1,721,134 research outputs found
The Combination of DAT-SPECT, Structural and Diffusion MRI Predicts Clinical Progression in Parkinson’s Disease
Full text linkThere is an increasing interest in identifying non-invasive biomarkers of disease severityand prognosis in idiopathic Parkinson’s disease (PD). Dopamine-transporter SPECT(DAT-SPECT), diffusion tensor imaging (DTI), and structural magnetic resonance imaging(sMRI) provide unique information about the brain’s neurotransmitter and microstructuralproperties. In this study, we evaluate the relative and combined capability of theseimaging modalities to predict symptom severity and clinical progression inde novoPDpatients. To this end, we used MRI, SPECT, and clinical data ofde novodrug-naïvePD patients (n= 205, mean age 61±10) and age-, sex-matched healthy controls(n= 105, mean age 58±12) acquired at baseline. Moreover, we employed clinical dataacquired at 1 year follow-up for PD patients with or withoutL-Dopa treatment in orderto predict the progression symptoms severity. Voxel-based group comparisons andcovariance analyses were applied to characterize baseline disease-related alterations forDAT-SPECT, DTI, and sMRI. Cortical and subcortical alterations inde novoPD patientswere found in all evaluated imaging modalities, in line with previously reported midbrain-striato-cortical network alterations. The combination of these imaging alterations wasreliably linked to clinical severity and disease progression at 1 year follow-up in thispatient population, providing evidence for the potential use of these modalities asimaging biomarkers for disease severity and prognosis that can be integrated intoclinical trials
Improved segmentation of deep brain grey matter structures using magnetization transfer (MT) parameter maps
No full textAbstractBasal ganglia and brain stem nuclei are involved in the pathophysiology of various neurological and neuropsychiatric disorders. Currently available structural T1-weighted (T1w) magnetic resonance images do not provide sufficient contrast for reliable automated segmentation of various subcortical grey matter structures. We use a novel, semi-quantitative magnetization transfer (MT) imaging protocol that overcomes limitations in T1w images, which are mainly due to their sensitivity to the high iron content in subcortical grey matter. We demonstrate improved automated segmentation of putamen, pallidum, pulvinar and substantia nigra using MT images. A comparison with segmentation of high-quality T1w images was performed in 49 healthy subjects. Our results show that MT maps are highly suitable for automated segmentation, and so for multi-subject morphometric studies with a focus on subcortical structures
Parkinson's disease may disrupt overlapping sûbthalamic nucleus and pallidal motor networks
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Does music training provide non-musical benefits?: Evidence from auditory, linguistic, and socio-emotional processing
Full text linkThere is a growing body of research on the potential non-musical effects of music training. While transfer to domains tightly related to music (near transfer) are often taken for granted, the possibility of far transfer (to domains substantially different from music) remains controversial. Given the close associations between music, cognitive and socio-emotional processing, we focus on three topics: (1) a systematic review and meta-analysis of longitudinal studies on neural and behavioral effects of music training on auditory and linguistic processing. We report a positive neurobehavioral enhancement of music training on both domains with a small effect size, high levels of heterogeneity and suggestive evidence of publication bias; (2) a cross-sectional study analyzing associations between children’s emotion recognition skills and socio-emotional adjustment. Higher emotion recognition in prosody is associated with better socio-emotional adjustment, even after accounting for cognitive and socio-demographic factors; and (3) a longitudinal study with children investigating music training effects on near transfer domains (auditory and motor skills), and on a wide range of socio-emotional abilities (far transfer). Music training significantly improved motor skills. Effects on auditory skills were inconclusive, however, and we found no effects of music training on socio-emotional processing. These results are suggestive of near transfer from music training, but not of far transfer. Altogether, these findings advance new knowledge on the extent of music training transfer effects, particularly considering children´s socio-emotional abilities, a topic poorly explored.Existem cada vez mais estudos focados nos efeitos de transferência do treino musical. Enquanto possíveis efeitos em domínios próximos da música são frequentemente negligenciados, a possibilidade de transferência para domínios substancialmente diferentes da música é controversa. Considerando a estreita associação entre música, processamento cognitivo, e processamento sócio-emocional, a presente tese foca-se em três tópicos: (1) uma revisão sistemática e meta-análise de estudos longitudinais que examinam efeitos de transferência no processamento auditivo e linguístico, ao nível cerebral e comportamental. Os resultados apontam para um efeito positivo em ambos os domínios. Contudo, o tamanho do efeito é pequeno, existe elevada heterogeneidade, e evidência sugestiva de viés de publicação; (2) um estudo transversal que analisa associações entre o reconhecimento emocional em crianças e o seu ajustamento sócio-emocional. Um melhor reconhecimento emocional em prosódia está positivamente associado ao ajustamento sócio-emocional, independentemente de fatores cognitivos e sócio-demográficos; e (3) um estudo longitudinal com crianças que examina efeitos do treino musical em domínios próximos da música (competências auditivas e motoras), assim como uma ampla variedade de competências sócio-emocionais. O treino musical melhorou significativamente as competências motoras. Contudo, os efeitos nas competências auditivas são inconclusivos e não houve efeitos significativos no processamento sócio-emocional. Estes resultados sugerem que o treino musical pode ter efeitos em domínios próximos da música, mas a evidência para efeitos em domínios substancialmente diferentes da música é escassa. Globalmente, estes resultados permitem avançar novos conhecimentos quanto aos efeitos de transferência do treino musical, particularmente considerando as competências sócio-emocionais de crianças, um tópico pouco explorado
Bayesian modeling of brain function and behavior
No full textThe application of Bayesian modeling techniques is increasingly common in neuroscience due to the coherent and principled way in which the paradigm deals with uncertainty. The Bayesian framework is particularly valuable in the context of complex, ill-posed generative problems, in which case the incorporation of prior knowledge is optimal and practical. If one wants to take full advantage of joint imaging and behavioral data, the need for comprehensive generative models is evident. Here, I exploited the versatility afforded by Bayesian modeling approaches to investigate a series of questions from clinical, systems, and cognitive neuroscience. First, I investigated the lateralization of the cortical motor network in Parkinson's disease patients on and off dopaminergic medication with fMRI and dynamic causal modeling (DCM). Group-level model comparison revealed that disease and medication effects differentially involve homotopic cortical motor connections, but medication does not appear to have a restorative effect at the systems level. Our findings suggest the presence of maladaptive mechanisms, resulting from disease progression and long-term dopamine replacement. In a second project, I considered the way in which humans handle uncertainty in the parameters of the generative model of a task at hand. Using a novel psychophysics paradigm, participants' responses to fitting a parabola to a set of noisy points were compared to the predictions of a set of regression models, including Bayesian regression and several sub-optimal models. Only Bayesian regression could explain participants' response distributions across various levels of sensory uncertainty, suggesting that humans process parameter uncertainty in accordance with Bayesian regression. This finding deepens our understanding of the way in which humans learn and generalize from sparse, ambiguous data. The topic investigated in the greatest depth in this thesis was visual crowding - the deterioration of target discrimination due to the presence of flanking objects. Traditionally, vision is modeled as a feedforward, hierarchical network. Thus, crowding is explained as a pooling of neighboring elements' features, leading to a "bottleneck" at the earliest stages of vision. However, additional flankers can paradoxically improve performance (uncrowding). First, I used DCM and fMRI to show that recurrent processing is crucial for crowding and un-crowding alike. Higher visual areas modulate the lower areas, suggesting that explicit object representation plays a key role. I then used population receptive field (pRF) mapping to investigate the effects of context on pRF size. In accordance with pooling model predictions, the pRF size in crowding is larger than in the case of no crowding. However, in uncrowding, the pRF size is smaller than in crowding and no crowding, providing further evidence against purely feedforward models. Overall, my findings provide strong empirical evidence of context-dependent feedback modulation in vision. I propose a possible implementation which integrates the observed findings into a generative model of crowding: context-agnostic feedforward mechanisms transmit the information about the target and flankers retinotopically to higher visual areas; a subsequent context-dependent feedback pRF determines whether the target will be enhanced - by decreasing the pRF size - or suppressed - by enlarging the pRF size to encompass flankers.LPS
EFFECT OF ELECTROCONVULSIVE THERAPY FOR MAJOR DEPRESSION ON BRAIN VOLUME AND MICROSTRUCTURAL PROPERTIES
No full textMajor depressive disorder (MDD) affects worldwide more than 300 million individuals and is the second contributor to the Years Lived with Disability (DALY). Despite a large therapeutic arsenal, significant number of patients does not recover sufficiently swift from a depressive episode and suffer for a prolonged period of time. For these patients, electroconvulsive therapy (ECT) is the most efficient somatic treatment though its precise mechanism of action is still unknown. Pre-clinical studies indicate that neuroplasticity, and in particular neurogenesis in the hippocampus (HP), are possibly related to the treatment effect. This notion is also supported by human studies that consistently demonstrate hippocampal volume increases in patients undergoing ECT.
In the first part of my project, I sought answering the question whether the observed grey matter (GM) volume increase related to ECT are differentially distributed along HPs longitudinal axis with a predominant effect on the anterior “limbic” portion of the HP. To this aim, 9 MDD patients treated with ECT were scanned before and after ECT. According to our hypothesis, we found a strong spatial effect of ECT induced GM volume change along the main HP axis indicating that the anterior part of the HP is more strongly affected by ECT. Individuals’ clinical outcome was associated with volume changes in the anterior and not in the posterior HP. This study shows that the effect of ECT is not uniform but depends on the position along the longitudinal axis of the HP and indicates the importance of the anterior HP for the mechanism of action of ECT.
In the second part of my project, I tried to address some potential bias in current computational anatomy studies that have limited the straightforward neurobiological interpretation of the observed ECT induced brain changes. Indeed, volume estimation based on T1-weighted contrast is not only influenced my macrostructural changes of brain anatomy but is also influenced by microstructural properties of the brain tissue (the water, myelin and iron content). Therefore, we used advanced MRI acquisition in a new sample of 9 patients to perform a quantitative investigation of the contribution of GM volume, water, myelin and iron to the plasticity occurring during a treatment of ECT. We observed increase of GM volume in the HP and in the anterior cingulate without notable change in microstructural properties. We also found that a widespread pattern of regions including the medial prefrontal cortex, the bilateral HP, the bilateral striatum, and the precuneus were associated with clinical outcome. Interestingly, in the medial PFC we found a large contribution of water and myelin content but no contribution of GM volume, which means that classical morphometric studies would be blind to this association. My findings indicate the potential of quantitative MRI to enhance our understanding of the biological processes underlying the therapeutic effects of ECT in MDD patients.
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La dépression majeure affecte 300 millions d’individus et est le deuxième contributeur aux nombres d’années de vie corrigées de l’incapacité (DALY) au niveau mondial. Malgré un grand arsenal thérapeutique, un nombre important de patients ne répondent pas suffisamment aux traitements et souffrent pour une période prolongée. Pour ces patients, l’électro- convulsivothérapie (ECT) est le meilleur traitement dans cette situation bien que son mécanisme d’action soit mal compris. Des études pré-cliniques indiquent que la neuroplasticité, et en particulier la neurogenèse dans l’hippocampe (HP), sont des élément clé du mécanisme d’action de l’ECT. Cette hypothèse est aussi supportée par des études cliniques qui ont démontré e manière consistente que le volume de l’HP est augmenté chez les patients recevant de l’ECT.
Dans la première partie de ma recherche, j’ai cherché à répondre à la question de savoir si l’augmentation de volume de matière grise causé par l’ECT est distribuée de manière différentielle le long de l’axe longitudinal de l’HP, avec l’hypothèse que l’effet est prédominant sur la partie antérieure ou « limbique » de l’HP. Dans ce but, 9 patients traités par ECT ont été scannés avant et après l’ECT. En accord avec notre hypothèse, nous avons trouvé une forte dépendance spatiale du changement de volume lié à l’ECT par rapport à la position le long de l’axe longitudinal de l’HP, la partie antérieure de l’HP étant la plus susceptible aux effets de l’ECT. De plus, nous avons trouvé que l’état clinique était associé avec la plasticité dans la partie antérieure mais pas postérieure de l’HP. Cette étude met en avant le fait que l’effet de l’ECT n’est pas uniforme mais dépend de la position le long de l’axe longitudinal de l’HP. Ceci indique le rôle tout particulier de l’hippocampe antérieur dans le mécanisme d’action de l’ECT.
Dans la seconde partie de mon projet, j’ai tenté d’adresser certains biais potentiels dans les études actuelle d’anatomie computationnelle qui limitent l’interprétation neurobiologique des changements de volume observés après un traitement d’ECT. En effet, les contrastes pondérés en T1 sont aussi influencés par les propriétés microstructurelles du tissu cérébral (le contenu en eau, myéline et fer). Par conséquent, nous avons utilisé des acquisitions d’imagerie par résonance magnétique (IRM) avancées dans un nouvel échantillon de 9 patients afin de faire une investigation quantitative de la contribution de la matière grise, de l’eau, de la myéline et du fer à la plasticité qui a lieu lors d’un traitement d’ECT. Nous avons observé une augmentation de la matière grise dans l’HP et le cortex cingulaire antérieur sans changement notable au niveau des propriétés microstructurelles. Nous avons aussi trouvé qu’un large nombre de régions incluant le cortex préfrontal médial, les HP, le striatum ventral et le précuneus était associé avec le changement d’état clinique. Dans le cortex préfrontal médial, il y avait une grande contribution de l’eau et de la myéline sans contribution notable de la matière grise, ce qui signifie que les études morphométriques classiques n’auraient pas détecté cette association. Ceci indique le potentiel de l’IRM quantitatif afin de mieux comprendre les processus associés aux bénéfices thérapeutiques de l’ECT sur la dépression
INVESTIGATING HUMAN WHITE MATTER ORGANIZATION WITH MULTIMODAL QUANTITATIVE MAGNETIC RESONANCE IMAGING
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Effect of 16P11.2 copy number variants on cognitive traits and brain structures
No full textThe 600kb 16p11.2 CNVs (breakpoints 4–5, 29.6-30.2 Mb-Hg19) are among the most frequent genetic risk factors for neurodevelopmental and psychiatric conditions: A 10-fold enrichment of deletions and duplications is observed in autism cohorts and a 10-fold enrichment of duplications in schizophrenia cohorts. Previous studies demonstrated “mirror” effects of both CNVs on body mass index and head circumference (deletion>control>duplication). However, the large global effect of brain size and the sample size of the two previous neuroimaging studies limited the interpretation of the analyses on regional brain structures, any estimate of the effect size, and the generalizability of the results across different ascertainments of the patients.
In the first part of my Ph.D., I analyze structural magnetic resonance imaging (MRI) on 78 deletion carriers, 71 duplication carriers, and 212 controls. I show that both CNVs affect in a “mirror” way the volume and the cortical surface of the insula (Cohen’s d>1), whilst other brain regions are preferentially altered in either the deletion carriers (calcarine cortex and superior, middle, transverse temporal gyri, Cohen’s d>1) or the duplication carriers (caudate and hippocampus, Cohen’s d of 0.5 to 1). Results are generalizable across scanning sites, computational methods, age, sex, ascertainment for psychiatric disorders. They partially overlap with results of meta-analyses performed across psychiatric disorders.
In the second part, I characterize the developmental trajectory of global brain metrics and regional brain structures in the 16p11.2 CNV carriers. I adapt a previously published longitudinal pipeline and normalizing method, derived from 339 typically developing individuals aged from 4.5 to 20 years old. From this population of reference, I Z-score our cross-sectional 16p11.2 dataset and show that all the brain alterations in the 16p11.2 carriers are already present at 4.5 years old and follow parallel trajectories to the controls.
In summary, my results suggest that brain alterations, present in childhood and stable across adolescence and adulthood, are related to the risk conferred by the 16p11.2 CNVs, regardless of the carriers’ symptoms. Additional factors are therefore likely required for the development of psychiatric disorders. I highlight the relevance of studying genetic risk factors and mechanisms as a complement to groups defined by behavioral criteria. Further studies comparing multiple CNVs and monogenic conditions, from the earliest age, are required to understand the onset of neuroanatomical alterations and their overlap between different genetic risk factors for neurodevelopmental disorders.
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Les variations en nombre de copies (CNV), au locus 16p11.2 et d’une taille d’600kb (points de cassure 4–5, 29.6-30.2 Mb-Hg19) représentent un des facteurs de risque génétique les plus fréquents parmi les troubles psychiatriques : 10% d’enrichissement en délétion et duplication pour les troubles du spectre autistique, 10% d’enrichissement en duplication pour la schizophrénie. Les effets « miroirs » des deux CNVs sur l’indice de masse corporelle et le périmètre cranien ont déjà été démontrés (délétion>contrôle>duplication). Cependant, les différences en taille de cerveau et les échantillons des deux précédentes études de neuro- imagerie ont limité les analyses des régions cérébrales, l’estimation de la taille des effets, et la généralisation des résultats selon les modes de recrutement des patients.
Dans cette thèse, j’analyse les images par résonance magnétique (IRM) de 78 porteurs de la délétion, 71 porteurs de la duplication et 212 participants contrôles. Je montre que les deux CNVs sont associées à des différences « en miroir » du volume et de la surface corticale de l’insula (Cohen’s d>1), tandis que le cortex calcarin, les gyri temporaux supérieur, moyen et transverse sont préférentiellement altérés par la délétion (Cohen’s d>1), les noyaux caudés et l’hippocampe sont préférentiellement altérés par la duplication (0.5<Cohen’s d<1). Les résultats sont généralisables à travers les differents sites d’IRM, les méthodes d’analyse computationnelle, les âges, les sexes et les divers diagnostiques psychiatriques des patients. Les résultats chevauchent partiellement ceux d’une méta-analyse sur plusieurs diagnostiques psychiatriques. Dans un second temps, je caractérise la trajectoire développementale de ces différences cérébrales. J’adapte un pipeline longitunal et une méthode de normalisation déjà publiés, construits à partir de 339 participants contrôles de 4.5 à 20 ans. Je calcule des Z-scores pour nos données transversales et montre que les différences cérébrales liées aux CNVs sont déjà présentes à 4.5 ans, avec les mêmes tailles d’effet et une trajectoire parallèle aux contrôles. En résumé, mes résultats suggèrent que les différences cérébrales, présentes dans la jeune enfance et stables à l’adolescence et l’âge adulte, sont liées au risque conféré par les CNVs en 16p11.2, quelque soient les symptômes. Des facteurs additionnels sont probablement nécessaires pour le développement de maladies psychiatriques. Je montre la pertinence d’étudier les facteurs de risque génétiques en complément des groupes de patients définis sur des critères comportementaux. Des études comparant diverses conditions génétiques, dès la naissance, sont nécessaires pour comprendre le début et le chevauchement des différences neuro-anatomiques observées pour différents facteurs de risque génétiques
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