RESUMO
Recent advances in imaging and tracing technology provide increasingly detailed reconstructions of brain connectomes. Concomitant analytic advances enable rigorous identification and quantification of functionally important features of brain network architecture. Null models are a flexible tool to statistically benchmark the presence or magnitude of features of interest, by selectively preserving specific architectural properties of brain networks while systematically randomizing others. Here we describe the logic, implementation and interpretation of null models of connectomes. We introduce randomization and generative approaches to constructing null networks, and outline a taxonomy of network methods for statistical inference. We highlight the spectrum of null models - from liberal models that control few network properties, to conservative models that recapitulate multiple properties of empirical networks - that allow us to operationalize and test detailed hypotheses about the structure and function of brain networks. We review emerging scenarios for the application of null models in network neuroscience, including for spatially embedded networks, annotated networks and correlation-derived networks. Finally, we consider the limits of null models, as well as outstanding questions for the field.
Assuntos
Conectoma , Neurociências , Encéfalo , Conectoma/métodos , Humanos , Rede NervosaRESUMO
Adolescent development of human brain structural and functional networks is increasingly recognized as fundamental to emergence of typical and atypical adult cognitive and emotional proodal magnetic resonance imaging (MRI) data collected from N [Formula: see text] 300 healthy adolescents (51%; female; 14 to 26 y) each scanned repeatedly in an accelerated longitudinal design, to provide an analyzable dataset of 469 structural scans and 448 functional MRI scans. We estimated the morphometric similarity between each possible pair of 358 cortical areas on a feature vector comprising six macro- and microstructural MRI metrics, resulting in a morphometric similarity network (MSN) for each scan. Over the course of adolescence, we found that morphometric similarity increased in paralimbic cortical areas, e.g., insula and cingulate cortex, but generally decreased in neocortical areas, and these results were replicated in an independent developmental MRI cohort (N [Formula: see text] 304). Increasing hubness of paralimbic nodes in MSNs was associated with increased strength of coupling between their morphometric similarity and functional connectivity. Decreasing hubness of neocortical nodes in MSNs was associated with reduced strength of structure-function coupling and increasingly diverse functional connections in the corresponding fMRI networks. Neocortical areas became more structurally differentiated and more functionally integrative in a metabolically expensive process linked to cortical thinning and myelination, whereas paralimbic areas specialized for affective and interoceptive functions became less differentiated, as hypothetically predicted by a developmental transition from periallocortical to proisocortical organization of the cortex. Cytoarchitectonically distinct zones of the human cortex undergo distinct neurodevelopmental programs during typical adolescence.
Assuntos
Imageamento por Ressonância Magnética , Neocórtex , Humanos , Adolescente , Feminino , Masculino , Neocórtex/diagnóstico por imagem , Neocórtex/crescimento & desenvolvimento , Neocórtex/fisiologia , Adulto , Adulto Jovem , Mapeamento Encefálico/métodos , Desenvolvimento do Adolescente/fisiologia , Rede Nervosa/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/crescimento & desenvolvimento , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Encéfalo/fisiologiaRESUMO
Childhood adversity is one of the strongest predictors of adolescent mental illness. Therefore, it is critical that the mechanisms that aid resilient functioning in individuals exposed to childhood adversity are better understood. Here, we examined whether resilient functioning was related to structural brain network topology. We quantified resilient functioning at the individual level as psychosocial functioning adjusted for the severity of childhood adversity in a large sample of adolescents (N = 2406, aged 14-24). Next, we examined nodal degree (the number of connections that brain regions have in a network) using brain-wide cortical thickness measures in a representative subset (N = 275) using a sliding window approach. We found that higher resilient functioning was associated with lower nodal degree of multiple regions including the dorsolateral prefrontal cortex, the medial prefrontal cortex, and the posterior superior temporal sulcus (z > 1.645). During adolescence, decreases in nodal degree are thought to reflect a normative developmental process that is part of the extensive remodeling of structural brain network topology. Prior findings in this sample showed that decreased nodal degree was associated with age, as such our findings of negative associations between nodal degree and resilient functioning may therefore potentially resemble a more mature structural network configuration in individuals with higher resilient functioning.
Assuntos
Experiências Adversas da Infância , Transtornos Mentais , Resiliência Psicológica , Humanos , Adolescente , Encéfalo/diagnóstico por imagem , Lobo Temporal , Imageamento por Ressonância MagnéticaRESUMO
A characteristic of adaptive behavior is its goal-directed nature. An ability to act in a goal-directed manner is progressively refined during development, but this refinement can be impacted by the emergence of psychiatric disorders. Disorders of compulsivity have been framed computationally as a deficit in model-based control, and have been linked also to abnormal frontostriatal connectivity. However, the developmental trajectory of model-based control, including an interplay between its maturation and an emergence of compulsivity, has not been characterized. Availing of a large sample of healthy adolescents (n = 569) aged 14 to 24 y, we show behaviorally that over the course of adolescence there is a within-person increase in model-based control, and this is more pronounced in younger participants. Using a bivariate latent change score model, we provide evidence that the presence of higher compulsivity traits is associated with an atypical profile of this developmental maturation in model-based control. Resting-state fMRI data from a subset of the behaviorally assessed subjects (n = 230) revealed that compulsivity is associated with a less pronounced change of within-subject developmental remodeling of functional connectivity, specifically between the striatum and a frontoparietal network. Thus, in an otherwise clinically healthy population sample, in early development, individual differences in compulsivity are linked to the developmental trajectory of model-based control and a remodeling of frontostriatal connectivity.
Assuntos
Desenvolvimento do Adolescente , Comportamento Compulsivo/psicologia , Adolescente , Adulto , Comportamento Compulsivo/diagnóstico por imagem , Comportamento Compulsivo/fisiopatologia , Corpo Estriado/diagnóstico por imagem , Feminino , Objetivos , Humanos , Imageamento por Ressonância Magnética , Masculino , Adulto JovemRESUMO
Adolescent changes in human brain function are not entirely understood. Here, we used multiecho functional MRI (fMRI) to measure developmental change in functional connectivity (FC) of resting-state oscillations between pairs of 330 cortical regions and 16 subcortical regions in 298 healthy adolescents scanned 520 times. Participants were aged 14 to 26 y and were scanned on 1 to 3 occasions at least 6 mo apart. We found 2 distinct modes of age-related change in FC: "conservative" and "disruptive." Conservative development was characteristic of primary cortex, which was strongly connected at 14 y and became even more connected in the period from 14 to 26 y. Disruptive development was characteristic of association cortex and subcortical regions, where connectivity was remodeled: connections that were weak at 14 y became stronger during adolescence, and connections that were strong at 14 y became weaker. These modes of development were quantified using the maturational index (MI), estimated as Spearman's correlation between edgewise baseline FC (at 14 y, [Formula: see text]) and adolescent change in FC ([Formula: see text]), at each region. Disruptive systems (with negative MI) were activated by social cognition and autobiographical memory tasks in prior fMRI data and significantly colocated with prior maps of aerobic glycolysis (AG), AG-related gene expression, postnatal cortical surface expansion, and adolescent shrinkage of cortical thickness. The presence of these 2 modes of development was robust to numerous sensitivity analyses. We conclude that human brain organization is disrupted during adolescence by remodeling of FC between association cortical and subcortical areas.
Assuntos
Desenvolvimento do Adolescente/fisiologia , Encéfalo/crescimento & desenvolvimento , Rede Nervosa/crescimento & desenvolvimento , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Conectoma , Feminino , Movimentos da Cabeça/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Adulto JovemRESUMO
Current neuroimaging acquisition and processing approaches tend to be optimised for quality rather than speed. However, rapid acquisition and processing of neuroimaging data can lead to novel neuroimaging paradigms, such as adaptive acquisition, where rapidly processed data is used to inform subsequent image acquisition steps. Here we first evaluate the impact of several processing steps on the processing time and quality of registration of manually labelled T1 -weighted MRI scans. Subsequently, we apply the selected rapid processing pipeline both to rapidly acquired multicontrast EPImix scans of 95 participants (which include T1 -FLAIR, T2 , T2 *, T2 -FLAIR, DWI and ADC contrasts, acquired in ~1 min), as well as to slower, more standard single-contrast T1 -weighted scans of a subset of 66 participants. We quantify the correspondence between EPImix T1 -FLAIR and single-contrast T1 -weighted scans, using correlations between voxels and regions of interest across participants, measures of within- and between-participant identifiability as well as regional structural covariance networks. Furthermore, we explore the use of EPImix for the rapid construction of morphometric similarity networks. Finally, we quantify the reliability of EPImix-derived data using test-retest scans of 10 participants. Our results demonstrate that quantitative information can be derived from a neuroimaging scan acquired and processed within minutes, which could further be used to implement adaptive multimodal imaging and tailor neuroimaging examinations to individual patients.
Assuntos
Encéfalo , Neuroimagem , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal , Neuroimagem/métodos , Reprodutibilidade dos TestesRESUMO
Seminal human brain histology work has demonstrated developmental waves of myelination. Here, using a micro-structural magnetic resonance imaging (MRI) marker linked to myelin, we studied fine-grained age differences to deduce waves of growth, stability, and decline of cortical myelination over the life-cycle. In 484 participants, aged 8-85 years, we fitted smooth growth curves to T1- to T2-weighted ratio in each of 360 regions from one of seven cytoarchitectonic classes. From the first derivatives of these generally inverted-U trajectories, we defined three milestones: the age at peak growth; the age at onset of a stable plateau; and the age at the onset of decline. Age at peak growth had a bimodal distribution comprising an early (pre-pubertal) wave of primary sensory and motor cortices and a later (post-pubertal) wave of association, insular and limbic cortices. Most regions reached stability in the 30-s but there was a second wave reaching stability in the 50-s. Age at onset of decline was also bimodal: in some right hemisphere regions, the curve declined from the 60-s, but in other left hemisphere regions, there was no significant decline from the stable plateau. These results are consistent with regionally heterogeneous waves of intracortical myelinogenesis and age-related demyelination.
Assuntos
Córtex Cerebral/crescimento & desenvolvimento , Bainha de Mielina/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Conectoma , Feminino , Humanos , Longevidade , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Motivated by prior data on local cortical shrinkage and intracortical myelination, we predicted age-related changes in topological organization of cortical structural networks during adolescence. We estimated structural correlation from magnetic resonance imaging measures of cortical thickness at 308 regions in a sample of N = 297 healthy participants, aged 14-24 years. We used a novel sliding-window analysis to measure age-related changes in network attributes globally, locally and in the context of several community partitions of the network. We found that the strength of structural correlation generally decreased as a function of age. Association cortical regions demonstrated a sharp decrease in nodal degree (hubness) from 14 years, reaching a minimum at approximately 19 years, and then levelling off or even slightly increasing until 24 years. Greater and more prolonged age-related changes in degree of cortical regions within the brain network were associated with faster rates of adolescent cortical myelination and shrinkage. The brain regions that demonstrated the greatest age-related changes were concentrated within prefrontal modules. We conclude that human adolescence is associated with biologically plausible changes in structural imaging markers of brain network organization, consistent with the concept of tuning or consolidating anatomical connectivity between frontal cortex and the rest of the connectome.
Assuntos
Lobo Frontal/diagnóstico por imagem , Adolescente , Estudos de Coortes , Conectoma , Feminino , Lobo Frontal/crescimento & desenvolvimento , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/crescimento & desenvolvimento , Adulto JovemRESUMO
How does human brain structure mature during adolescence? We used MRI to measure cortical thickness and intracortical myelination in 297 population volunteers aged 14-24 y old. We found and replicated that association cortical areas were thicker and less myelinated than primary cortical areas at 14 y. However, association cortex had faster rates of shrinkage and myelination over the course of adolescence. Age-related increases in cortical myelination were maximized approximately at the internal layer of projection neurons. Adolescent cortical myelination and shrinkage were coupled and specifically associated with a dorsoventrally patterned gene expression profile enriched for synaptic, oligodendroglial- and schizophrenia-related genes. Topologically efficient and biologically expensive hubs of the brain anatomical network had greater rates of shrinkage/myelination and were associated with overexpression of the same transcriptional profile as cortical consolidation. We conclude that normative human brain maturation involves a genetically patterned process of consolidating anatomical network hubs. We argue that developmental variation of this consolidation process may be relevant both to normal cognitive and behavioral changes and the high incidence of schizophrenia during human brain adolescence.
Assuntos
Córtex Cerebral/anatomia & histologia , Conectoma/métodos , Adolescente , Adulto , Córtex Cerebral/fisiologia , Cognição , Feminino , Humanos , Masculino , Bainha de Mielina/fisiologia , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Esquizofrenia/fisiopatologia , Transcriptoma , Adulto JovemRESUMO
Functional connectomes are commonly analysed as sparse graphs, constructed by thresholding cross-correlations between regional neurophysiological signals. Thresholding generally retains the strongest edges (correlations), either by retaining edges surpassing a given absolute weight, or by constraining the edge density. The latter (more widely used) method risks inclusion of false positive edges at high edge densities and exclusion of true positive edges at low edge densities. Here we apply new wavelet-based methods, which enable construction of probabilistically-thresholded graphs controlled for type I error, to a dataset of resting-state fMRI scans of 56 patients with schizophrenia and 71 healthy controls. By thresholding connectomes to fixed edge-specific P value, we found that functional connectomes of patients with schizophrenia were more dysconnected than those of healthy controls, exhibiting a lower edge density and a higher number of (dis)connected components. Furthermore, many participants' connectomes could not be built up to the fixed edge densities commonly studied in the literature (â¼5-30%), while controlling for type I error. Additionally, we showed that the topological randomisation previously reported in the schizophrenia literature is likely attributable to "non-significant" edges added when thresholding connectomes to fixed density based on correlation. Finally, by explicitly comparing connectomes thresholded by increasing P value and decreasing correlation, we showed that probabilistically thresholded connectomes show decreased randomness and increased consistency across participants. Our results have implications for future analysis of functional connectivity using graph theory, especially within datasets exhibiting heterogenous distributions of edge weights (correlations), between groups or across participants.
Assuntos
Encéfalo/diagnóstico por imagem , Conectoma/métodos , Interpretação de Imagem Assistida por Computador/métodos , Esquizofrenia/diagnóstico por imagem , Encéfalo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Modelos Teóricos , Esquizofrenia/fisiopatologiaRESUMO
Complex network topology is characteristic of many biological systems, including anatomical and functional brain networks (connectomes). Here, we first constructed a structural covariance network from MRI measures of cortical thickness on 296 healthy volunteers, aged 14-24 years. Next, we designed a new algorithm for matching sample locations from the Allen Brain Atlas to the nodes of the SCN. Subsequently we used this to define, transcriptomic brain networks by estimating gene co-expression between pairs of cortical regions. Finally, we explored the hypothesis that transcriptional networks and structural MRI connectomes are coupled. A transcriptional brain network (TBN) and a structural covariance network (SCN) were correlated across connection weights and showed qualitatively similar complex topological properties: assortativity, small-worldness, modularity, and a rich-club. In both networks, the weight of an edge was inversely related to the anatomical (Euclidean) distance between regions. There were differences between networks in degree and distance distributions: the transcriptional network had a less fat-tailed degree distribution and a less positively skewed distance distribution than the SCN. However, cortical areas connected to each other within modules of the SCN had significantly higher levels of whole genome co-expression than expected by chance. Nodes connected in the SCN had especially high levels of expression and co-expression of a human supragranular enriched (HSE) gene set that has been specifically located to supragranular layers of human cerebral cortex and is known to be important for large-scale, long-distance cortico-cortical connectivity. This coupling of brain transcriptome and connectome topologies was largely but not entirely accounted for by the common constraint of physical distance on both networks.
Assuntos
Algoritmos , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Conectoma/métodos , Adolescente , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa , Transcriptoma/fisiologia , Adulto JovemRESUMO
At the macroscopic scale, the human brain can be described as a complex network of white matter tracts integrating grey matter assemblies - the human connectome. The structure of the connectome, which is often described using graph theoretic approaches, can be used to model macroscopic brain function at low computational cost. Here, we use the Kuramoto model of coupled oscillators with time-delays, calibrated with respect to empirical functional MRI data, to study the relation between the structure of the connectome and two aspects of functional brain dynamics - synchrony, a measure of general coherence, and metastability, a measure of dynamical flexibility. Specifically, we investigate the relationship between the local structure of the connectome, quantified using graph theory, and the synchrony and metastability of the model's dynamics. By removing individual nodes and all of their connections from the model, we study the effect of lesions on both global and local dynamics. Of the nine nodal graph-theoretical properties tested, two were able to predict effects of node lesion on the global dynamics. The removal of nodes with high eigenvector centrality leads to decreases in global synchrony and increases in global metastability, as does the removal of hub nodes joining topologically segregated network modules. At the level of local dynamics in the neighbourhood of the lesioned node, structural properties of the lesioned nodes hold more predictive power, as five nodal graph theoretical measures are related to changes in local dynamics following node lesions. We discuss these results in the context of empirical studies of stroke and functional brain dynamics.
Assuntos
Córtex Cerebral/lesões , Córtex Cerebral/fisiopatologia , Conectoma , Modelos Neurológicos , Rede Nervosa/fisiologia , Simulação por Computador , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Recent theories of cortical organisation suggest features of function emerge from the spatial arrangement of brain regions. For example, association cortex is located furthest from systems involved in action and perception. Association cortex is also 'interdigitated' with adjacent regions having different patterns of functional connectivity. It is assumed that topographic properties, such as distance between regions, constrains their functions, however, we lack a formal description of how this occurs. Here we use variograms, a quantification of spatial autocorrelation, to profile how function changes with the distance between cortical regions. We find function changes with distance more gradually within sensory-motor cortex than association cortex. Importantly, systems within the same type of cortex (e.g., fronto-parietal and default mode networks) have similar profiles. Primary and association cortex, therefore, are differentiated by how function changes over space, emphasising the value of topographical features of a region when estimating its contribution to cognition and behaviour.
Assuntos
Cognição , Córtex Sensório-Motor , Análise EspacialRESUMO
The multicontrast EPImix sequence generates six contrasts, including a T1-weighted scan, in ~1 min. EPImix shows comparable diagnostic performance to conventional scans under qualitative clinical evaluation, and similarities in simple quantitative measures including contrast intensity. However, EPImix scans have not yet been compared to standard MRI scans using established quantitative measures. In this study, we compared conventional and EPImix-derived T1-weighted scans of 64 healthy participants using tissue volume estimates and predicted brain-age. All scans were pre-processed using the SPM12 DARTEL pipeline, generating measures of grey matter, white matter and cerebrospinal fluid volume. Brain-age was predicted using brainageR, a Gaussian Processes Regression model previously trained on a large sample of standard T1-weighted scans. Estimates of both global and voxel-wise tissue volume showed significantly similar results between standard and EPImix-derived T1-weighted scans. Brain-age estimates from both sequences were significantly correlated, although EPImix T1-weighted scans showed a systematic offset in predictions of chronological age. Supplementary analyses suggest that this is likely caused by the reduced field of view of EPImix scans, and the use of a brain-age model trained using conventional T1-weighted scans. However, this systematic error can be corrected using additional regression of T1-predicted brain-age onto EPImix-predicted brain-age. Finally, retest EPImix scans acquired for 10 participants demonstrated high test-retest reliability in all evaluated quantitative measurements. Quantitative analysis of EPImix scans has potential to reduce scanning time, increasing participant comfort and reducing cost, as well as to support automation of scanning, utilising active learning for faster and individually-tailored (neuro)imaging.
Assuntos
Imageamento por Ressonância Magnética , Neuroimagem , Encéfalo/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Reprodutibilidade dos TestesRESUMO
The study of complex systems deals with emergent behavior that arises as a result of nonlinear spatiotemporal interactions between a large number of components both within the system, as well as between the system and its environment. There is a strong case to be made that neural systems as well as their emergent behavior and disorders can be studied within the framework of complexity science. In particular, the field of neuroimaging has begun to apply both theoretical and experimental procedures originating in complexity science-usually in parallel with traditional methodologies. Here, we illustrate the basic properties that characterize complex systems and evaluate how they relate to what we have learned about brain structure and function from neuroimaging experiments. We then argue in favor of adopting a complex systems-based methodology in the study of neuroimaging, alongside appropriate experimental paradigms, and with minimal influences from noncomplex system approaches. Our exposition includes a review of the fundamental mathematical concepts, combined with practical examples and a compilation of results from the literature.
Assuntos
Encéfalo , Neuroimagem , Encéfalo/diagnóstico por imagem , Humanos , Neuroimagem/métodosRESUMO
For most neuroimaging questions the range of possible analytic choices makes it unclear how to evaluate conclusions from any single analytic method. One possible way to address this issue is to evaluate all possible analyses using a multiverse approach, however, this can be computationally challenging and sequential analyses on the same data can compromise predictive power. Here, we establish how active learning on a low-dimensional space capturing the inter-relationships between pipelines can efficiently approximate the full spectrum of analyses. This approach balances the benefits of a multiverse analysis without incurring the cost on computational and predictive power. We illustrate this approach with two functional MRI datasets (predicting brain age and autism diagnosis) demonstrating how a multiverse of analyses can be efficiently navigated and mapped out using active learning. Furthermore, our presented approach not only identifies the subset of analysis techniques that are best able to predict age or classify individuals with autism spectrum disorder and healthy controls, but it also allows the relationships between analyses to be quantified.
Assuntos
Transtorno do Espectro Autista , Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodosRESUMO
Sexual differences in human brain development could be relevant to sex differences in the incidence of depression during adolescence. We tested for sex differences in parameters of normative brain network development using fMRI data on N = 298 healthy adolescents, aged 14 to 26 years, each scanned one to three times. Sexually divergent development of functional connectivity was located in the default mode network, limbic cortex, and subcortical nuclei. Females had a more "disruptive" pattern of development, where weak functional connectivity at age 14 became stronger during adolescence. This fMRI-derived map of sexually divergent brain network development was robustly colocated with i prior loci of reward-related brain activation ii a map of functional dysconnectivity in major depressive disorder (MDD), and iii an adult brain gene transcriptional pattern enriched for genes on the X chromosome, neurodevelopmental genes, and risk genes for MDD. We found normative sexual divergence in adolescent development of a cortico-subcortical brain functional network that is relevant to depression.
Assuntos
Transtorno Depressivo Maior , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Depressão/genética , Transtorno Depressivo Maior/genética , Feminino , Humanos , Masculino , Vias NeuraisRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
Neurodevelopmental disorders have a heritable component and are associated with region specific alterations in brain anatomy. However, it is unclear how genetic risks for neurodevelopmental disorders are translated into spatially patterned brain vulnerabilities. Here, we integrated cortical neuroimaging data from patients with neurodevelopmental disorders caused by genomic copy number variations (CNVs) and gene expression data from healthy subjects. For each of the six investigated disorders, we show that spatial patterns of cortical anatomy changes in youth are correlated with cortical spatial expression of CNV genes in neurotypical adults. By transforming normative bulk-tissue cortical expression data into cell-type expression maps, we link anatomical change maps in each analysed disorder to specific cell classes as well as the CNV-region genes they express. Our findings reveal organizing principles that regulate the mapping of genetic risks onto regional brain changes in neurogenetic disorders. Our findings will enable screening for candidate molecular mechanisms from readily available neuroimaging data.
Assuntos
Córtex Cerebral/patologia , Variações do Número de Cópias de DNA , Predisposição Genética para Doença , Transtornos do Neurodesenvolvimento/genética , Adolescente , Adulto , Mapeamento Encefálico , Córtex Cerebral/citologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/crescimento & desenvolvimento , Criança , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Genoma Humano , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/patologia , Neuroimagem , Neurônios/metabolismo , Neurônios/patologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Análise Espacial , Adulto JovemRESUMO
Understanding how variations in dimensions of psychometrics, IQ and demographics relate to changes in brain connectivity during the critical developmental period of adolescence and early adulthood is a major challenge. This has particular relevance for mental health disorders where a failure to understand these links might hinder the development of better diagnostic approaches and therapeutics. Here, we investigated this question in 306 adolescents and young adults (14-24 y, 25 clinically depressed) using a multivariate statistical framework, based on canonical correlation analysis (CCA). By linking individual functional brain connectivity profiles to self-report questionnaires, IQ and demographic data we identified two distinct modes of covariation. The first mode mapped onto an externalization/internalization axis and showed a strong association with sex. The second mode mapped onto a well-being/distress axis independent of sex. Interestingly, both modes showed an association with age. Crucially, the changes in functional brain connectivity associated with changes in these phenotypes showed marked developmental effects. The findings point to a role for the default mode, frontoparietal and limbic networks in psychopathology and depression.