A esquizofrenia continua sendo um dos transtornos mais desafiadores para a clínica psiquiátrica, apesar dos estudos atuais que tentam elucidar sua fisiopatologia e buscar novas opções de tratamento. A n-acetilcisteína (NAC) é uma droga utilizada há mais de 30 anos na clínica médica no tratamento da intoxicação por acetaminofeno e como mucolítico na DPOC, entre outros. Evidências recentes apoiam o seu uso no tratamento de diversos transtornos neuropsiquiátricos, como depressão, transtorno afetivo bipolar, dependência química e esquizofrenia. A droga tem como provável mecanismo de ação um aumento na atividade antioxidante através do aumento nos níveis de glutationa (GSH) e modulação da neurotransmissão glutamatérgica. Nas duas últimas décadas, o estudo dos mecanismos neurobiológicos subjacentes aos transtornos psiquiátricos, bem como a investigação dos possíveis mecanismos e regiões cerebrais influenciados por substâncias psicofarmacológicas, recebeu importante contribuição das técnicas de neuroimagem funcional. Apesar disto, até o momento existem poucos estudos que avaliaram os mecanismos centrais relacionados às propriedades antipsicóticas da NAC em humanos. Este estudo tem o objetivo de investigar os efeitos da NAC em indivíduos portadores de esquizofrenia refratária em uso exclusivo de clozapina através de medidas de sintomas positivos e negativos e da avaliação da perfusão cerebral através de ressonância magnética nuclear utilizando a técnica de arterial spin labeling (ASL). Foram avaliados 20 sujeitos com esquizofrenia refratária em uso de clozapina em um estudo com distribuição aleatória, duplo-cego e controlado por placebo, utilizando a dose de 2000mg por dia de NAC. Do total da amostra, 14 tiveram as imagens perfusão sanguínea cerebral analisadas. O estudo teve a duração de oito semanas, com avaliações a cada quatro semanas e realização das RMN no início e ao final do período. Não foram observadas diferenças estatisticamente significativas entre os grupos placebo e NAC nas escalas BPRS e PANSS-N. O grupo que recebeuNAC apresentou mais efeitos colaterais, porém no geral a medicação foi bem tolerada. Também não se observou diferenças no FSC das diversas ROI analisadas. A NAC não produziu mudanças estatisticamente significativas nas escalas de sintomas e no FSC nesta amostra, apesar de outros estudos mostrarem diferenças significativas favorecendo a NAC. O presente estudo não mostrou melhora do FSC, mesmo após oito semanas, o que pode significar que a ASL pode não ser um método adequado para avaliar os efeitos cerebrais desta droga / Schizophrenia continues to be one of the most challenging psychiatric disorders in the clinical practice, despite recent studies that attempt to elucidate its pathophysiology and search for new treatment options. N-acetylcysteine (NAC) is a drug that has been used for more than 30 years in clinical medicine, in situations like acetaminophen intoxication and as mucolytic in COPD, among others. Recent studies support its therapeutic use in neuropsychiatric disorders such as depression, bipolar disorder, substance abuse and schizophrenia. The mechanism of action of NAC seems to occur in antioxidant activity, through the increase of glutathione levels (GSH) and in the modulation of glutamatergic neurotransmission. In the last two decades, the study of the neurobiological mechanisms underlying psychiatric disorders, as well as the investigation of the possible mechanisms and brain areas influenced by psychopharmacological substances received a significant contribution of functional neuroimaging techniques. Despite this, there are few studies that have evaluated the central mechanisms related to the antipsychotic properties of NAC in humans. This study aims to investigate the effects of NAC in subjects with refractory schizophrenia, exclusively on clozapine use, through measure of positive and negative symptoms and the evaluation of cerebral perfusion by magnetic resonance imaging, using the arterial spin labeling technique (ASL) . Twenty subjects with refractory schizophrenia were evaluated in a randomized, double-blind, placebo-controlled study using a dose of 2000mg per day of NAC. From the total sample, 14 had cerebral perfusion images analyzed. The study had a duration of eight weeks, with evaluations at each four weeks and MRI sessions before the beginning of NAC and at the end of the period. The results did not show statistically significant differences between placebo and NAC groups onthe BPRS and PANSS-N scales. The NAC group presented more side effects, although the medication was well tolerated in general. There were also no differences in the cerebral blood flow (CBF) among the regions of interest analyzed. Although there was no difference regarding symptoms scales the CBF in this sample, other studies found differences favoring NAC. The present study did not show changes of the CBF, which might mean that ASL is not an adequate technic to evaluate neurochemical effects of this drug

The brain; complex system people want to know about but still they are at the beginning of understanding it. There has been a lot of neuroimaging systems since developement of modern technologies and magnetic resonance imaging is one of them. In last days it isn't enough to examine only structural character of brain, the scientists are dealing with functional states more and more; the functional magnetic resonance imaging is perfectly good tool for this. There is a big amount of researches concerning individual brain regions but also a lot of them dealing with communication across the brain to clear up the causes of human behavior and functional failures. This thesis introduces the brain connectivity exploration, it uses the parcellation by anatomical atlases and it tries to use the knowledge of graph theory as one of the options to determine relations between brain centres and regions. The thesis introduces the software created for extraction of connectivity matrix resulting in graph processing and visualization.

Master’s thesis is aimed at familiarization with the principles of measurement and data processing functional magnetic resonance, focusing on the analysis of effective connectivity using dynamic causal modelling (DCM). The practical part includes three main thematic areas relating to the description of the processing and evaluation of measured or simulated data. First, there is on sample dataset described the neuroscientific SPM toolbox to analyze measured data. Then follows introduction of the proposed approach with which is investigated the behavior of the model estimation neural interactions with respect to the change of input parameters. This phenomenon is also simulated and on base of achieved results is recommended optimal approach to analyzing effective connectivity using dynamic causal modeling for the group of subjects. The last circuit in the practical part is assessment of shift the coordinates of brain areas on dynamic causal modelling results for the group of subjects from the data obtained from real measurements. Obtained results from simulated data and the results obtained from measured data are evaluated and discussed in the final part.

Die funktionelle Magnetresonanztomographie (fMRT) mit einer Feldstärke von 3 T ist in der prächirurgischen Nutzen-Risiko-Evaluation von Patienten mit Hirntumoren in bzw. im Bereich funktionell bedeutsamer Regionen, wie beispielsweise in Nachbarschaft zum Sulcus centralis, gut etabliert. Das Konzept der Neuroplastizität umfasst unter anderem Mechanismen zur zerebralen kortikalen Reorganisation nach Hirnschädigung. Ziel der vorliegenden prospektiven fMRT-Verlaufsstudie ist die Evaluation der noch wenig bekannten längerfristigen funktionellen Veränderungen des Gehirns nach neurochirurgischer Intervention. Zu diesem Zwecke wurden 14 Patienten mit Hirntumoren innerhalb oder in der Nähe des primären motorischen Cortex (MI) in die Studie eingeschlossen, welche sich einer neurochirurgischen Behandlung unterzogen. Bei 12 der Patienten wurde sowohl prä- als auch postoperativ eine funktionelle Bildgebung (fMRT) anhand des motorischen Paradigmas des unimanuellen und bimanuellen Fingertappens in einem 3 T MRT-Scanner durchgeführt. Wegen Bewegungsartefakten konnten lediglich 9 der Patienten in die weitere Auswertung eingeschlossen werden. Als Kontrollgruppe diente eine einmalige Untersuchung von neun gesunden Probanden. An längerfristigen Reorganisationsmustern konnten bei Patienten ohne Handparese sowohl die Rekrutierung der geschädigten als auch der intakten Hemisphäre des kortikalen motorischen Netzwerkes aufgezeigt werden. Tumorwachstum im Bereich des supplementär-motorischen Areals (SMA) ging mit einer bilateralen Rekrutierung der rostralen Portion des SMA (SMAr) einher. Die postoperative Reorganisation des motorischen Netzwerkes umfasste unter kontraläsionalen Fingertappen eine Lateralisierung der Aktivierung der SMAr zur nicht betroffenen Hemisphäre. Diese war umso ausgeprägter je größer das Tumorvolumen oder je näher der Tumor zur SMAr gelegen war. Demnach kann eine Dysfunktion der ipsilateralen SMAr präoperativ durch eine bilaterale und postoperativ durch eine kontraläsionale Rekrutierung kompensiert werden.

Background: Serotonin has been implicated in impulsive behaviours such as temporal discounting. While animal studies and theoretical approaches suggest that reduced tonic serotonin levels increase temporal discounting rates and vice versa, evidence from human studies is scarce and inconclusive. Furthermore, an important modulator of serotonin signalling, a genetic variation in the promoter region of the serotonin transporter gene (5-HTTLPR), has not been investigated for temporal discounting so far. Objective: First, the purpose of this study was to test for a significant association between 5-HTTLPR and temporal discounting. Second, we wished to investigate the effect of high/low tonic serotonin levels on intertemporal choice and blood oxygen-level-dependent response, controlling for 5-HTTLPR. Methods: We tested the association of 5-HTTLPR with temporal discounting rates using an intertemporal choice task in 611 individuals. We then manipulated tonic serotonin levels with acute tryptophan interventions (depletion, loading, balanced) in a subsample of 45 short (S)-allele and 45 long (L)/L-allele carriers in a randomised double-blind crossover design using functional magnetic resonance imaging and an intertemporal choice task. Results: Overall, we did not find any effect of serotonin and 5-HTTLPR on temporal discounting rates or the brain networks associated with valuation and cognitive control. Conclusion: Our findings indicate that serotonin may not be directly involved in choices including delays on longer timescales such as days, weeks or months. We speculate that serotonin plays a stronger role in dynamic intertemporal choice tasks where the delays are on a timescale of seconds and hence are therefore directly experienced during the experiment.

No description available.

of the thesis Considerable research attention has been paid to the neural regulation of the lower urinary tract (LUT) in past three decades. The aim of this work is mapping of a brain activity by functional magnetic resonance imaging (fMRI) using refined scanning protocol with synchronously performed urodynamics. We aimed to detect neural activity associated with pelvic floor muscle (PF) contractions, filling of urinary bladder and miction. In addition we evaluated using fMRI brain activity associated with urinary bladder filling in patients with a complete spinal cord injury (SCI). We hypothesized activation of brainstem and forebrain areas in receiving information from the vagal nerves. Adjustments of urodynamic system enabled successful implementation of synchronous filling cystometry with fMRI evaluation of cortical activity. We concluded that synchronous urodynamic examination is a novel feasible method that facilitates and enhance interpretation of fMRI data acquired. The main clusters of brain activation during PF contractions were observed in the medial surface of the frontal lobe (primary motor area) and supplementary motor area (SMA). We detected neural activity associated with filling of urinary bladder and miction in middle and inferior frontal gyrus, angular gyrus, posterior and...

Laut der „Bayesian Brain“-Hypothese ist Wahrnehmung ein Inferenzprozess, der von sensorischen Daten abhängt, aber auch von Vorannahmen über die Wahrscheinlichkeit sensorischer Daten und ihrer Zuverlässigkeit. Feedback aus der Umgebung verbessert das Lernen und hilft dem Gehirn, diesen Inferenzprozess zu optimieren. In vorherigen Arbeiten wurde gezeigt, dass unzuverlässiges Feedback die perzeptuelle Genauigkeit beeinträchtigt und Fehlwahrnehmungen in Rauschsignalen erhöht. In dieser Arbeit wurde die Hypothese untersucht, dass der Effekt von unzuverlässigem Feedback einer geringeren Gewichtung sensorischer Daten im Inferenzprozess entspricht. Hierzu wurden zwei Studien mit visuellen Reizen durchgeführt: Studie I umfasste zwei Verhaltensexperimente; Studie II umfasste ein Experiment mit funktioneller Magnetresonanztomographie. Unter der Annahme einer Abwertung sensorischer Information infolge unzuverlässigen Feedbacks wurde eine Verringerung der perzeptuellen Leistung vorhergesagt und eine Verschiebung der Wahrnehmungsinferenz zu experimentell induzierten Vorannahmen. Auf neuronaler Ebene wurde untersucht, ob sich sensorische Repräsentationen im primären visuellen Kortex (V1) als Folge unzuverlässigen Feedbacks verschlechtern würden. In allen Experimenten wurde in einer Kontrollbedingung zuverlässiges Feedback gegeben. Die Ergebnisse beider Studien zeigten eine Abnahme der perzeptuellen Leistung nach unzuverlässigem versus zuverlässigem Feedback. Darüber hinaus verließen sich die Probanden zunehmend auf induzierte Vorannahmen. Auf neuronaler Ebene zeigte sich eine Verrauschung sensorischer Repräsentationen in V1 als Folge unzuverlässigen Feedbacks. Zusammenfassend zeigt sich, dass die Induzierung von Überzeugungen über die Zuverlässigkeit sensorischer Informationen durch manipuliertes Leistungsfeedback einen systematischen Einfluss auf perzeptuelle Inferenz hat und dass sich diese Veränderungen in frühen sensorischen Arealen manifestieren. / According to the Bayesian brain hypothesis, perception is an inferential process that depends not only on sensory data, but also on our beliefs about likely sensory data and their reliability. Feedback from the environment improves this inferential process. Indeed previous studies have shown that unreliable feedback impairs task performance and increases illusory pattern perception in noise. In this thesis, we explored the hypothesis that the effect of unreliable feedback is a down-weighting of sensory information in perceptual inference. We conducted two studies comprising visual stimuli: Study I comprised two behavioural experiments and Study II comprised a functional magnetic resonance imaging experiment. Based on the hypothesis that sensory data would be down-weighed after unreliable feedback , we predicted that perceptual performance would deteriorate and that perceptual inference would shift towards experimentally induced priors. Further, we investigated whether the sensory data representations in the primary visual cortex (V1) deteriorate as a result of unreliable feedback. Reliable feedback was used as a control condition in all the experiments. Data from both studies demonstrated that performance did decrease following unreliable feedback compared to reliable feedback. Moreover, observers increasingly relied on prior information as the feedback about their percepts became unreliable. At the neural level, low-level stimulus representations deteriorated in V1 with unreliable feedback. To sum up, our results show that inducing beliefs about the reliability of sensory information by manipulating performance feedback can systematically influence perceptual inference and that these changes manifest at the earliest stages of cortical sensory processing.

No description available.

Recently there has been considerable attention directed towards the increased risk for head injuries that athletes face while participating in high impact sports. Furthermore, there is also heightened interest in the asymptomatic sport related sub-concussive blows, commonly experienced during play, that possibly lead to long term neurological deficits. Purpose: The goal of this study was to investigate retired professional athletes of the Canadian Football League with a history of sport-related concussions, using several advanced MRI methods. The ultimate goal being the identification of any potential synergistic effects between a history of sport-related concussions, and exacerbated cognitive decline later on in life. Materials and Methods: Twenty former professional athletes of the Canadian Football League were scanned using a GE Discovery MR750 3T MRI with a 32-channel RF-coil. Axial FSPGR-3D images were used to define rs-BOLD and DTI scans. Seed based network analysis of the DMN was performed on rs-BOLD data. Voxel-wise tensor fitting of DTI data provided the means for estimating several tensor metrics. Results were normalized through comparison with a database of healthy controls. Potential associations between functional connectivity, white matter integrity, and cortical thickness measures were correlated with retired athlete position and years of professional play. Results: We found widespread cortical thinning in retired CFL subjects, alongside significant increases in axial and mean diffusivity in the corona radiata and splenium and genu of the corpus callosum compared to controls. Seed based correlation analysis of the DMN network revealed interrupted connectivity in retired athletes. Athlete age, po- sition, and number of years played appear to be factors in overall core white matter microstructural integrity. Conclusions: When compared to an age and sex matched control population, differences were observed both in functional and structural con- nectivity, suggesting that even years after retiring the brains of these former athletes still exhibit signs of damage. / Thesis / Master of Applied Science (MASc) / Sport-related concussions affect millions of athletes on a yearly basis in the United States alone. Concussions are often accompanied by short-lived neurological impairments, such as confusion, headaches, dizziness, nausea and memory loss. In addition, there is the potential for development of long term mental health and cognitive impairment. The goal of this work was to identify any neurological changes present in retired athletes of the Canadian Football League, through the use of advanced magnetic resonance imaging techniques evaluating thickness of brain structures, changes in brain activity, and alterations in core microstructure of the brain. Analyzing the results of these techniques revealed changes in a number of brain regions within the retired professional athlete population. These results suggest that a career of high impact sports may lead to short term, in addition to long-term neurological consequences.