a decline in test scores. Similarly, atypical compounds had a more favourable impact on the patients’ self-reported quality of life. Moreover, baseline values of the NGA significantly predicted the patients’ clinical response: Low values at t1 were associated with a particularly strong improvement under atypical medication, whereas high initial values of the NGA predicted a particularly good response to typical antipsychotics. The NGA furthermore significantly correlated with neuropsychological test scores, but did not systematically change over the course of a treatment with typical vs. atypical antipsychotics. Conclusion: The present findings confirm the putative association between the NGA and prefrontal brain functions. Furthermore, the NGA at the beginning of a psychiatric in-patient treatment significantly predicted the clinical response to typical and atypical antipsychotic treatment. Since the NGA can be easily determined in clinical routine settings, it might be a useful parameter for the development of individualised treatment strategies based on pathophysiological aspects of schizophrenic illnesses

Conclusion: The results suggest that ASD children have deficits in attentional and inhibitory control. Frontal dysfunction and weak ACC engagement in ASD were supported as the underlying neuronal inefficiency.
Methods: 20 children with high-functioning ASD [Mean Age (SD): 10.75 years old (2.07 years); Mean IQ (SD): 101.4 (16.8)] and age- and IQ-matched normal children (NC) [Mean Age (SD): 9.80 years old (1.88 years); Mean IQ (SD): 110.7(17.8)] were investigated electrophysiologically during performance of a visual Go/NoGo task. An electrophysiological source localization method was employed to further analyze the data. Several different neurospsychological tests were also performed to provide behavioral measures on attention and inhibition.
Objectives: To investigate neurophysiologic abnormalities in frontal and anterior cingulate cortex underlying attentional and inhibitory control in children with Autism Spectrum Disorder (ASD).
Results: ASD children showed a significantly task-related lower frontal theta activity. This effect was associated with a significantly reduced activation of the anterior cingulate cortex (ACC). Both groups also differ significantly regarding the behavioral aspects of attention and inhibition.
Leung, Shuk Yin Connie.
"November 2009."
Adviser: Chan Sue-Yin Agnes.
Source: Dissertation Abstracts International, Volume: 72-01, Section: B, page: .
Thesis (Ph.D.)--Chinese University of Hong Kong, 2010.
Includes bibliographical references (leaves 65-85).
Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web.
Abstracts also in Chinese.

Die neonatale Hypoxie, als Schwangerschafts- und Geburtskomplikation, ist der wichtigste prädisponierende Umweltfaktor in der Pathophysiologie der Schizophrenie. Sie führt zu einer Schädigung des Gehirns und einer Störung der Hirnentwicklung. Insgesamt sind die neurobiologischen Auswirkungen, insbesondere auf die Zellproliferation, unklar. Im Tiermodell konnten bereits Verhaltensauffälligkeiten ähnlich der Schizophrenie, infolge chronischer neonataler Hypoxie, festgestellt werden. Störungen in der Zellentwicklung könnten hierfür die Ursache sein. Die Hypothese, dass der Beginn der abnormalen Hirnentwicklung perinatal liegt, während erste klinische Symptome im frühen Erwachsenenalter manifest werden, unterstützt diese Ergebnisse. Die Hirnentwicklung der Ratte ist in der frühen postnatalen Periode vergleichbar mit der eines menschlichen Fötus im dritten Trimenon der Schwangerschaft und eignet sich daher pathologische Prozesse im zentralen Nervensystem des Menschen zu reflektieren. In der vorliegenden Arbeit wurde mit Hilfe postnataler Hypoxie die neuronale Zellproliferation in 20 männlichen Wistar-Ratten zu unterschiedlichen Zeitpunkten (postnataler Tag 13 und 39) untersucht. Die Hypoxietiere wurden vom postnatalen Tag vier bis acht einer Hypoxie, bestehend aus 11% O2 und 89% N2, ausgesetzt. Mit Hilfe der Bromodeoxyuridin-Peroxidasefärbung wurde die Zellproliferation in Hypoxie-vulnerablen Hirnregionen untersucht. Hierzu gehören der Gyrus cinguli, das Striatum, der Gyrus dentatus und die subventrikuläre Zone. Als Vergleich diente eine unbehandelte Kontrollgruppe. Durch ein Mikroskop mit Schrittmotorsystem und Stereo Investigator Software (MicroBrightField, UK) und der Optical Fractionator-Methode konnte erstmals festgestellt werden, dass Hypoxie-behandelte Tiere eine um 20% erhöhte Zellproliferation im Gyrus cinguli am postnatalen Tag 13 aufwiesen. Des Weiteren zeigte sich bei den Hypoxie-behandelten Tieren ein um 16% reduziertes Volumen im Striatum am postnatalen Tag 13. Am postnatalen Tag 39 zeigten sich keine signifikanten Unterschiede mehr. Diese Ergebnisse zeigen, dass ein vorübergehender Einfluss chronischer Hypoxie auf die Zellproliferation und das Volumen angenommen werden kann und das das Gehirn innerhalb gewisser Grenzen während der neuronalen Entwicklung tolerant gegenüber exogenen Noxen wie Hypoxie zu sein scheint. Die Ergebnisse bestätigen auch, dass nur ein kleiner Teil der Hypoxie-assoziierten Geburtskomplikationen zu einer Schizophrenie führt und der Erkrankung eine multifaktorielle Gen-Umwelt-Interaktion zugrunde liegt. Zukünftig könnte es, mit der besseren Kenntnis neurobiologischer Auswirkungen von Umweltfaktoren und genetischen Faktoren im Gehirn, möglich werden die Schizophrenie frühzeitiger zu erkennen und zu behandeln sowie behindernde Symptome zu reduzieren.