Genetic influences on resting-state functional networks: A twin study.
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ABSTRACT:
SUBMITTER: Fu Y
PROVIDER: S-EPMC4704468 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The amplitude of activation in brain resting state networks (RSNs), measured with resting-state functional magnetic resonance imaging, is heritable and genetically correlated across RSNs, indicating pleiotropy. Recent univariate genome-wide association studies (GWASs) explored the genetic underpinnings of individual variation in RSN activity. Yet univariate genomic analyses do not describe the pleiotropic nature of RSNs. In this study, we used a novel multivariate method called genomic structural equation modeling to model latent factors that capture the shared genomic influence on RSNs and to identify single nucleotide polymorphisms (SNPs) and genes driving this pleiotropy. Using summary statistics from GWAS of 21 RSNs reported in UK Biobank (N = 31,688), the genomic latent factor analysis was first conducted in a discovery sample (N = 21,081), and then tested in an independent sample from the same cohort (N = 10,607). In the discovery sample, we show that the genetic organization of RSNs can be best explained by two distinct but correlated genetic factors that divide multimodal association networks and sensory networks. Eleven of the 17 factor loadings were replicated in the independent sample. With the multivariate GWAS, we found and replicated nine independent SNPs associated with the joint architecture of RSNs. Further, by combining the discovery and replication samples, we discovered additional SNP and gene associations with the two factors of RSN amplitude. We conclude that modeling the genetic effects on brain function in a multivariate way is a powerful approach to learn more about the biological mechanisms involved in brain function.
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Project description:Functional magnetic resonance imaging studies have documented the resting human brain to be functionally organized in multiple large-scale networks, called resting-state networks (RSNs). Other brain imaging techniques, such as electroencephalography (EEG) and magnetoencephalography (MEG), have been used for investigating the electrophysiological basis of RSNs. To date, it is largely unclear how neural oscillations measured with EEG and MEG are related to functional connectivity in the resting state. In addition, it remains to be elucidated whether and how the observed neural oscillations are related to the spatial distribution of the network nodes over the cortex. To address these questions, we examined frequency-dependent functional connectivity between the main nodes of several RSNs, spanning large part of the cortex. We estimated connectivity using band-limited power correlations from high-density EEG data collected in healthy participants. We observed that functional interactions within RSNs are characterized by a specific combination of neuronal oscillations in the alpha (8-13 Hz), beta (13-30 Hz), and gamma (30-80 Hz) bands, which highly depend on the position of the network nodes. This finding may contribute to a better understanding of the mechanisms through which neural oscillations support functional connectivity in the brain.
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Project description:Functional connectivity within resting-state networks (RSN-FC) is vital for cognitive functioning. RSN-FC is heritable and partially translates to the anatomic architecture of white matter, but the genetic component of structural connections of RSNs (RSN-SC) and their potential genetic overlap with RSN-FC remain unknown. Here, we perform genome-wide association studies (N discovery = 24,336; N replication = 3412) and annotation on RSN-SC and RSN-FC. We identify genes for visual network-SC that are involved in axon guidance and synaptic functioning. Genetic variation in RSN-FC impacts biological processes relevant to brain disorders that previously were only phenotypically associated with RSN-FC alterations. Correlations of the genetic components of RSNs are mostly observed within the functional domain, whereas less overlap is observed within the structural domain and between the functional and structural domains. This study advances the understanding of the complex functional organization of the brain and its structural underpinnings from a genetics viewpoint.
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Project description:BackgroundRed wine and dairy products have been staples in human diets for a long period. However, the impact of red wine and dairy intake on brain network activity remains ambiguous and requires further investigation.MethodsThis study investigated the associations between dairy and red wine consumption and seven neural networks' connectivity with functional magnetic resonance imaging (fMRI) data from a sub-cohort of the UK Biobank database. Linear mixed models were employed to regress dairy and red wine consumption against the intrinsic functional connectivity for each neural network. Interactions with Alzheimer's disease (AD) risk factors, including apolipoprotein E4 (APOE4) genotype, TOMM40 genotype, and family history of AD, were also assessed.ResultMore red wine consumption was associated with enhanced connectivity in the central executive function network and posterior default mode network. Greater milk intake was correlated with more left executive function network connectivity, while higher cheese consumption was linked to reduced posterior default mode network connectivity. For participants without a family history of Alzheimer's disease (AD), increased red wine consumption was positively correlated with enhanced left executive function network connectivity. In contrast, participants with a family history of AD displayed diminished network connectivity in relation to their red wine consumption. The association between cheese consumption and neural network connectivity was influenced by APOE4 status, TOMM40 status, and family history, exhibiting contrasting patterns across different subgroups.ConclusionThe findings of this study indicate that family history modifies the relationship between red wine consumption and network strength. The interaction effects between cheese intake and network connectivity may vary depending on the presence of different genetic factors.
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Project description:Neurobiological theories posit that schizophrenia relates to disturbances in connectivity between brain regions. Resting-state functional magnetic resonance imaging is a powerful tool for examining functional connectivity and has revealed several canonical brain networks, including the default mode, dorsal attention, executive control, and salience networks. The purpose of this study was to examine changes in these networks in schizophrenia. 42 patients with schizophrenia and 61 healthy subjects completed a RS-fMRI scanning session. Seed-based region-of-interest correlation analysis was used to identify the default mode, dorsal attention, executive control, and salience networks. Compared to healthy subjects, individuals with schizophrenia demonstrated greater connectivity between the posterior cingulate cortex, a key hub of the default mode, and the left inferior gyrus, left middle frontal gyrus, and left middle temporal gyrus. Interestingly, these regions were more strongly connected to the executive control network in healthy control subjects. In contrast to the default mode, patients demonstrated less connectivity in the executive control and dorsal attention networks. No differences were observed in the salience network. The results indicate that resting-state networks are differentially affected in schizophrenia. The alterations are characterized by reduced segregation between the default mode and executive control networks in the prefrontal cortex and temporal lobe, and reduced connectivity in the dorsal attention and executive control networks. The changes suggest that the process of functional specialization is altered in schizophrenia. Further work is needed to determine if the alterations are related to disturbances in white matter connectivity, neurodevelopmental abnormalities, and genetic risk for schizophrenia.
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Project description:Delineation of large-scale functional networks (FNs) from resting state functional MRI data has become a standard tool to explore the functional brain organization in neuroscience. However, existing methods sacrifice subject specific variation in order to maintain the across-subject correspondence necessary for group-level analyses. In order to obtain subject specific FNs that are comparable across subjects, existing brain decomposition techniques typically adopt heuristic strategies or assume a specific statistical distribution for the FNs across subjects, and therefore might yield biased results. Here we present a novel data-driven method for detecting subject specific FNs while establishing group level correspondence. Our method simultaneously computes subject specific FNs for a group of subjects regularized by group sparsity, to generate subject specific FNs that are spatially sparse and share common spatial patterns across subjects. Our method is built upon non-negative matrix decomposition techniques, enhanced by a data locality regularization term that makes the decomposition robust to imaging noise and improves spatial smoothness and functional coherences of the subject specific FNs. Our method also adopts automatic relevance determination techniques to eliminate redundant FNs in order to generate a compact set of informative sparse FNs. We have validated our method based on simulated, task fMRI, and resting state fMRI datasets. The experimental results have demonstrated our method could obtain subject specific, sparse, non-negative FNs with improved functional coherence, providing enhanced ability for characterizing the functional brain of individual subjects.
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Project description:Studies of large-scale brain functional connectivity using the resting-state functional magnetic resonance imaging have advanced our understanding of human brain functions. Although the evidence of dynamic functional connectivity is accumulating, the variations of functional connectivity over time have not been well characterized. In the present study, we aimed to associate the variations of functional connectivity with the intrinsic activities of resting-state networks during a single resting-state scan by comparing functional connectivity differences between when a network had higher and lower intrinsic activities. The activities of the salience network, default mode network (DMN), and motor network were associated with changes of resting-state functional connectivity. Higher activity of the salience network was accompanied by greater functional connectivity between the fronto-parietal regions and the DMN regions, and between the regions within the DMN. Higher DMN activity was associated with less connectivity between the regions within the DMN, and greater connectivity between the regions within the fronto-parietal network. Higher motor network activity was correlated with greater connectivity between the regions within the motor network, and smaller connectivity between the DMN regions and fronto-parietal regions, and between the DMN regions and the motor regions. In addition, the whole brain network modularity was positively correlated with the motor network activity, suggesting that the brain is more segregated as sub-systems when the motor network is intrinsically activated. Together, these results demonstrate the association between the resting-state connectivity variations and the intrinsic activities of specific networks, which can provide insights on the dynamic changes in large-scale brain connectivity and network configurations.
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