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PURPOSE: This study investigated the association between childhood eating behaviors and cortical morphology, in relation to sex and age, in a community sample. METHODS: Neuroimaging data of 71 children (mean age = 9.9 ± 1.4 years; 39 boys/32 girls) were obtained from the Nathan Kline Institute-Rockland Sample. Emotional overeating, food fussiness, and emotional undereating were assessed using the Children's Eating Behavior Questionnaire. Cortical thickness was obtained at 81,924 vertices covering the entire cortex. Generalized Linear Mixed Models were used for statistical analysis. RESULTS: There was a significant effect of sex in the association between cortical thickness and emotional overeating (localized at the right postcentral and bilateral superior parietal gyri). Boys with more emotional overeating presented cortical thickening, whereas the opposite was observed in girls (p < 0.05). Different patterns of association were identified between food fussiness and cortical thickness (p < 0.05). The left rostral middle frontal gyrus displayed a positive correlation with food fussiness from 6 to 8 years, but a negative correlation from 12 to 14 years. Emotional undereating was associated with cortical thickening at the left precuneus, left middle temporal gyrus, and left insula (p < 0.05) with no effect of sex or age. CONCLUSIONS: Leveraging on a community sample, findings support distinct patterns of associations between eating behaviors and cortical thickness, depending on sex and age.
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Córtex Cerebral , Comportamento Alimentar , Transtornos da Alimentação e da Ingestão de Alimentos , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Criança , Comportamento Alimentar/psicologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Adolescente , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Fatores Etários , Fatores Sexuais , Emoções/fisiologia , Comportamento Infantil/psicologiaRESUMO
Cortical arealization arises during neurodevelopment from the confluence of molecular gradients representing patterned expression of morphogens and transcription factors. However, whether similar gradients are maintained in the adult brain remains unknown. Here, we uncover three axes of topographic variation in gene expression in the adult human brain that specifically capture previously identified rostral-caudal, dorsal-ventral, and medial-lateral axes of early developmental patterning. The interaction of these spatiomolecular gradients i) accurately reconstructs the position of brain tissue samples, ii) delineates known functional territories, and iii) can model the topographical variation of diverse cortical features. The spatiomolecular gradients are distinct from canonical cortical axes differentiating the primary sensory cortex from the association cortex, but radiate in parallel with the axes traversed by local field potentials along the cortex. We replicate all three molecular gradients in three independent human datasets as well as two nonhuman primate datasets and find that each gradient shows a distinct developmental trajectory across the lifespan. The gradients are composed of several well-known transcription factors (e.g., PAX6 and SIX3), and a small set of genes shared across gradients are strongly enriched for multiple diseases. Together, these results provide insight into the developmental sculpting of functionally distinct brain regions, governed by three robust transcriptomic axes embedded within brain parenchyma.
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Encéfalo , Humanos , Encéfalo/metabolismo , Animais , Adulto , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Fator de Transcrição PAX6/metabolismo , Fator de Transcrição PAX6/genética , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Padronização Corporal/genética , Feminino , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genéticaRESUMO
Recent studies have shown that white-gray contrast (WGC) of either cortical or subcortical gray matter provides for accurate predictions of age in typically developing (TD) children, and that, at least for the cortex, it changes differently with age in subjects with autism spectrum disorder (ASD) compared to their TD peers. Our previous study showed different patterns of contrast change between ASD and TD in sensorimotor and association cortices. While that study was confined to the cortex, we hypothesized that subcortical structures, particularly the thalamus, were involved in the observed cortical dichotomy between lower and higher processing. The current paper investigates that hypothesis using the WGC measures from the thalamus in addition to those from the cortex. We compared age-related WGC changes in the thalamus to those in the cortex. To capture the simultaneity of this change across the two structures, we devised a metric capturing the co-development of the thalamus and cortex (CoDevTC), proportional to the magnitude of cortical and thalamic age-related WGC change. We calculated this metric for each of the subjects in a large homogeneous sample taken from the Autism Brain Imaging Data Exchange (ABIDE) (N = 434). We used structural MRI data from the largest high-quality cross-sectional sample (NYU) as well as two other large high-quality sites, GU and OHSU, all three using Siemens 3T scanners. We observed that the co-development features in ASD and TD exhibit contrasting patterns; specifically, some higher-order thalamic nuclei, such as the lateral dorsal nucleus, exhibited reduction in codevelopment with most of the cortex in ASD compared to TD. Moreover, this difference in the CoDevTC pattern correlates with a number of behavioral measures across multiple cognitive and physiological domains. The results support previous notions of altered connectivity in autism, but add more specific evidence about the heterogeneity in thalamocortical development that elucidates the mechanisms underlying the clinical features of ASD.
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Transtorno do Espectro Autista , Transtorno Autístico , Criança , Humanos , Estudos Transversais , Tálamo , Imageamento por Ressonância MagnéticaRESUMO
Scientific research communities pursue dual imperatives in implementing strategies to share their data. These communities attempt to maximize the accessibility of biomedical data for downstream research use, in furtherance of open science objectives. Simultaneously, such communities safeguard the interests of research participants through data stewardship measures and the integration of suitable risk disclosures to the informed consent process. The Canadian Open Neuroscience Platform (CONP) convened an Ethics and Governance Committee composed of experts in bioethics, neuroethics, and law to develop holistic policy tools, organizational approaches, and technological supports to align the open governance of data with ethical and legal norms. The CONP has adopted novel platform governance methods that favor full data openness, legitimated through the use of robust deidentification processes and informed consent practices. The experience of the CONP is articulated as a potential template for other open science efforts to further build upon. This experience highlights informed consent guidance, deidentification practices, ethicolegal metadata, platform-level norms, and commercialization and publication policies as the principal pillars of a practicable approach to the governance of open data. The governance approach adopted by the CONP stands as a viable model for the broader neuroscience and open science communities to adopt for sharing data in full open access.
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Pesquisa Biomédica , Humanos , Jardins , Canadá , Consentimento Livre e Esclarecido , Bancos de Espécimes BiológicosRESUMO
The hippocampus is an archicortical structure, consisting of subfields with unique circuits. Understanding its microstructure, as proxied by these subfields, can improve our mechanistic understanding of learning and memory and has clinical potential for several neurological disorders. One prominent issue is how to parcellate, register, or retrieve homologous points between two hippocampi with grossly different morphologies. Here, we present a surface-based registration method that solves this issue in a contrast-agnostic, topology-preserving manner. Specifically, the entire hippocampus is first analytically unfolded, and then samples are registered in 2D unfolded space based on thickness, curvature, and gyrification. We demonstrate this method in seven 3D histology samples and show superior alignment with respect to subfields using this method over more conventional registration approaches.
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Hipocampo , Imageamento por Ressonância Magnética , Imageamento por Ressonância Magnética/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Lobo Temporal , Técnicas HistológicasRESUMO
Neuroimaging research requires sophisticated tools for analyzing complex data, but efficiently leveraging these tools can be a major challenge, especially on large datasets. CBRAIN is a web-based platform designed to simplify the use and accessibility of neuroimaging research tools for large-scale, collaborative studies. In this paper, we describe how CBRAIN's unique features and infrastructure were leveraged to integrate TAPAS PhysIO, an open-source MATLAB toolbox for physiological noise modeling in fMRI data. This case study highlights three key elements of CBRAIN's infrastructure that enable streamlined, multimodal tool integration: a user-friendly GUI, a Brain Imaging Data Structure (BIDS) data-entry schema, and convenient in-browser visualization of results. By incorporating PhysIO into CBRAIN, we achieved significant improvements in the speed, ease of use, and scalability of physiological preprocessing. Researchers now have access to a uniform and intuitive interface for analyzing data, which facilitates remote and collaborative evaluation of results. With these improvements, CBRAIN aims to become an essential open-science tool for integrative neuroimaging research, supporting FAIR principles and enabling efficient workflows for complex analysis pipelines.
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Background: Schizophrenia is widely recognized as a neurodevelopmental disorder. Abnormal cortical development in otherwise typically developing children and adolescents may be revealed using polygenic risk scores for schizophrenia (PRS-SCZ). Methods: We assessed PRS-SCZ and cortical morphometry in typically developing children and adolescents (3-21 years, 46.8% female) using whole-genome genotyping and T1-weighted magnetic resonance imaging (n = 390) from the PING (Pediatric Imaging, Neurocognition, and Genetics) cohort. We contextualized the findings using 1) age-matched transcriptomics, 2) histologically defined cytoarchitectural types and functionally defined networks, and 3) case-control differences of schizophrenia and other major psychiatric disorders derived from meta-analytic data of 6 ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) working groups, including a total of 12,876 patients and 15,670 control participants. Results: Higher PRS-SCZ was associated with greater cortical thickness, which was most prominent in areas with heightened gene expression of dendrites and synapses. PRS-SCZ-related increases in vertexwise cortical thickness were mainly distributed in association cortical areas, particularly the ventral attention network, while relatively sparing koniocortical type cortex (i.e., primary sensory areas). The large-scale pattern of cortical thickness increases related to PRS-SCZ mirrored the pattern of cortical thinning in schizophrenia and mood-related psychiatric disorders derived from the ENIGMA consortium. Age group models illustrate a possible trajectory from PRS-SCZ-associated cortical thickness increases in early childhood toward thinning in late adolescence, with the latter resembling the adult brain phenotype of schizophrenia. Conclusions: Collectively, combining imaging genetics with multiscale mapping, our work provides novel insight into how genetic risk for schizophrenia affects the cortex early in life.
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The Canadian Open Neuroscience Platform (CONP) takes a multifaceted approach to enabling open neuroscience, aiming to make research, data, and tools accessible to everyone, with the ultimate objective of accelerating discovery. Its core infrastructure is the CONP Portal, a repository with a decentralized design, where datasets and analysis tools across disparate platforms can be browsed, searched, accessed, and shared in accordance with FAIR principles. Another key piece of CONP infrastructure is NeuroLibre, a preprint server capable of creating and hosting executable and fully reproducible scientific publications that embed text, figures, and code. As part of its holistic approach, the CONP has also constructed frameworks and guidance for ethics and data governance, provided support and developed resources to help train the next generation of neuroscientists, and has fostered and grown an engaged community through outreach and communications. In this manuscript, we provide a high-level overview of this multipronged platform and its vision of lowering the barriers to the practice of open neuroscience and yielding the associated benefits for both individual researchers and the wider community.
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Neurociências , Canadá , Publicações , ComunicaçãoRESUMO
Leveraging ~10 years of prospective longitudinal data on 704 participants, we examined the effects of adolescent versus young adult cannabis initiation on MRI-assessed cortical thickness development and behavior. Data were obtained from the IMAGEN study conducted across eight European sites. We identified IMAGEN participants who reported being cannabis-naïve at baseline and had data available at baseline, 5-year, and 9-year follow-up visits. Cannabis use was assessed with the European School Survey Project on Alcohol and Drugs. T1-weighted MR images were processed through the CIVET pipeline. Cannabis initiation occurring during adolescence (14-19 years) and young adulthood (19-22 years) was associated with differing patterns of longitudinal cortical thickness change. Associations between adolescent cannabis initiation and cortical thickness change were observed primarily in dorso- and ventrolateral portions of the prefrontal cortex. In contrast, cannabis initiation occurring between 19 and 22 years of age was associated with thickness change in temporal and cortical midline areas. Follow-up analysis revealed that longitudinal brain change related to adolescent initiation persisted into young adulthood and partially mediated the association between adolescent cannabis use and past-month cocaine, ecstasy, and cannabis use at age 22. Extent of cannabis initiation during young adulthood (from 19 to 22 years) had an indirect effect on psychotic symptoms at age 22 through thickness change in temporal areas. Results suggest that developmental timing of cannabis exposure may have a marked effect on neuroanatomical correlates of cannabis use as well as associated behavioral sequelae. Critically, this work provides a foundation for neurodevelopmentally informed models of cannabis exposure in humans.
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BACKGROUND: Mozart's "Sonata for two pianos" (Köchel listing 448) has proven effective as music therapy for patients with epilepsy, but little is understood about the mechanism of which feature in it impacted therapeutic effect. This study explored whether tempo in that piece is important for its therapeutic effect. METHODS: We measured the effects of tempo in Mozart's sonata on clinical and electroencephalographic parameters of 147 patients with epilepsy who listened to the music at slow, original, or accelerated speed. As a control, patients listened to Haydn's Symphony no. 94 at original speed. RESULTS: Listening to Mozart's piece at original speed significantly reduced the number of interictal epileptic discharges. It decreased beta power in the frontal, parietal, and occipital regions, suggesting increased auditory attention and reduced visual attention. It also decreased functional connectivity among frontal, parietal, temporal, and occipital brain regions, also suggesting increased auditory attention and reduced visual attention. No such effects were observed after patients listened to the slow or fast version of Mozart's piece, or to Haydn's symphony at normal speed. CONCLUSIONS: These results suggest that Mozart's "Sonata for two pianos" may exert therapeutic effects by regulating attention when played at its original tempo, but not slower or faster. These findings may help guide the design and optimization of music therapy against epilepsy.
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Epilepsia , Musicoterapia , Música , Humanos , Estimulação Acústica/métodos , Epilepsia/terapia , Musicoterapia/métodos , Encéfalo , Percepção Auditiva/fisiologiaRESUMO
Prenatal adversity has been linked to later psychopathology. Yet, research on cumulative prenatal adversity, as well as its interaction with offspring genotype, on brain and behavioral development is scarce. With this study, we aimed to address this gap. In Finnish mother-infant dyads, we investigated the association of a cumulative prenatal adversity sum score (PRE-AS) with (a) child emotional and behavioral problems assessed with the Strengths and Difficulties Questionnaire at 4 and 5 years (N = 1568, 45.3% female), (b) infant amygdalar and hippocampal volumes (subsample N = 122), and (c) its moderation by a hippocampal-specific coexpression polygenic risk score based on the serotonin transporter (SLC6A4) gene. We found that higher PRE-AS was linked to greater child emotional and behavioral problems at both time points, with partly stronger associations in boys than in girls. Higher PRE-AS was associated with larger bilateral infant amygdalar volumes in girls compared to boys, while no associations were found for hippocampal volumes. Further, hyperactivity/inattention in 4-year-old girls was related to both genotype and PRE-AS, the latter partially mediated by right amygdalar volumes as preliminary evidence suggests. Our study is the first to demonstrate a dose-dependent sexually dimorphic relationship between cumulative prenatal adversity and infant amygdalar volumes.
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Genes associated with risk for brain disease exhibit characteristic expression patterns that reflect both anatomical and cell type relationships. Brain-wide transcriptomic patterns of disease risk genes provide a molecular-based signature, based on differential co-expression, that is often unique to that disease. Brain diseases can be compared and aggregated based on the similarity of their signatures which often associates diseases from diverse phenotypic classes. Analysis of 40 common human brain diseases identifies 5 major transcriptional patterns, representing tumor-related, neurodegenerative, psychiatric and substance abuse, and 2 mixed groups of diseases affecting basal ganglia and hypothalamus. Further, for diseases with enriched expression in cortex, single-nucleus data in the middle temporal gyrus (MTG) exhibits a cell type expression gradient separating neurodegenerative, psychiatric, and substance abuse diseases, with unique excitatory cell type expression differentiating psychiatric diseases. Through mapping of homologous cell types between mouse and human, most disease risk genes are found to act in common cell types, while having species-specific expression in those types and preserving similar phenotypic classification within species. These results describe structural and cellular transcriptomic relationships of disease risk genes in the adult brain and provide a molecular-based strategy for classifying and comparing diseases, potentially identifying novel disease relationships.
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Encefalopatias , Transcriptoma , Adulto , Animais , Humanos , Camundongos , Gânglios da Base , Encéfalo/metabolismo , Encefalopatias/genética , Encefalopatias/metabolismo , Perfilação da Expressão Gênica/métodos , Transcriptoma/genética , Transcriptoma/fisiologia , Fatores de RiscoRESUMO
We present the Canadian Open Neuroscience Platform (CONP) portal to answer the research community's need for flexible data sharing resources and provide advanced tools for search and processing infrastructure capacity. This portal differs from previous data sharing projects as it integrates datasets originating from a number of already existing platforms or databases through DataLad, a file level data integrity and access layer. The portal is also an entry point for searching and accessing a large number of standardized and containerized software and links to a computing infrastructure. It leverages community standards to help document and facilitate reuse of both datasets and tools, and already shows a growing community adoption giving access to more than 60 neuroscience datasets and over 70 tools. The CONP portal demonstrates the feasibility and offers a model of a distributed data and tool management system across 17 institutions throughout Canada.
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Bases de Dados Factuais , Software , Canadá , Disseminação de InformaçãoRESUMO
This paper introduces methods and a novel toolbox that efficiently integrates high-dimensional Neural Mass Models (NMMs) specified by two essential components. The first is the set of nonlinear Random Differential Equations (RDEs) of the dynamics of each neural mass. The second is the highly sparse three-dimensional Connectome Tensor (CT) that encodes the strength of the connections and the delays of information transfer along the axons of each connection. To date, simplistic assumptions prevail about delays in the CT, often assumed to be Dirac-delta functions. In reality, delays are distributed due to heterogeneous conduction velocities of the axons connecting neural masses. These distributed-delay CTs are challenging to model. Our approach implements these models by leveraging several innovations. Semi-analytical integration of RDEs is done with the Local Linearization (LL) scheme for each neural mass, ensuring dynamical fidelity to the original continuous-time nonlinear dynamic. This semi-analytic LL integration is highly computationally-efficient. In addition, a tensor representation of the CT facilitates parallel computation. It also seamlessly allows modeling distributed delays CT with any level of complexity or realism. This ease of implementation includes models with distributed-delay CTs. Consequently, our algorithm scales linearly with the number of neural masses and the number of equations they are represented with, contrasting with more traditional methods that scale quadratically at best. To illustrate the toolbox's usefulness, we simulate a single Zetterberg-Jansen and Rit (ZJR) cortical column, a single thalmo-cortical unit, and a toy example comprising 1000 interconnected ZJR columns. These simulations demonstrate the consequences of modifying the CT, especially by introducing distributed delays. The examples illustrate the complexity of explaining EEG oscillations, e.g., split alpha peaks, since they only appear for distinct neural masses. We provide an open-source Script for the toolbox.
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Conectoma , Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Simulação por Computador , Axônios , AlgoritmosRESUMO
Few studies have examined the association between conduct problems and cerebral cortical development. Herein, we characterize the association between age-related brain change and conduct problems in a large longitudinal, community-based sample of adolescents. 1,039 participants from the IMAGEN study possessed psychopathology and surface-based morphometric data at study baseline (M = 14.42 years, SD = 0.40; 559 females) and 5-year follow-up. Self-reports of conduct problems were obtained using the Strengths and Difficulties Questionnaire (SDQ). Vertex-level linear mixed effects models were implemented using the Matlab toolbox, SurfStat. To investigate the extent to which cortical thickness maturation was qualified by dimensional measures of conduct problems, we tested for an interaction between age and SDQ Conduct Problems (CP) score. There was no main effect of CP score on cortical thickness; however, a significant "Age by CP" interaction was revealed in bilateral insulae, left inferior frontal gyrus, left rostral anterior cingulate, left posterior cingulate, and bilateral inferior parietal cortices. Across regions, follow-up analysis revealed higher levels of CP were associated with accelerated age-related thinning. Findings were not meaningfully altered when controlling for alcohol use, co-occurring psychopathology, and socioeconomic status. Results may help to further elucidate neurodevelopmental patterns linking adolescent conduct problems with adverse adult outcomes.
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Córtex Cerebral , Imageamento por Ressonância Magnética , Adulto , Feminino , Adolescente , Humanos , Imageamento por Ressonância Magnética/métodos , Córtex Cerebral/patologia , Córtex Pré-Frontal/patologia , Emoções , Lobo ParietalRESUMO
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder diagnosed based on social impairment, restricted interests, and repetitive behaviors. Contemporary theories posit that cerebellar pathology contributes causally to ASD by disrupting error-based learning (EBL) during infancy. The present study represents the first test of this theory in a prospective infant sample, with potential implications for ASD detection. Methods: Data from the Infant Brain Imaging Study (n = 94, 68 male) were used to examine 6-month cerebellar functional connectivity magnetic resonance imaging in relation to later (12/24-month) ASD-associated behaviors and outcomes. Hypothesis-driven univariate analyses and machine learning-based predictive tests examined cerebellar-frontoparietal network (FPN; subserves error signaling in support of EBL) and cerebellar-default mode network (DMN; broadly implicated in ASD) connections. Cerebellar-FPN functional connectivity was used as a proxy for EBL, and cerebellar-DMN functional connectivity provided a comparative foil. Data-driven functional connectivity magnetic resonance imaging enrichment examined brain-wide behavioral associations, with post hoc tests of cerebellar connections. Results: Cerebellar-FPN and cerebellar-DMN connections did not demonstrate associations with ASD. Functional connectivity magnetic resonance imaging enrichment identified 6-month correlates of later ASD-associated behaviors in networks of a priori interest (FPN, DMN), as well as in cingulo-opercular (also implicated in error signaling) and medial visual networks. Post hoc tests did not suggest a role for cerebellar connections. Conclusions: We failed to identify cerebellar functional connectivity-based contributions to ASD. However, we observed prospective correlates of ASD-associated behaviors in networks that support EBL. Future studies may replicate and extend network-level positive results, and tests of the cerebellum may investigate brain-behavior associations at different developmental stages and/or using different neuroimaging modalities.
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Essential tremor (ET) is the most prevalent movement disorder with poorly understood etiology. Some neuroimaging studies report cerebellar involvement whereas others do not. This discrepancy may stem from underpowered studies, differences in statistical modeling or variation in magnetic resonance imaging (MRI) acquisition and processing. To resolve this, we investigated the cerebellar structural differences using a local advanced ET dataset augmented by matched controls from PPMI and ADNI. We tested the hypothesis of cerebellar involvement using three neuroimaging biomarkers: VBM, gray/white matter volumetry and lobular volumetry. Furthermore, we assessed the impacts of statistical models and segmentation pipelines on results. Results indicate that the detected cerebellar structural changes vary with methodology. Significant reduction of right cerebellar gray matter and increase of the left cerebellar white matter were the only two biomarkers consistently identified by multiple methods. Results also show substantial volumetric overestimation from SUIT-based segmentation-partially explaining previous literature discrepancies. This study suggests that current estimation of cerebellar involvement in ET may be overemphasized in MRI studies and highlights the importance of methods sensitivity analysis on results interpretation. ET datasets with large sample size and replication studies are required to improve our understanding of regional specificity of cerebellum involvement in ET. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 21 March 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.6084/m9.figshare.19697776 .
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Tremor Essencial , Humanos , Tremor Essencial/diagnóstico por imagem , Tremor Essencial/patologia , Reprodutibilidade dos Testes , Consenso , Imageamento por Ressonância Magnética/métodos , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologiaRESUMO
Studies have shown cortical alterations in individuals with autism spectrum disorders (ASD) as well as in individuals with high polygenic risk for ASD. An important addition to the study of altered cortical anatomy is the investigation of the underlying brain network architecture that may reveal brain-wide mechanisms in ASD and in polygenic risk for ASD. Such an approach has been proven useful in other psychiatric disorders by revealing that brain network architecture shapes (to an extent) the disorder-related cortical alterations. This study uses data from a clinical dataset-560 male subjects (266 individuals with ASD and 294 healthy individuals, CTL, mean age at 17.2 years) from the Autism Brain Imaging Data Exchange database, and data of 391 healthy individuals (207 males, mean age at 12.1 years) from the Pediatric Imaging, Neurocognition and Genetics database. ASD-related cortical alterations (group difference, ASD-CTL, in cortical thickness) and cortical correlates of polygenic risk for ASD were assessed, and then statistically compared with structural connectome-based network measures (such as hubs) using spin permutation tests. Next, we investigated whether polygenic risk for ASD could be predicted by network architecture by building machine-learning based prediction models, and whether the top predictors of the model were identified as disease epicenters of ASD. We observed that ASD-related cortical alterations as well as cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. We also observed that age progression of ASD-related cortical alterations and cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. Further investigation revealed that structural connectomes predicted polygenic risk for ASD (r = 0.30, p < 0.0001), and two brain regions (the left inferior parietal and left suparmarginal) with top predictive connections were identified as disease epicenters of ASD. Our study highlights a critical role of network architecture in a continuum model of ASD spanning from healthy individuals with genetic risk to individuals with ASD. Our study also highlights the strength of investigating polygenic risk scores in addition to multi-modal neuroimaging measures to better understand the interplay between genetic risk and brain alterations associated with ASD.
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Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Masculino , Criança , Adolescente , Imageamento por Ressonância Magnética/métodos , Encéfalo , NeuroimagemRESUMO
We previously proposed a structure for recording consent-based data use 'categories' and 'requirements' - Consent Codes - with a view to supporting maximum use and integration of genomic research datasets, and reducing uncertainty about permissible re-use of shared data. Here we discuss clarifications and subsequent updates to the Consent Codes (v4) based on new areas of application (e.g., the neurosciences, biobanking, H3Africa), policy developments (e.g., return of research results), and further practical considerations, including developments in automated approaches to consent management.
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Bancos de Espécimes Biológicos , Consentimento Livre e Esclarecido , Ecossistema , GenômicaRESUMO
The absence of disease modifying treatments for amyotrophic lateral sclerosis (ALS) is in large part a consequence of its complexity and heterogeneity. Deep clinical and biological phenotyping of people living with ALS would assist in the development of effective treatments and target specific biomarkers to monitor disease progression and inform on treatment efficacy. The objective of this paper is to present the Comprehensive Analysis Platform To Understand Remedy and Eliminate ALS (CAPTURE ALS), an open and translational platform for the scientific community currently in development. CAPTURE ALS is a Canadian-based platform designed to include participants' voices in its development and through execution. Standardized methods will be used to longitudinally characterize ALS patients and healthy controls through deep clinical phenotyping, neuroimaging, neurocognitive and speech assessments, genotyping and multisource biospecimen collection. This effort plugs into complementary Canadian and international initiatives to share common resources. Here, we describe in detail the infrastructure, operating procedures, and long-term vision of CAPTURE ALS to facilitate and accelerate translational ALS research in Canada and beyond.