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The neuropsychology of obsessive-compulsive symptomsHemberger, Helga Christine January 2007 (has links)
Doctor of Clinical Psychology / Obsessive-compulsive (OC) symptoms occur in a variety of clinical conditions, but the underlying pathogenesis of these symptoms remains elusive. Few neuropsychological investigations have compared idiopathic Obsessive-Compulsive Disorder (OCD) with patient groups where OC symptoms are acquired. The present study investigated the neuropsychological correlates of OC symptoms in OCD and frontotemporal dementia (FTD), a neurodegenerative illness in which OC symptoms are often acquired. Neuroimaging in OCD has consistently implicated the frontal-striatal-thalamic circuit, particularly the orbitofrontal cortex and basal ganglia. These areas overlap considerably with the sites of cerebral pathology found in FTD. OCD has been associated with a number of neuropsychological deficits, with most consistent findings pointing towards impaired executive function (EF), and less commonly reported deficits in visual memory and visuospatial ability. The neuropsychological hallmark of FTD is deficits in EF. However in both OCD and FTD, the relationship between cognitive deficits and OC symptoms remains unclear. Further, the extent to which OC symptoms are comparable between the groups is ambiguous. Part I of the present study compared 19 OCD subjects to 20 age, education and IQ-matched healthy controls on a battery of neuropsychological tests of all major cognitive domains with emphasis on EF. A measure of Theory of Mind (ToM) thought to be sensitive to orbitofrontal function was also administered. OCD subjects performed worse than controls on a measure of visual memory, visuospatial reasoning and on only one measure of EF. OCD symptom subtypes, as measured by the Obsessive-Compulsive Inventory (OCI), were not correlated with any cognitive deficits. No group differences in ToM were found. It is suggested that prior research has overestimated the severity and significance of EF deficits in OCD. Part II of the study compared 9 FTD participants with 10 matched healthy controls on the same neuropsychological test battery and OC symptom measures. In addition, a measure of compulsive behaviours used in neurological populations was administered to carers. While the incidence of OC symptoms was comparable to reports in previous studies (78%), the OCI was not sensitive in the detection of OC symptoms in FTD. The similarities and differences in OC symptoms between the two patient groups are discussed.
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Teste de memória integrativa: comparação de desempenho entre demência frontotemporal variante comportamental e doença de Alzheimer / Memory binding test: comparisons between Alzheimer\'s disease and behavioural variant frontotemporal dementiaMário Amore Cecchini 30 November 2017 (has links)
INTRODUÇÃO: O teste de memória integrativa (TMI) de curto prazo, nas modalidades de recordação espontânea (RE) e reconhecimento visual (RV), tem se mostrado promissor para apoiar o diagnóstico precoce da doença de Alzheimer (DA), com grande potencial para aplicação clínica. Até o momento, não foram encontrados estudos sobre o TMI junto à população idosa brasileira, nem tampouco pesquisas utilizando a tarefa de RV em pacientes com a variante comportamental da demência frontotemporal (DFTvc). OBJETIVOS: A presente pesquisa comparou o desempenho de pacientes com DA, pacientes com DFTvc e Controles nas duas modalidades de TMI e examinou a acurácia diagnóstica dos testes para a detecção da DA. MÉTODOS: Foram avaliados participantes de três centros de pesquisa, USP São Paulo, USP Ribeirão Preto e Universidade Federal de Minas Gerais, assim como do Instituto Paulista de Geriatria e Gerontologia. A amostra foi composta por 85 indivíduos, subdivididos em 32 Controles, 35 pacientes com DA e 18 pacientes com DFTvc. Foram geradas curvas ROC para calcular a acura?cia diagno?stica dos testes contrastando os grupos diagno?sticos. Realizou-se análises de regressão logística, de correlação e análises de interação entre diagnóstico e condição experimental (características integradas x não-integradas). RESULTADOS: No TMI com RE, Controles apresentaram resultados semelhantes aos pacientes com DFTvc e os pacientes com DA mostraram resultado significativamente menor em relac?a?o aos dois primeiros grupos (Controles = DFTvc > DA). No TMI com RV, Controles mostraram escores significativamente maiores que os pacientes com DFTvc e DA (Controles > DA = DFTvc). A acurácia diagnóstica do teste de RE para DA foi de 0,853, com sensibilidade e especificidade de 84,4% e 80%, respectivamente. A acurácia diagnóstica do teste de RV para DA foi de 0,809, com sensibilidade e especificidade de 65,4% e 72,2%, respectivamente. As modalidades do TMI mostraram correlação significativa com outros testes neuropsicológicos. A tarefa de RV apresentou correlação maior com testes relacionados as funções executivas e de atencão, enquanto que a tarefa de RE mostrou correlação com testes que avaliam memória episódica e funcões executivas. CONCLUSÕES: O presente estudo demonstrou a aplicabilidade do TMI na população brasileira. As tarefas apresentaram características adequadas para a prática clínica: são fáceis e rápidas de aplicar, necessitam de pouco tempo de aplicação, e podem contribuir para o diagnóstico da DA. Especialmente a tarefe de RE, que foi capaz de diferenciar DA de DFTvc / INTRODUCTION: The free recall (FR) and visual recognition (VR) modalities of the memory binding test (MBT) are promising tools to support the early diagnosis of Alzheimer\'s disease (AD). Until the present moment, no studies have been conducted with these tests among the elderly population in Brazil, and there are no studies with the VR modality of the MBT involving behavioural variant frontetemporal dementia (bvFTD) patients. OBJECTIVES: the present research examined the diagnostic accuracy of the two modalities of the MBT for the detection of AD, and compared the performance of patients with AD, bvFTD and controls. METHODS: Participants of three research centres were assessed, USP São Paulo, USP Ribeirão Preto and Federal University of Minas Gerais, and from the Paulista Institute of Geriatrics and Gerontology. The sample comprised 85 participants: 32 controls, 35 AD and 18 bvFTD patients. ROC analyses were used to examine the diagnostic accuracy of the MBT contrasting the different diagnostic groups. Logistic regression analysis, correlations were calculated. ANOVA analyses tested the interaction between diagnosis and experimental condition (features bound and unbound). RESULTS: In the FR task, controls and bvFTD showed similar results, and AD patients showed worse performance (controls = bvFTD > AD). In the VR task, controls showed better performance than the clinical groups (controls > AD = bvFTD). The diagnostic accuracy of the FR task for AD was 0.853, with 84.4% of sensitivity and 80% of specificity. The diagnosis accuracy of the VR task for AD was 0.809, with 65.4% of sensitivity and 72.2% of specificity. The MBT showed significant correlation with other neuropsychological tests. The VR task correlated with tests associated with executive functions and attention, while the FR task correlated with episodic memory and executive functions. CONCLUSIONS: The present study showed the applicability of the MBT for the Brazilian population. The tasks presented adequate characteristics for clinical use: they are quick to administer and can contribute to the diagnosis of AD. Especially the FR task, that could differentiate AD from bvFTD
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Test of Practical Judgment\" (TOP-J): adaptação brasileira em amostra de indivíduos cognitivamente saudáveis, com comprometimento cognitivo leve e demência / Test of Practical Judgment (TOP-J): Brazilian adaptation in a sample of cognitively healthy individuals, mild cognitive impairment and dementiaPatrícia Helena Figueirêdo do Vale Capucho 07 July 2015 (has links)
INTRODUÇÃO: Julgamento é a capacidade de tomar decisões após cuidadosa consideração das informações disponíveis, soluções possíveis, resultados prováveis e fatores contextuais. Do ponto de vista neuropsicológico, o conceito de julgamento envolve memória, linguagem, atenção, raciocínio e principalmente funções executivas. Perda de julgamento tem sido descrita em Comprometimento Cognitivo Leve (CCL) e demência. O Test of Practical Judgment (TOP-J) é uma medida originalmente americana, desenvolvida para avaliar o julgamento prático em adultos mais velhos. É um questionário aberto de 15 itens (TOP-J/15) ou de 9 itens (TOP-J/9) no qual os participantes escutam breves cenários sobre os problemas cotidianos e relatam em voz alta as soluções propostas. Este estudo teve como objetivos a adaptação do TOP-J para uso no Brasil, a elaboração de uma versão reduzida deste instrumento e verificação da acurácia de ambas a versões em amostra da população brasileira composta de controles cognitivamente saudáveis e pacientes com Comprometimento Cognitivo Leve (CCL), doença de Alzheimer (DA) e demência frontotemporal variante comportamental (DFT). MÉTODOS: A amostra foi composta por 85 indivíduos, com idade mínima de 50 anos e escolaridade mínima de 4 anos, sendo 24 controles, 26 CCL, 20 DA e 15 DFT. Os participantes foram submetidos a avaliação neuropsicológica e ao TOP-J. RESULTADOS: No TOP-J/15 versão brasileira (TOP-J/15-Br) e no TOP-J/9 versão brasileira (TOP-J/9-Br) (versão reduzida), o desempenho de controles foi estatisticamente superior ao desempenho de pacientes com CCL, DA e DFT e o desempenho de CCL foi superior ao de pacientes com DA e DFT. No TOP-J/15-Br, a confiabilidade verificada pelo alfa de Cronbach foi de 0,69 e o melhor ponto de corte para distinção de controles e pacientes foi de 30 (sensibilidade de 91,7%; especificidade de 59% e área sob a curva de 0,80). No TOP-J/9-Br, o alfa de Cronbach foi de 0,68 e o melhor ponto de corte para distinção entre julgamento de controles e de pacientes foi 19, com sensibilidade de 79,2, especificidade de 72,1 e área sob a curva de 0,82. CONCLUSÕES: O TOP-J/15-Br e o TOP-J/9-Br apresentaram características psicométricas robustas para o uso pretendido com amostra da população brasileira. Ambos foram capazes de identificar prejuízo de julgamento já em pacientes com CCL e diferenciaram julgamento de controles do julgamento de pacientes com boa sensibilidade e especificidade / INTRODUCTION: Judgment is the ability to make sound decisions after careful consideration of available information, possible solutions, likely outcomes and contextual factors. From a neuropsychological perspective, the concept of judgment involves memory, language, attention, reasoning and specially the executive functions. Loss of judgment has been described in Mild Cognitive Impairment (MCI) and dementia. The Test of Practical Judgment (TOP-J) is an originally American measure created for evaluate practical judgment in older adults. It is a 15-item (TOP-J/15) or 9- item (TOP-J/9) open-ended questionnaire in which participants listen to brief scenarios about everyday problems and report aloud their proposed solutions. This study aimed the adaptation of the TOP-J for use in Brazil, the development of a reduced version of this instrument and the verification of accuracy of both the versions in Brazilian sample composed of cognitively healthy controls and patients with mild cognitive impairment (MCI), Alzheimer\'s disease (AD) and frontotemporal dementia behavioral variant (FTD). METHODS: The sample consisted of 85 subjects with a minimum age of 50 years and minimum education of 4 years, being 24 controls, 26 MCI, 20 AD e 15 FTD. The participants were submitted to a neuropsychological assessment and TOP-J. RESULTS: In the TOP-J/15 Brazilian version (TOP-J/15-Br) and in the TOP-J/9 Brazilian version (TOP-J/9-Br) (reduced version), performance of controls was statistically better than the performance of MCI, AD and FTD patients, and performance of MCI was statistically better than AD and FTD patients. In TOP-J/15-Br, the reliability verified by Cronbach\'s alpha was 0.69 and the best cutoff for distinction between controls and patients was 30 (sensibility of 91,7%; specificity of 59% and area under the curve of 0,8). In the TOP-J/9-Br, Cronbach\'s alpha was 0.68 and the best cutoff point for distinguishing between judgment of controls and judgment of patients is 19, with a sensitivity of 79,2, specificity of 72,1 and area under the curve of 0.82. CONCLUSIONS: The TOP-J/15-Br and the TOP-J/9-Br showed robust psychometric characteristics for the intended use with a sample of the Brazilian population. Both were able to identify deficits of impaired of judgment already in patients with MCI and were able to distinguish judgment of controls from judgment of patients with good sensitivity and specificity
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Resting-state functional MRI in behavioral variant of frontotemporal dementiaRytty, R. (Riikka) 12 April 2016 (has links)
Abstract
Frontotemporal lobar degeneration (FTLD) is the second most common neurodegenerative disease leading to early-onset dementia with an estimated worldwide prevalence of 10 to 30 cases per 100000 individuals in the age group of 46 to 65 years. Behavioral variant frontotemporal dementia (bvFTD) is the most common FTLD subtype. It is characterized by a progressive deterioration of behavior and personality as well as executive dysfunction. In Finland, almost 50 % of familial FTLD cases are attributable to the C9ORF72 mutation.
bvFTD is associated with a characteristic pattern of brain atrophy detectable in structural MRI. However, these changes are typically not visible in the early stages of the disease. Resting-state functional MRI (RS-fMRI) is being increasingly used to evaluate changes in functional connectivity within neuronal networks in the brain but only a few RS-fMRI investigations of bvFTD patients have been published with inconsistent results.
The object of this thesis was to investigate functional connectivity changes detected in the salience (SLN) and default mode networks (DMN) in bvFTD. Another aim was to clarify the role of other cognitive resting-state networks in this disease.
A cohort of 26 bvFTD patients was studied, with 8 of these patients carrying the C9ORF72 expansion. Connectivity changes were detected in multiple clinically relevant cognitive networks. Decreased functional connectivity was observed in the SLN, which is associated with guiding of behavior. Increased activity was present in the DMN and the dorsal attention network (DAN). In C9ORF72 associated bvFTD, there was an abnormal linkage detected between the DMN and the thalamus.
Currently, fMRI is generally used as a research tool and in a group setting. Different study methods have been used in the literature and also in the studies of this thesis, the analysis procedures differed to some extent. The variety of analysis methods may explain the heterogeneity in fMRI findings in bvFTD patients. There is a need for standardization of the fMRI methodology, larger study groups and also in the future the methodology should be improved so that single patient analysis would provide results to allow a confident diagnosis of this disease. / Tiivistelmä
Otsa-ohimolohkorappeuma (Frontotemporal lobar degeneration, FTLD) on toiseksi yleisin etenevä dementiaan johtava sairaus, joka ilmaantuu usein jo työikäisenä. Otsalohkodementia on otsa-ohimolohkorappeuman yleisin alamuoto, jonka oireisto painottuu persoonan ja käyttäytymisen muutoksiin sekä toiminnan ohjauksen ongelmiin. Suomessa C9ORF72-toistojaksomutaatio selittää lähes 50 % perinnöllisistä otsa-ohimolohkorappeumista.
Aivojen rakenteellisella magneettikuvauksella (MK) voidaan havaita rakenteellisia muutoksia, jotka ilmaantuvat kuitenkin vasta taudin edettyä vaikeampaan vaiheeseen. Aivojen lepotilan toiminnallinen magneettikuvaus (TMK) mahdollistaa aivojen hermoverkkojen toiminnan eli konnektiviteetin kartoituksen. Aiemmin TMK:a on tutkittu esim. Alzheimerin taudissa. Otsalohkodementiassa TMK:sta on julkaistu ainoastaan yksittäisiä tutkimuksia ja tulokset ovat olleet osin ristiriitaisia.
Väitöskirjatutkimuksen tarkoituksena on ollut selvittää valve-lepotilan hermoverkossa ja olennaisen tunnistavassa hermoverkossa tapahtuvia muutoksia otsalohkodementiaa sairastavilla potilailla. Toisena tavoitteena on ollut tutkia muissa kognitiivisissa hermoverkoissa tapahtuvia muutoksia.
Otsalohkodementiaa sairastaville potilaille (n= 26) sekä ikä- ja sukupuolivakioiduille kontrolleille on tehty kliininen tutkimus ja rakenteellinen sekä toiminnallinen aivojen magneettikuvaus. Kahdeksalla potilaalla todettiin C9ORF72-toistojaksomutaatio. Useiden kognitiivisten hermoverkkojen toiminnassa havaittiin muutoksia, jotka korreloivat potilaiden kliinisiin oireisiin. Alentunutta konnektiviteettia todettiin olennaisen tunnistavassa hermoverkossa, joka osallistuu käyttäytymisen säätelyyn. Lisääntynyttä konnektiviteettia esiintyi valve-lepotilan hermoverkossa ja tarkkaavaisuus hermoverkossa. Potilailla, joilla on C9ORF72-mutaatio, havaittiin epänormaali yhteys valve-lepotilan hermoverkon ja talamuksen välillä.
TMK:ta käytetään tällä hetkellä lähinnä tutkimustyökaluna. Analyysityökaluissa on ollut vaihtelevuutta eri julkaisuissa ja osin myös tämän väitöskirjan osatöissä. Julkaistut TMK-löydökset otsalohkodementiassa ovat osin ristiriitaisia ja se saattaa selittyä erilaisilla analyysimenetelmillä. Metodologiaa tulisi standardisoida ja lisäksi tarvitaan suurempia potilasryhmiä ja menetelmien kehittämistä, jotta TMK:n käyttö yksilötason kliinisessä diagnostiikassa olisi jatkossa mahdollista.
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Orbitofrontal Dysfunction Related to Both Apathy and Disinhibition in Frontotemporal DementiaPeters, Frédéric, Perani, Daniela, Herholz, Karl, Holthoff, Vjera, Beuthien-Baumann, Bettina, Sorbi, Sandro, Pupi, Alberto, Degueldre, Christian, Lemaire, Christian, Collette, Fabienne, Salmon, Eric January 2006 (has links)
Orbitofrontal metabolic impairment is characteristic of the frontal variant of frontotemporal dementia (fv-FTD), as are early changes in emotional and social conduct. Two main types of behavioral disturbances have been distinguished in fv-FTD patients: apathetic and disinhibited manifestations. In this study, we searched for relationships between brain metabolism and presence of apathetic or disinhibited behavior. Metabolic activity and behavioral data were collected in 41 fv-FTD patients from European PET centers. A conjunction analysis of the PET data showed an expected impairment of metabolic activity in the anterior cingulate, ventromedial and orbital prefrontal cortex, the dorsolateral prefrontal cortex and the left anterior insula in fv-FTD subjects compared to matched controls. A correlation was observed between disinhibition scores on the Neuropsychiatric Inventory scale and a cluster of voxels located in the posterior orbitofrontal cortex (6, 28, –24). Comparison of brain activity between apathetic and nonapathetic fv-FTD patients from two centers also revealed a specific involvement of the posterior orbitofrontal cortex in apathetic subjects (4, 22, –22). The results confirm that the main cerebral metabolic impairment in fv-FTD patients affects areas specializing in emotional evaluation and demonstrate that decreased orbitofrontal activity is related to both disinhibited and apathetic syndromes in fv-FTD. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Investigation of RNA Binding Protein Pumilio as a Genetic Modifier of Mutant CHMP2B in Frontotemporal Dementia (FTD): A Masters ThesisDu, Xing 14 August 2016 (has links)
Frontotemporal dementia (FTD) is the second most common early-onset dementia. A rare mutation in CHMP2B gene was found to be associated with FTD linked to chromosome 3. Previous studies have shown that mutant CHMP2B could lead to impaired autophagy pathway and altered RNA metabolism. However, it is still unknown what genes mediate the crosstalk between different pathways affected by mutant CHMP2B. Genetic screens designed to identify genes interacting with mutant CHMP2B represents a key approach in solving the puzzle. Expression of mutant CHMP2B (CHMP2Bintron5) in Drosophila eyes leads to a neurodegenerative phenotype including melanin deposition and disrupted internal structure of ommatidia. The phenotype is easily quantified by estimating the percentage of black dots on the surface of the eyes. Using this established Drosophila model, I searched for genes encoding RNA binding proteins that genetically modify CHMP2Bintron5 toxicity. I found that partial loss of Pumilio, a translation repressor, mitigates CHMP2Bintron5 induced toxicity in the fly eyes. Western blot analysis showed that down regulation of Pumilio does not significantly decrease CHMP2Bintron5 protein level, indicating indirect regulation involved in suppression of the phenotype. The molecular targets regulated by Pumilio and the mechanism underlying CHMP2Bintron5 toxicity suppression by Pumilio down-regulation requires further investigation.
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La régulation de G3BP1 par TDP-43 dans le contexte de la sclérose latérale amyotrophique et la démence fronto-temporaleSidibé, Hadjara 12 1900 (has links)
La sclérose latérale amyotrophique (SLA) et la démence fronto-temporale (DFT) sont des maladies neurodégénératives fatales, actuellement sans traitement. Ces maladies entrainent la dégénérescence des neurones moteurs et corticaux, engendrant des troubles moteurs et cognitifs et ultimement menant à la mort des patients souvent par détresse respiratoire trois à cinq ans après l’apparition des premiers symptômes. À l’échelle d’une vie, le risque de développer ces pathologies est de 1 pour 300-400 pour la SLA et 1 pour 742 pour la DFT, faisant de ces pathologies un risque majeur. Avec le vieillissement de la population que nous connaissons actuellement, il est évident que l’incidence de ces maladies deviendra de plus en plus élevée. Ainsi il est essentiel de comprendre les mécanismes moléculaires sous-jacents à ces pathologies dans le but de développer des thérapies effectives et prévenir l’impact de ces pathologies dans notre société. À ce jour, l’étiologie de la SLA-DFT est encore débattue, cependant la communauté scientifique s’accorde sur le fait que l’interaction entre la génétique et l’environnement joue un rôle essentiel dans le développement de ces maladies. La caractéristique moléculaire principale de ces pathologies est la localisation cytoplasmique de la protéine, normalement, nucléaire TDP-43. TDP-43 est un régulateur clef de l’homéostasie des ARNs. Parmi ces nombreuses fonctions, TDP-43 régule la formation des granules de stress, en régulant leur protéine régulatrice G3BP1. Ces granules formés d’ARN et de protéines se forment pour protéger les cellules durant une période de stress. Récemment, ces granules ont fait l’objet de nombreuses études et leurs dysfonctions ont été associées à la SLA-DFT. Dans cette thèse, nous avons approfondi l’étude de la régulation de TDP-43 sur G3BP1. Nous avons défini que TDP-43 stabilise les transcrits de G3BP1 de par une liaison forte à une séquence conservée à travers l’évolution se situant dans le 3’UTR de G3BP1. La perte de localisation nucléaire, la présence de mutations ou de TDP-35, une isoforme pathologique de TDP-43, sont associées à une diminution des niveaux de G3BP1. Également, d’un point de vue histopathologique, dans le cortex orbitofrontal des patients atteints de SLA-DFT, les neurones présentant une localisation cytoplasmique de TDP-43 ont une perte des niveaux transcriptionnels de G3BP1, associant alors directement G3BP1 à la maladie. Par la suite, nous avons défini que la perte de fonction en tant que stabilisateur, permet la liaison de microARNs sur les transcrits de G3BP1, engendrant leur dégradation. Le blocage de la liaison de microARNs sur G3BP1 empêche la dégradation des transcrits et restaure les fonctions de la protéine. Ainsi, nous avons déterminé un moyen de contrer la perte de fonction de TDP-43 sur G3BP1. De façon intéressante, en plus de la formation des granules de stress, G3BP1 est essentielle pour l’homéostasie neuronale et la survie neuronale post-stress. Par conséquent, la restauration de la protéine est potentiellement une avenue thérapeutique multi-approche pour le traitement de ces maladies. / Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two fatal neurodegenerative diseases, currently without cure. These diseases lead to the degeneration of motor and cortical neurons, causing motor and cognitive disorders and ultimately leading to death, often from respiratory distress three to five years after the onset. Over a lifetime, the risk of
developing these conditions is 1 in 300-400 for ALS and 1 in 742 for FTD, making these conditions a major risk. With the current aging of the population, it is evident that the incidence of these diseases will become increasingly high. It is therefore essential to understand the molecular mechanisms underlying these pathologies in order to develop effective therapies. To this day, the etiology of ALS-FTD is still debated. However, the scientific community agrees that the interaction between genetics and the environment play an essential role in the development of these diseases. The main molecular characteristic of these pathologies is the cytoplasmic localization of the normally nuclear protein TDP-43. TDP-43 is a key regulator of RNA homoeostasis. Among these many functions, TDP-43 regulates the formation of stress granules,
by regulating their nucleator protein G3BP1. These granules of RNA and protein form to protect cells during times of stress. Recently these granules have been the subject of several studies and their dysfunction has been associated with ALS-FTD.
In this thesis, we have deepened the study of the regulation of TDP-43 on G3BP1. We have defined that TDP-43 stabilizes G3BP1 transcripts by strong binding to a sequence conserved through evolution located in the 3'UTR of G3BP1. Loss of nuclear localization, the presence of mutations or of TDP-35, a pathological isoform of TDP-43, are associated with decreased levels of G3BP1. Also, histopathologically, in the orbitofrontal cortex of patients with ALS-DFT, neurons with cytoplasmic localization of TDP-43 have a loss of transcriptional levels of G3BP1, directly associating G3BP1 with the disease. Subsequently, we defined that TDP-43 loss of function as a stabilizer allows the binding of two microRNAs on the G3BP1 transcripts, causing their degradation. Blocking the binding of these microRNAs to G3BP1 prevents the degradation
of the transcripts and restores the functions of the protein. Thus, we have determined a way to counter the loss of function of TDP-43 on G3BP1. Interestingly, in addition to the formation of stress granules, G3BP1 is essential for neuronal homoeostasis and post-stress neuronal survival. Therefore, the restoration of the protein is potentially a multi-approach therapeutic avenue for the treatment of these diseases.
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A critical analysis of the present neuropsychological and neuroanatomical theories and knowledge of art perception and artistic production taking creativity into accountRomp, Andreas Johannes 01 1900 (has links)
Text in English / The present paper analyses the neuroanatomical and neuropsychological backgrounds of art reception and art creation in modern visual art and creative processes. It critically presents two models of aesthetic experience to provide a comprehensive theoretical basis for the discussion. The research purpose is to show
that with increasing experience and expertise the referential frame of the aesthetic judgment is changing and that neural processes involved in object recognition provide a starting point for visual aesthetics. Thus, the investigation focuses on constructing and testing neuropsychological theories that fall in the domain called
'neuroaesthetics'. These theories, in turn, serve as a starting point to formulate neural laws of art and aesthetics and aesthetic experience. Some artistic styles, such as expressionism, reflect specific neural processes. Various studies indicate correlations between hemispheric specialisation and art or creativity and show the right hemisphere plays a particular role in it. However, studies exploring the neural
correlates of aesthetic preference have yielded mixed results. Furthermore, neuroimaging studies have proved that different categories of modern artworks are processed in different areas of the brain. These diverging results will be discussed in a critical assessment of the two models of aesthetic experience. Besides, the
question of identifying exclusive neural correlates of aesthetic preference will be raised.
Comparing amateurs and experts has revealed the more reduced the cortical
activation, the more efficiently it works.
Biological and neuropsychological factors of creativity point out the meaning of the activation level, cognitive inhibition and prefrontal cortex. Divergent thinking differs from convergent thinking in terms of the neural level.
Neurodegenerative processes and brain injuries sometimes influence the artistic output surprisingly or even launch it. Lesion studies contributing to understanding art experience will be explained. / Psychology / M.A. (Psychology)
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A critical analysis of the present neuropsychological and neuroanatomical theories and knowledge of art perception and artistic production taking creativity into accountRomp, Andreas Johannes 01 1900 (has links)
The present paper analyses the neuroanatomical and neuropsychological backgrounds of art reception and art creation in modern visual art and creative processes. It critically presents two models of aesthetic experience to provide a comprehensive theoretical basis for the discussion. The research purpose is to show
that with increasing experience and expertise the referential frame of the aesthetic judgment is changing and that neural processes involved in object recognition provide a starting point for visual aesthetics. Thus, the investigation focuses on constructing and testing neuropsychological theories that fall in the domain called
'neuroaesthetics'. These theories, in turn, serve as a starting point to formulate neural laws of art and aesthetics and aesthetic experience. Some artistic styles, such as expressionism, reflect specific neural processes. Various studies indicate correlations between hemispheric specialisation and art or creativity and show the right hemisphere plays a particular role in it. However, studies exploring the neural
correlates of aesthetic preference have yielded mixed results. Furthermore, neuroimaging studies have proved that different categories of modern artworks are processed in different areas of the brain. These diverging results will be discussed in a critical assessment of the two models of aesthetic experience. Besides, the
question of identifying exclusive neural correlates of aesthetic preference will be raised.
Comparing amateurs and experts has revealed the more reduced the cortical
activation, the more efficiently it works.
Biological and neuropsychological factors of creativity point out the meaning of the activation level, cognitive inhibition and prefrontal cortex. Divergent thinking differs from convergent thinking in terms of the neural level.
Neurodegenerative processes and brain injuries sometimes influence the artistic output surprisingly or even launch it. Lesion studies contributing to understanding art experience will be explained. / Psychology / M.A. (Psychology)
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Frontotemporal lobar degeneration in Finland:molecular genetics and clinical aspectsKaivorinne, A.-L. (Anna-Lotta) 20 November 2012 (has links)
Abstract
Frontotemporal lobar degeneration (FTLD) is the second most common neurodegenerative disease leading to early-onset dementia (< 65 years), next to Alzheimer’s disease. FTLD is substantially a genetic disorder with up to 50% of cases having a positive family history. Mutations in the genes microtubule-associated protein tau (MAPT) and progranulin (PGRN) account for about 10–20% of all cases of FTLD. Hexanucleotide repeat expansion mutation within the gene C9ORF72 has recently been identified as the major cause of FTLD, FTLD with amyotrophic lateral sclerosis (ALS) and pure ALS. During this study, hexanucleotide repeat expansion within the C9ORF72 gene was shown to explain nearly 50% of familial and 30% of all FTLD cases in the Finnish population. Otherwise, the genetic background of Finnish FTLD is largely unknown.
The object of the present work was to disentangle the genetic aetiology of FTLD in the Finnish population. We studied a cohort of patients with a clinical diagnosis of FTLD from the province of Northern Ostrobothnia, Finland. Sequencing analysis of the genes MAPT, charged multi-vesicular body protein 2B (CHMP2B) and TAR DNA binding protein (TARDBP) were performed and the MAPT haplotypes were analysed. Correlations between genotype and phenotype were studied in patients with C9ORF72 repeat expansion mutation.
C9ORF72 expansion mutation explained nearly 30% of cases of FTLD in our cohort. Concomitant ALS and positive family history of the disease increased the possibility of carrying expanded C9ORF72. The clinical phenotype of C9ORF72 expansion carriers varied at presentation: both behavioural and language variants were detected with or without ALS. The behavioural presentations included prominent psychotic features, although psychiatric presentations were not overrepresented in expansion carriers. No pathogenic mutations were identified in the MAPT, CHMP2B and TARDBP genes in our series of FTLD patients. The H2 MAPT haplotype was associated with FTLD in the series.
Our findings emphasise the importance of C9ORF72 expansion mutation in FTLD. While mutations in MAPT and PGRN cause a significant proportion of cases of FTLD worldwide, they seem to be rare causes of FTLD in the Finnish population. Besides being infrequent in other populations, mutations in CHMP2B and TARDBP are rare causes of FTLD in the Finnish population as well. Our findings have clinical implications for recognising phenotypic features characteristic of expanded C9ORF72 as well as for genetic counselling of Finnish patients with FTLD. Even though a considerable proportion of our cases of familial FTLD is caused by the C9ORF72 expansion, over 50 % of our familial cases are without a molecular genetic diagnosis, suggesting that there are other unidentified causal genes to be found. / Tiivistelmä
Otsa-ohimolohkorappeumat on toiseksi yleisin työikäisten dementiaa aiheuttava etenevä aivojen rappeumasairaus. Toisinaan otsa-ohimolohkorappeumat esiintyvät yhdessä liikehermorappeuman, amyotrofisen lateraaliskleroosin (ALS), kanssa. Perinnöllisillä tekijöillä on todennäköisesti keskeinen merkitys taudin taustalla. Mutaatiot microtubule-associated protein tau (MAPT)- ja progranulin (PGRN) geeneissä aiheuttavat yhteensä 10–20 % otsa-ohimolohkorappeumista maailmalla. C9ORF72-geenissä sijaitsevan toistojaksomonistuman on vastikään todettu olevan yleisin otsa-ohimolohkorappeumia ja ALS:a aiheuttava mutaatio. Mutaatio on erityisen yleinen suomalaisessa väestössä selittäen lähes 50 % suvuittaisista ja 30 % kaikista otsa-ohimolohkorappeumista. Oireyhtymän perinnöllisyys on muutoin huonosti tunnettu suomalaisessa väestössä.
Tutkimuksen tavoitteena oli selvittää otsa-ohimolohkorappeumien geneettisiä syitä aineistossa, joka koostui vuosina 1999–2010 Oulun yliopistollisessa sairaalassa tutkituista potilaista. Tutkimuksessa selvitettiin MAPT-, charged multi-vesicular body protein 2B (CHMP2B)- ja TAR DNA-binding protein (TARDBP) geenien mutaatioiden esiintyvyyttä ja määritettiin MAPT-geenin haplotyypit. Lisäksi tutkittiin taudin kliinisiä erityispiirteitä C9ORF72-mutaation kantajilla.
C9ORF72-mutaatio selitti lähes 30 % otsa-ohimolohkorappeumista aineistossamme. Tutkimuksessa havaittiin, että suvuittain esiintyvä tautimuoto ja ALS yhdistyneenä otsa-ohimolohkorappeumaan liittyivät merkittävästi C9ORF72-mutaatioon. Monistuman kantajien fenotyyppi oli moninainen – ensioireina oli sekä käytösongelmia että kielellisiä vaikeuksia. Vaikka C9ORF72-mutaation kantajilla on kuvattu runsaasti psykoottisia oireita, psykoottiset oireet eivät olleet selvästi yliedustettuna mutaation kantajilla aineistossamme. Tutkimuksessa ei löydetty tautia aiheuttavia mutaatioita MAPT-, CHMP2B- tai TARDBP-geeneistä. Havaitsimme kuitenkin tilastollisesti merkittävän yhteyden MAPT-geenin H2-haplotyypin ja otsa-ohimolohkorappeumien välillä.
Tuloksemme antavat uutta tietoa C9ORF72-mutaation kantajien kliinisistä erityispiirteistä. MAPT-geenin mutaatioiden merkitys otsa-ohimolohkorappeumien synnyssä ei näyttäisi olevan suomalaisessa väestössä niin merkittävä kuin muissa väestöissä. CHMP2B- ja TARDBP-mutaatiot ovat harvinainen oireyhtymän syy myös suomalaisessa väestössä. Tuloksiamme voidaan hyödyntää suomalaisten otsa-ohimolohkorappeumapotilaiden perinnöllisessä neuvonnassa. Huomattavista edistysaskelista huolimatta yli puolet suvuittain esiintyvistä tautitapauksistamme on vailla geneettistä diagnoosia, mikä antaa aihetta jatkotutkimuksille.
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