RESUMO
Connectome spectrum electromagnetic tomography (CSET) combines diffusion MRI-derived structural connectivity data with well-established graph signal processing tools to solve the M/EEG inverse problem. Using simulated EEG signals from fMRI responses, and two EEG datasets on visual-evoked potentials, we provide evidence supporting that (i) CSET captures realistic neurophysiological patterns with better accuracy than state-of-the-art methods, (ii) CSET can reconstruct brain responses more accurately and with more robustness to intrinsic noise in the EEG signal. These results demonstrate that CSET offers high spatio-temporal accuracy, enabling neuroscientists to extend their research beyond the current limitations of low sampling frequency in functional MRI and the poor spatial resolution of M/EEG.
Assuntos
Conectoma , Humanos , Conectoma/métodos , Eletroencefalografia/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Imageamento por Ressonância Magnética/métodos , Fenômenos EletromagnéticosRESUMO
Structural connectivity in the brain is typically studied by reducing its observation to a single spatial resolution. However, the brain possesses a rich architecture organized over multiple scales linked to one another. We explored the multiscale organization of human connectomes using datasets of healthy subjects reconstructed at five different resolutions. We found that the structure of the human brain remains self-similar when the resolution of observation is progressively decreased by hierarchical coarse-graining of the anatomical regions. Strikingly, a geometric network model, where distances are not Euclidean, predicts the multiscale properties of connectomes, including self-similarity. The model relies on the application of a geometric renormalization protocol which decreases the resolution by coarse-graining and averaging over short similarity distances. Our results suggest that simple organizing principles underlie the multiscale architecture of human structural brain networks, where the same connectivity law dictates short- and long-range connections between different brain regions over many resolutions. The implications are varied and can be substantial for fundamental debates, such as whether the brain is working near a critical point, as well as for applications including advanced tools to simplify the digital reconstruction and simulation of the brain.
Assuntos
Encéfalo/fisiologia , Conectoma , Modelos Neurológicos , Vias Neurais , Humanos , Modelos Estatísticos , Rede NervosaRESUMO
Functional magnetic resonance imaging (fMRI) is a non-invasive technique that facilitates the study of brain activity by measuring changes in blood flow. Brain activity signals can be recorded during the alternate performance of given tasks, that is, task fMRI (tfMRI), or during resting-state, that is, resting-state fMRI (rsfMRI), as a measure of baseline brain activity. This contributes to the understanding of how the human brain is organized in functionally distinct subdivisions. fMRI experiments from high-resolution scans provide hundred of thousands of longitudinal signals for each individual, corresponding to brain activity measurements over each voxel of the brain along the duration of the experiment. In this context, we propose novel visualization techniques for high-dimensional functional data relying on depth-based notions that enable computationally efficient 2-dim representations of fMRI data, which elucidate sample composition, outlier presence, and individual variability. We believe that this previous step is crucial to any inferential approach willing to identify neuroscientific patterns across individuals, tasks, and brain regions. We present the proposed technique via an extensive simulation study, and demonstrate its application on a motor and language tfMRI experiment.
Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Humanos , IdiomaRESUMO
The structural complexity of the thalamus, due to its mixed composition of gray and white matter, make it challenging to disjoint and quantify each tissue contribution to the thalamic anatomy. This work promotes the use of partial-volume-based over probabilistic-based tissue segmentation approaches to better capture thalamic gray matter differences between patients at different stages of psychosis (early and chronic) and healthy controls. The study was performed on a cohort of 23 patients with schizophrenia, 41 with early psychosis and 69 age and sex-matched healthy subjects. Six tissue segmentation approaches were employed to obtain the gray matter concentration/probability images. The statistical tests were applied at three different anatomical scales: whole thalamus, thalamic subregions and voxel-wise. The results suggest that the partial volume model estimation of gray matter is more sensitive to detect atrophies within the thalamus of patients with psychosis. However all the methods detected gray matter deficit in the pulvinar, particularly in early stages of psychosis. This study demonstrates also that the gray matter decrease varies nonlinearly with age and between nuclei. While a gray matter loss was found in the pulvinar of patients in both stages of psychosis, reduced gray matter in the mediodorsal was only observed in early psychosis subjects. Finally, our analyses point to alterations in a sub-region comprising the lateral posterior and ventral posterior nuclei. The obtained results reinforce the hypothesis that thalamic gray matter assessment is more reliable when the tissues segmentation method takes into account the partial volume effect.
Assuntos
Substância Cinzenta/patologia , Interpretação de Imagem Assistida por Computador/métodos , Neuroimagem/métodos , Transtornos Psicóticos/patologia , Esquizofrenia/patologia , Núcleos Talâmicos/patologia , Adulto , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Transtornos Psicóticos/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Núcleos Talâmicos/diagnóstico por imagem , Fatores de Tempo , Adulto JovemRESUMO
Spherical deconvolution methods are widely used to estimate the brain's white-matter fiber orientations from diffusion MRI data. In this study, eight spherical deconvolution algorithms were implemented and evaluated. These included two model selection techniques based on the extended Bayesian information criterion (i.e., best subset selection and the least absolute shrinkage and selection operator), iteratively reweighted l2- and l1-norm approaches to approximate the l0-norm, sparse Bayesian learning, Cauchy deconvolution, and two accelerated Richardson-Lucy algorithms. Results from our exhaustive evaluation show that there is no single optimal method for all different fiber configurations, suggesting that further studies should be conducted to find the optimal way of combining solutions from different methods. We found l0-norm regularization algorithms to resolve more accurately fiber crossings with small inter-fiber angles. However, in voxels with very dominant fibers, algorithms promoting more sparsity are less accurate in detecting smaller fibers. In most cases, the best algorithm to reconstruct fiber crossings with two fibers did not perform optimally in voxels with one or three fibers. Therefore, simplified validation systems as employed in a number of previous studies, where only two fibers with similar volume fractions were tested, should be avoided as they provide incomplete information. Future studies proposing new reconstruction methods based on high angular resolution diffusion imaging data should validate their results by considering, at least, voxels with one, two, and three fibers, as well as voxels with dominant fibers and different diffusion anisotropies.
Assuntos
Algoritmos , Encéfalo/anatomia & histologia , Imagem de Difusão por Ressonância Magnética/métodos , Substância Branca/anatomia & histologia , Teorema de Bayes , Imagem de Tensor de Difusão/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , Inquéritos e QuestionáriosRESUMO
Autism spectrum disorders (ASD) and early-onset psychosis (EOP) are neurodevelopmental disorders that share genetic, clinical and cognitive facets; it is unclear if these disorders also share spatially overlapping cortical thickness (CT) and surface area (SA) abnormalities. MRI scans of 30 ASD, 29 patients with early-onset first-episode psychosis (EO-FEP) and 26 typically developing controls (TD) (age range 10-18 years) were analyzed by the FreeSurfer suite to calculate vertex-wise estimates of CT, SA, and cortical volume. Two publicly available datasets of ASD and EOP (age range 7-18 years and 5-17 years, respectively) were used for replication analysis. ASD and EO-FEP had spatially overlapping areas of cortical thinning and reduced SA in the bilateral insula (all p's < .00002); 37% of all left insular vertices presenting with significant cortical thinning and 20% (left insula) and 61% (right insula) of insular vertices displaying decreased SA overlapped across both disorders. In both disorders, SA deficits contributed more to cortical volume decreases than reductions in CT did. This finding, as well as the novel finding of an absence of spatial overlap (for ASD) or marginal overlap (for EOP) of deficits in CT and SA, was replicated in the two nonoverlapping independent samples. The insula appears to be a region with transdiagnostic vulnerability for deficits in CT and SA. The finding of nonexistent or small spatial overlap between CT and SA deficits in young people with ASD and psychosis may point to the involvement of common aberrant early neurodevelopmental mechanisms in their pathophysiology.
Assuntos
Transtorno do Espectro Autista/patologia , Transtornos Psicóticos/patologia , Adolescente , Envelhecimento/patologia , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno do Espectro Autista/psicologia , Mapeamento Encefálico , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Criança , Cognição , Bases de Dados Factuais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/psicologiaRESUMO
Mapping the impact of pregnancy on the human brain is essential for understanding the neurobiology of maternal caregiving. Recently, we found that pregnancy leads to a long-lasting reduction in cerebral gray matter volume. However, the morphometric features behind the volumetric reductions remain unexplored. Furthermore, the similarity between these reductions and those occurring during adolescence, another hormonally similar transitional period of life, still needs to be investigated. Here, we used surface-based methods to analyze the longitudinal magnetic resonance imaging data of a group of 25 first-time mothers (before and after pregnancy) and compare them to those of a group of 25 female adolescents (during 2 years of pubertal development). For both first-time mothers and adolescent girls, a monthly rate of volumetric reductions of 0.09 mm3 was observed. In both cases, these reductions were accompanied by decreases in cortical thickness, surface area, local gyrification index, sulcal depth, and sulcal length, as well as increases in sulcal width. In fact, the changes associated with pregnancy did not differ from those that characterize the transition during adolescence in any of these measures. Our findings are consistent with the notion that the brain morphometric changes associated with pregnancy and adolescence reflect similar hormonally primed biological processes.
Assuntos
Adaptação Fisiológica/fisiologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/crescimento & desenvolvimento , Imageamento por Ressonância Magnética/tendências , Gravidez/fisiologia , Adolescente , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Tamanho do Órgão/fisiologia , Adulto JovemRESUMO
BACKGROUND: There is increasing evidence that redox dysregulation, which can lead to oxidative stress and eventually to impairment of oligodendrocytes and parvalbumin interneurons, may underlie brain connectivity alterations in schizophrenia. Accordingly, we previously reported that levels of brain antioxidant glutathione in the medial prefrontal cortex were positively correlated with increased functional connectivity along the cingulum bundle in healthy controls but not in early psychosis patients. In a recent randomized controlled trial, we observed that 6-month supplementation with a glutathione precursor, N-acetyl-cysteine, increased brain glutathione levels and improved symptomatic expression and processing speed. METHODS: We investigated the effect of N-acetyl-cysteine supplementation on the functional connectivity between regions of the cingulate cortex, which have been linked to positive symptoms and processing speed decline. In this pilot study, we compared structural connectivity and resting-state functional connectivity between early psychosis patients treated with 6-month N-acetyl-cysteine (n = 9) or placebo (n = 11) supplementation with sex- and age-matched healthy control subjects (n = 74). RESULTS: We observed that 6-month N-acetyl-cysteine supplementation increases functional connectivity along the cingulum and more precisely between the caudal anterior part and the isthmus of the cingulate cortex. These functional changes can be partially explained by an increase of centrality of these regions in the functional brain network. CONCLUSIONS: N-acetyl-cysteine supplementation has a positive effect on functional connectivity within the cingulate cortex in early psychosis patients. To our knowledge, this is the first study suggesting that increased brain glutathione levels via N-acetyl-cysteine supplementation may improve brain functional connectivity.
Assuntos
Acetilcisteína/uso terapêutico , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Giro do Cíngulo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transtornos Psicóticos/tratamento farmacológico , Acetilcisteína/efeitos adversos , Adulto , Antioxidantes/efeitos adversos , Mapeamento Encefálico/métodos , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Europa (Continente) , Feminino , Glutationa/metabolismo , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Projetos Piloto , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/metabolismo , Transtornos Psicóticos/psicologia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Global structural brain connectivity has been reported to be sex-dependent with women having increased interhemispheric connectivity (InterHc) and men having greater intrahemispheric connectivity (IntraHc). However, (a) smaller brains show greater InterHc, (b) larger brains show greater IntraHc, and (c) women have, on average, smaller brains than men. Therefore, sex differences in brain size may modulate sex differences in global brain connectivity. At the behavioural level, sex-dependent differences in connectivity are thought to contribute to men-women differences in spatial and verbal abilities. But this has never been tested at the individual level. The current study assessed whether individual differences in global structural connectome measures (InterHc, IntraHc and the ratio of InterHc relative to IntraHc) predict spatial and verbal ability while accounting for the effect of sex and brain size. The sample included forty men and forty women, who did neither differ in age nor in verbal and spatial latent components defined by a broad battery of tests and tasks. High-resolution T1-weighted and diffusion-weighted images were obtained for computing brain size and reconstructing the structural connectome. Results showed that men had higher IntraHc than women, while women had an increased ratio InterHc/IntraHc. However, these sex differences were modulated by brain size. Increased InterHc relative to IntraHc predicted higher spatial and verbal ability irrespective of sex and brain size. The positive correlations between the ratio InterHc/IntraHc and the spatial and verbal abilities were confirmed in 1000 random samples generated by bootstrapping. Therefore, sex differences in global structural connectome connectivity were modulated by brain size and did not underlie sex differences in verbal and spatial abilities. Rather, the level of dominance of InterHc over IntraHc may be associated with individual differences in verbal and spatial abilities in both men and women.
Assuntos
Encéfalo/anatomia & histologia , Cognição/fisiologia , Vias Neurais/anatomia & histologia , Caracteres Sexuais , Adolescente , Adulto , Encéfalo/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/fisiologia , Tamanho do Órgão , Adulto JovemRESUMO
Executive function (EF) performance is associated with measurements of white matter microstructure (WMS) in typical individuals. Impaired EF is a hallmark symptom of autism spectrum disorders (ASD) but it is unclear how impaired EF relates to variability in WMS. Twenty-one male youth (8-18 years) with ASD and without intellectual disability and twenty-one typical male participants (TP) matched for age, intelligence quotient, handedness, race and parental socioeconomic status were recruited. Five EF domains were assessed and several DTI-based measurements of WMS [fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD)] were estimated for eighteen white matter tracts. The ASD group had lower scores for attention (F = 8.37, p = 0.006) and response inhibition (F = 13.09, p = 0.001). Age-dependent changes of EF performance and WMS measurements were present in TP but attenuated in the ASD group. The strongest diagnosis-by-age effect was found for forceps minor, left anterior thalamic radiation and left cingulum angular bundle (all p's ≤ 0.002). In these tracts subjects with ASD tended to have equal or increased FA and/or reduced MD and/or RD at younger ages while controls had increased FA and/or reduced MD and/or RD thereafter. Only for TP individuals, increased FA in the left anterior thalamic radiation was associated with better response inhibition, while reduced RD in forceps minor and left cingulum angular bundle was related to better problem solving and working memory performance respectively. These findings provide novel insight into the age-dependency of EF performance and WMS in ASD, which can be instructive to cognitive training programs.
Assuntos
Transtorno do Espectro Autista/fisiopatologia , Encéfalo/patologia , Função Executiva/fisiologia , Substância Branca/fisiopatologia , Adolescente , Fatores Etários , Criança , Feminino , Humanos , MasculinoRESUMO
Math-gifted subjects are characterized by above-age performance in intelligence tests, exceptional creativity, and high task commitment. Neuroimaging studies reveal enhanced functional brain organization and white matter microstructure in the frontoparietal executive network of math-gifted individuals. However, the cortical morphometry of these subjects remains largely unknown. The main goal of this study was to compare the cortical morphometry of math-gifted adolescents with that of an age- and IQ-matched control group. We used surface-based methods to perform a vertex-wise analysis of cortical thickness and surface area. Our results show that math-gifted adolescents present a thinner cortex and a larger surface area in key regions of the frontoparietal and default mode networks, which are involved in executive processing and creative thinking, respectively. The combination of reduced cortical thickness and larger surface area suggests above-age neural maturation of these networks in math-gifted individuals. Hum Brain Mapp 37:1893-1902, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Criança Superdotada , Lobo Frontal/diagnóstico por imagem , Matemática , Modelos Neurológicos , Lobo Parietal/diagnóstico por imagem , Adolescente , Mapeamento Encefálico , Criança , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Testes de Inteligência , Imageamento por Ressonância Magnética , Masculino , Estatísticas não ParamétricasRESUMO
The human cerebral cortex appears to shrink during adolescence. To delineate the dynamic morphological changes involved in this process, 52 healthy male and female adolescents (11-17 years old) were neuroimaged twice using magnetic resonance imaging, approximately 2 years apart. Using a novel morphometric analysis procedure combining the FreeSurfer and BrainVisa image software suites, we quantified global and lobar change in cortical thickness, outer surface area, the gyrification index, the average Euclidean distance between opposing sides of the white matter surface (gyral white matter thickness), the convex ("exposed") part of the outer cortical surface (hull surface area), sulcal length, depth, and width. We found that the cortical surface flattens during adolescence. Flattening was strongest in the frontal and occipital cortices, in which significant sulcal widening and decreased sulcal depth co-occurred. Globally, sulcal widening was associated with cortical thinning and, for the frontal cortex, with loss of surface area. For the other cortical lobes, thinning was related to gyral white matter expansion. The overall flattening of the macrostructural three-dimensional architecture of the human cortex during adolescence thus involves changes in gray matter and effects of the maturation of white matter.
Assuntos
Mapeamento Encefálico , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/crescimento & desenvolvimento , Adolescente , Fatores Etários , Criança , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Modelos NeurológicosRESUMO
Recent functional neuroimaging studies have shown differences in brain activation between mathematically gifted adolescents and controls. The aim of this study was to investigate the relationship between mathematical giftedness, intelligent quotient (IQ), and the microstructure of white matter tracts in a sample composed of math-gifted adolescents and aged-matched controls. Math-gifted subjects were selected through a national program based on detecting enhanced visuospatial abilities and creative thinking. We used diffusion tensor imaging to assess white matter microstructure in neuroanatomical connectivity. The processing included voxel-wise and region of interest-based analyses of the fractional anisotropy (FA), a parameter which is purportedly related to white matter microstructure. In a whole-sample analysis, IQ showed a significant positive correlation with FA, mainly in the corpus callosum, supporting the idea that efficient information transfer between hemispheres is crucial for higher intellectual capabilities. In addition, math-gifted adolescents showed increased FA (adjusted for IQ) in white matter tracts connecting frontal lobes with basal ganglia and parietal regions. The enhanced anatomical connectivity observed in the forceps minor and splenium may underlie the greater fluid reasoning, visuospatial working memory, and creative capabilities of these children.
Assuntos
Encéfalo/anatomia & histologia , Criança Superdotada , Inteligência , Matemática , Substância Branca/anatomia & histologia , Adolescente , Anisotropia , Criança , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Testes de Inteligência , Masculino , Fibras Nervosas Mielinizadas , Vias Neurais/anatomia & histologiaRESUMO
BACKGROUND: ECG-gated cardiac CT is now widely used in infants with congenital heart disease (CHD). Deep Learning Image Reconstruction (DLIR) could improve image quality while minimizing the radiation dose. OBJECTIVES: To define the potential dose reduction using DLIR with an anthropomorphic phantom. METHOD: An anthropomorphic pediatric phantom was scanned with an ECG-gated cardiac CT at four dose levels. Images were reconstructed with an iterative and a deep-learning reconstruction algorithm (ASIR-V and DLIR). Detectability of high-contrast vessels were computed using a mathematical observer. Discrimination between two vessels was assessed by measuring the CT spatial resolution. The potential dose reduction while keeping a similar level of image quality was assessed. RESULTS: DLIR-H enhances detectability by 2.4% and discrimination performances by 20.9% in comparison with ASIR-V 50. To maintain a similar level of detection, the dose could be reduced by 64% using high-strength DLIR in comparison with ASIR-V50. CONCLUSION: DLIR offers the potential for a substantial dose reduction while preserving image quality compared to ASIR-V.
Assuntos
Técnicas de Imagem de Sincronização Cardíaca , Aprendizado Profundo , Cardiopatias Congênitas , Imagens de Fantasmas , Valor Preditivo dos Testes , Doses de Radiação , Exposição à Radiação , Interpretação de Imagem Radiográfica Assistida por Computador , Humanos , Lactente , Exposição à Radiação/prevenção & controle , Cardiopatias Congênitas/diagnóstico por imagem , Reprodutibilidade dos Testes , Eletrocardiografia , Angiografia Coronária/métodos , Angiografia por Tomografia Computadorizada , Fatores EtáriosRESUMO
Across development, experience has a strong impact on the way we think and adapt. School experience affects academic and social-emotional outcomes, yet whether differences in pedagogical experience modulate underlying brain network development is still unknown. In this study, we compared the brain network dynamics of students with different pedagogical backgrounds. Specifically, we characterized the diversity and stability of brain activity at rest by combining both resting-state fMRI and diffusion-weighted structural imaging data of 87 4-18 years old students experiencing either the Montessori pedagogy (i.e., student-led, trial-and-error pedagogy) or the traditional pedagogy (i.e., teacher-led, test-based pedagogy). Our results revealed spatiotemporal brain dynamics differences between students as a function of schooling experience at the whole-brain level. Students from Montessori schools showed overall higher functional integration (higher system diversity) and neural stability (lower spatiotemporal diversity) compared to traditionally schooled students. Higher integration was explained mainly through the cerebellar (CBL) functional network. In contrast, higher temporal stability was observed in the ventral attention, dorsal attention, somatomotor, frontoparietal, and CBL functional networks. This study suggests a form of experience-dependent dynamic functional connectivity plasticity, in learning-related networks.
RESUMO
Increasing evidence points toward the role of the extracellular matrix, specifically matrix metalloproteinase 9 (MMP-9), in the pathophysiology of psychosis. MMP-9 is a critical regulator of the crosstalk between peripheral and central inflammation, extracellular matrix remodeling, hippocampal development, synaptic pruning, and neuroplasticity. Here, we aim to characterize the relationship between plasma MMP-9 activity, hippocampal microstructure, and cognition in healthy individuals and individuals with early phase psychosis. We collected clinical, blood, and structural and diffusion-weighted magnetic resonance imaging data from 39 individuals with early phase psychosis and 44 age and sex-matched healthy individuals. We measured MMP-9 plasma activity, hippocampal extracellular free water (FW) levels, and hippocampal volumes. We used regression analyses to compare MMP-9 activity, hippocampal FW, and volumes between groups. We then examined associations between MMP-9 activity, FW levels, hippocampal volumes, and cognitive performance assessed with the MATRICS battery. All analyses were controlled for age, sex, body mass index, cigarette smoking, and years of education. Individuals with early phase psychosis demonstrated higher MMP-9 activity (p < 0.0002), higher left (p < 0.05) and right (p < 0.05) hippocampal FW levels, and lower left (p < 0.05) and right (p < 0.05) hippocampal volume than healthy individuals. MMP-9 activity correlated positively with hippocampal FW levels (all participants and individuals with early phase psychosis) and negatively with hippocampal volumes (all participants and healthy individuals). Higher MMP-9 activity and higher hippocampal FW levels were associated with slower processing speed and worse working memory performance in all participants. Our findings show an association between MMP-9 activity and hippocampal microstructural alterations in psychosis and an association between MMP-9 activity and cognitive performance. Further, more extensive longitudinal studies should examine the therapeutic potential of MMP-9 modulators in psychosis.
Assuntos
Hipocampo , Metaloproteinase 9 da Matriz , Transtornos Psicóticos , Humanos , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/metabolismo , Masculino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Feminino , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/patologia , Transtornos Psicóticos/fisiopatologia , Adulto , Adulto Jovem , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/patologia , Imagem de Difusão por Ressonância Magnética , Imageamento por Ressonância MagnéticaRESUMO
Given the unpredictable rapid onset and ubiquitous consequences of weight gain induced by antipsychotics, there is a pressing need to get insights into the underlying processes at the brain system level that will allow stratification of "at risk" patients. The pathophysiological hypothesis at hand is focused on brain networks governing impulsivity that are modulated by neuro-inflammatory processes. To this aim, we investigated brain anatomy and functional connectivity in patients with early psychosis (median age: 23 years, IQR = 21-27) using anthropometric data and magnetic resonance imaging acquired one month to one year after initiation of AP medication. Our analyses included 19 patients with high and rapid weight gain (i.e., ≥5% from baseline weight after one month) and 23 patients with low weight gain (i.e., <5% from baseline weight after one month). We replicated our analyses in young (26 years, IQR = 22-33, N = 102) and middle-aged (56 years, IQR = 51-62, N = 875) healthy individuals from the general population. In early psychosis patients, higher weight gain was associated with poor impulse control score (ß = 1.35; P = 0.03). Here, the observed brain differences comprised nodes of impulsivity networks - reduced frontal lobe grey matter volume (Pcorrected = 0.007) and higher striatal volume (Pcorrected = 0.048) paralleled by disruption of fronto-striatal functional connectivity (R = -0.32; P = 0.04). Weight gain was associated with the inflammatory biomarker plasminogen activator inhibitor-1 (ß = 4.9, P = 0.002). There was no significant association between increased BMI or weight gain and brain anatomy characteristics in both cohorts of young and middle-aged healthy individuals. Our findings support the notion of weight gain in treated psychotic patients associated with poor impulse control, impulsivity-related brain networks and chronic inflammation.
Assuntos
Antipsicóticos , Transtornos Psicóticos , Pessoa de Meia-Idade , Humanos , Adulto Jovem , Adulto , Antipsicóticos/uso terapêutico , Encéfalo , Comportamento Impulsivo/fisiologia , Aumento de Peso , Imageamento por Ressonância Magnética/métodosRESUMO
Adolescence is marked by the maturation of systems involved in emotional regulation and by an increased risk for internalizing disorders (anxiety/depression), especially in females. Hypothalamic-pituitary-adrenal (HPA)-axis function and redox homeostasis (balance between reactive oxygen species and antioxidants) have both been associated with internalizing disorders and may represent critical factors for the development of brain networks of emotional regulation. However, sex-specific interactions between these factors and internalizing symptoms and their link with brain maturation remain unexplored. We investigated in a cohort of adolescents aged 13-15 from the general population (n = 69) whether sex-differences in internalizing symptoms were associated with the glutathione (GSH)-redox cycle homeostasis and HPA-axis function and if these parameters were associated with brain white matter microstructure development. Female adolescents displayed higher levels of internalizing symptoms, GSH-peroxidase (GPx) activity and cortisol/11-deoxycortisol ratio than males. There was a strong correlation between GPx and GSH-reductase (Gred) activities in females only. The cortisol/11-deoxycortisol ratio, related to the HPA-axis activity, was associated with internalizing symptoms in both sexes, whereas GPx activity was associated with internalizing symptoms in females specifically. The cortisol/11-deoxycortisol ratio mediated sex-differences in internalizing symptoms and the association between anxiety and GPx activity in females specifically. In females, GPx activity was positively associated with generalized fractional anisotropy in widespread white matter brain regions. We found that higher levels of internalizing symptoms in female adolescents than in males relate to sex-differences in HPA-axis function. In females, our results suggest an important interplay between HPA-axis function and GSH-homeostasis, a parameter strongly associated with brain white matter microstructure.
Assuntos
Hidrocortisona , Substância Branca , Humanos , Masculino , Adolescente , Feminino , Substância Branca/diagnóstico por imagem , Cortodoxona , Encéfalo/diagnóstico por imagem , Oxirredução , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Antioxidantes , Estresse PsicológicoRESUMO
Wavelet-based methods have been developed for statistical analysis of functional MRI and PET data, where the wavelet transformation is employed as a tool for efficient signal representation. A number of studies using these approaches have reported better estimation capabilities, in terms of increased sensitivity and specificity, than the standard statistical analyses in the spatial domain. In line with these previous studies, the present report proposes a statistical analysis in the wavelet domain for the estimation of inter-group differences from structural MRI data. The procedure, called wavelet-based morphometry (WBM), was implemented under a voxel-based morphometry (VBM) style analysis. It was evaluated by comparing the gray-matter images of a group of 32 healthy subjects whose images were artificially altered to induce thinning of the cortex, with a different group of 32 healthy subjects whose images were unaltered. In order to quantify the performance of the reconstruction from a practical perspective, the same comparison was also conducted with standard VBM using SPM's Gaussian random fields and FSL's cluster-based statistics, family-wise error corrected, for datasets spatially-normalized via two different registration methods (i.e., SyN and FNIRT). The effect of using different amounts of smoothing, Battle-Lemarié filters and resolution levels in the wavelet transform was also investigated. Results support the proposed approach as a different and promising methodology to assess the structural morphometric differences between different populations of subjects.
Assuntos
Algoritmos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Brain aneurysm detection in Time-Of-Flight Magnetic Resonance Angiography (TOF-MRA) has undergone drastic improvements with the advent of Deep Learning (DL). However, performances of supervised DL models heavily rely on the quantity of labeled samples, which are extremely costly to obtain. Here, we present a DL model for aneurysm detection that overcomes the issue with "weak" labels: oversized annotations which are considerably faster to create. Our weak labels resulted to be four times faster to generate than their voxel-wise counterparts. In addition, our model leverages prior anatomical knowledge by focusing only on plausible locations for aneurysm occurrence. We first train and evaluate our model through cross-validation on an in-house TOF-MRA dataset comprising 284 subjects (170 females / 127 healthy controls / 157 patients with 198 aneurysms). On this dataset, our best model achieved a sensitivity of 83%, with False Positive (FP) rate of 0.8 per patient. To assess model generalizability, we then participated in a challenge for aneurysm detection with TOF-MRA data (93 patients, 20 controls, 125 aneurysms). On the public challenge, sensitivity was 68% (FP rate = 2.5), ranking 4th/18 on the open leaderboard. We found no significant difference in sensitivity between aneurysm risk-of-rupture groups (p = 0.75), locations (p = 0.72), or sizes (p = 0.15). Data, code and model weights are released under permissive licenses. We demonstrate that weak labels and anatomical knowledge can alleviate the necessity for prohibitively expensive voxel-wise annotations.