Heritability of Functional Connectivity in Resting State: Assessment of the Dynamic Mean, Dynamic Variance, and Static Connectivity across Networks.
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SUBMITTER: Barber AD
PROVIDER: S-EPMC8325018 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Estimation of functional connectivity (FC) has become an increasingly powerful tool for investigating healthy and abnormal brain function. Static connectivity, in particular, has played a large part in guiding conclusions from the majority of resting-state functional MRI studies. However, accumulating evidence points to the presence of temporal fluctuations in FC, leading to increasing interest in estimating FC as a dynamic quantity. One central issue that has arisen in this new view of connectivity is the dramatic increase in complexity caused by dynamic functional connectivity (dFC) estimation. To computationally handle this increased complexity, a limited set of dFC properties, primarily the mean and variance, have generally been considered. Additionally, it remains unclear how to integrate the increased information from dFC into pattern recognition techniques for subject-level prediction. In this study, we propose an approach to address these two issues based on a large number of previously unexplored temporal and spectral features of dynamic functional connectivity. A Generalized Autoregressive Conditional Heteroskedasticity (GARCH) model is used to estimate time-varying patterns of functional connectivity between resting-state networks. Time-frequency analysis is then performed on dFC estimates, and a large number of previously unexplored temporal and spectral features drawn from signal processing literature are extracted for dFC estimates. We apply the investigated features to two neurologic populations of interest, healthy controls and patients with temporal lobe epilepsy, and show that the proposed approach leads to substantial increases in predictive performance compared to both traditional estimates of static connectivity as well as current approaches to dFC. Variable importance is assessed and shows that there are several quantities that can be extracted from dFC signal which are more informative than the traditional mean or variance of dFC. This work illuminates many previously unexplored facets of the dynamic properties of functional connectivity between resting-state networks, and provides a platform for dynamic functional connectivity analysis that facilitates its usage as an investigative measure for healthy as well as abnormal brain function.
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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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Project description:Spontaneous brain activity is organized into resting-state networks (RSNs) involved in internally-guided, higher-order mental functions (default mode, central executive and salience networks) and externally-driven, specialized sensory and motor processing (auditory, visual and sensorimotor networks). RSNs are characterized by their functional connectivity in terms of within-network cohesion and between-network integration, and by their dynamic properties in terms of synchrony and metastability. We examined the relationship between functional connectivity and dynamic network features using fMRI data and an anatomically constrained Kuramoto model. Extrapolating from simulated data, synchrony and metastability across the RSNs emerged at coupling strengths of 5???k???12. In the empirical RSNs, higher metastability and synchrony were respectively associated with greater cohesion and lower integration. Consistent with their dual role in supporting both sustained and diverse mental operations, higher-order RSNs had lower metastability and synchrony. Sensory and motor RSNs showed greater cohesion and metastability, likely to respectively reflect their functional specialization and their greater capacity for altering network states in response to multiple and diverse external demands. Our findings suggest that functional and dynamic RSN properties are closely linked and expand our understanding of the neural architectures that support optimal brain function.
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Project description:Prior research has shown that during development, there is increased segregation between, and increased integration within, prototypical resting-state functional brain networks. Functional networks are typically defined by static functional connectivity over extended periods of rest. However, little is known about how time-varying properties of functional networks change with age. Likewise, a comparison of standard approaches to functional connectivity may provide a nuanced view of how network integration and segregation are reflected across the lifespan. Therefore, this exploratory study evaluated common approaches to static and dynamic functional network connectivity in a publicly available dataset of subjects ranging from 8 to 75 years of age. Analyses evaluated relationships between age and static resting-state functional connectivity, variability (standard deviation) of connectivity, and mean dwell time of functional network states defined by recurring patterns of whole-brain connectivity. Results showed that older age was associated with decreased static connectivity between nodes of different canonical networks, particularly between the visual system and nodes in other networks. Age was not significantly related to variability of connectivity. Mean dwell time of a network state reflecting high connectivity between visual regions decreased with age, but older age was also associated with increased mean dwell time of a network state reflecting high connectivity within and between canonical sensorimotor and visual networks. Results support a model of increased network segregation over the lifespan and also highlight potential pathways of top-down regulation among networks.
| S-EPMC7752769 | biostudies-literature
Project description:In order to explore the topological alterations in functional brain networks between multiple system atrophy (MSA) patients and healthy controls (HC), a new joint analysis method of static and dynamic functional connectivity (FC) is proposed in this paper. Twenty-four MSA patients and twenty HCs were enrolled in this study. We constructed static and dynamic brain networks from resting-state fMRI data and calculated four graph theory attributes. Statistical comparisons and correlation analysis were carried out for static and dynamic FC separately before combining both cases. We found decreased local efficiency (LE) and weighted degree (WD) in cerebellum from both static and dynamic graph attributes. For static FC alone, we identified increased betweenness centrality (BC) at left dorsolateral prefrontal cortex, left Cerebellum_Crus9 and decreased WD at Vermis_6. For dynamic FC alone, decreased BC, clustering coefficients and LE at several cortical regions and cerebellum were identified. All the features had significant correlation with total UMSARS scores. Receiver operating characteristic analysis showed that dynamic features had the highest area under the curve value. Our work not only added new evidence for the underlying neurobiology and disrupted dynamic disconnection syndrome of MSA, but also proved the possibility of disease diagnosis and progression tracking using rs-fMRI.
| S-EPMC7485713 | biostudies-literature
Project description:Recently, functional network connectivity (FNC, defined as the temporal correlation among spatially distant brain networks) has been used to examine the functional organization of brain networks in various psychiatric illnesses. Dynamic FNC is a recent extension of the conventional FNC analysis that takes into account FNC changes over short periods of time. While such dynamic FNC measures may be more informative about various aspects of connectivity, there has been no detailed head-to-head comparison of the ability of static and dynamic FNC to perform classification in complex mental illnesses. This paper proposes a framework for automatic classification of schizophrenia, bipolar and healthy subjects based on their static and dynamic FNC features. Also, we compare cross-validated classification performance between static and dynamic FNC. Results show that the dynamic FNC significantly outperforms the static FNC in terms of predictive accuracy, indicating that features from dynamic FNC have distinct advantages over static FNC for classification purposes. Moreover, combining static and dynamic FNC features does not significantly improve the classification performance over the dynamic FNC features alone, suggesting that static FNC does not add any significant information when combined with dynamic FNC for classification purposes. A three-way classification methodology based on static and dynamic FNC features discriminates individual subjects into appropriate diagnostic groups with high accuracy. Our proposed classification framework is potentially applicable to additional mental disorders.
| S-EPMC4912868 | biostudies-literature
Project description:The resting activity of the brain can be described by so-called intrinsic connectivity networks (ICNs), which consist of spatially and temporally distributed, but functionally connected, nodes. The coordinated activity of the resting state can be explored via magnetoencephalography (MEG) by studying frequency-dependent functional brain networks at the source level. Although many algorithms for the analysis of brain connectivity have been proposed, the reliability of network metrics derived from both static and dynamic functional connectivity is still unknown. This is a particular problem for studies of associations between ICN metrics and personality variables or other traits, and for studies of differences between patient and control groups, which both depend critically on the reliability of the metrics used. A detailed investigation of the reliability of metrics derived from resting-state MEG repeat scans is therefore a prerequisite for the development of connectomic biomarkers. Here, we first estimated both static (SFC) and dynamic functional connectivity (DFC) after beamforming source reconstruction using the imaginary part of the phase locking index (iPLV) and the correlation of the amplitude envelope (CorEnv). Using our approach, functional network microstates (FCμstates) were derived from the DFC and chronnectomics were computed from the evolution of FCμstates across experimental time. In both temporal scales, the reliability of network metrics (SFC), the FCμstates and the related chronnectomics were evaluated for every frequency band. Chronnectomic statistics and FCμstates were generally more reliable than node-wise static network metrics. CorEnv-based network metrics were more reproducible at the static approach. The reliability of chronnectomics have been evaluated also in a second dataset. This study encourages the analysis of MEG resting-state via DFC.
| S-EPMC6088195 | biostudies-literature
Project description:Characterization of large-scale brain networks using blood-oxygenation-level-dependent functional magnetic resonance imaging is typically based on the assumption of network stationarity across the duration of scan. Recent studies in humans have questioned this assumption by showing that within-network functional connectivity fluctuates on the order of seconds to minutes. Time-varying profiles of resting-state networks (RSNs) may relate to spontaneously shifting, electrophysiological network states and are thus mechanistically of particular importance. However, because these studies acquired data from awake subjects, the fluctuating connectivity could reflect various forms of conscious brain processing such as passive mind wandering, active monitoring, memory formation, or changes in attention and arousal during image acquisition. Here, we characterize RSN dynamics of anesthetized macaques that control for these accounts, and compare them to awake human subjects. We find that functional connectivity among nodes comprising the "oculomotor (OCM) network" strongly fluctuated over time during awake as well as anaesthetized states. For time dependent analysis with short windows (<60 s), periods of positive functional correlations alternated with prominent anticorrelations that were missed when assessed with longer time windows. Similarly, the analysis identified network nodes that transiently link to the OCM network and did not emerge in average RSN analysis. Furthermore, time-dependent analysis reliably revealed transient states of large-scale synchronization that spanned all seeds. The results illustrate that resting-state functional connectivity is not static and that RSNs can exhibit nonstationary, spontaneous relationships irrespective of conscious, cognitive processing. The findings imply that mechanistically important network information can be missed when using average functional connectivity as the single network measure.
| S-EPMC6870538 | biostudies-literature
Project description:IntroductionRecent studies related to assessing functional connectivity (FC) in resting-state functional magnetic resonance imaging have revealed that the resulting connectivity patterns exhibit considerable fluctuations (dynamic FC [dFC]). A widely applied method for quantifying dFC is the sliding window technique. According to this method, the data are divided into segments with the same length (window size) and a correlation metric is employed to assess the connectivity within these segments, whereby the window size is often empirically chosen.MethodsIn this study, we rigorously investigate the assessment of dFC using the sliding window approach. Specifically, we perform a detailed comparison between different correlation metrics, including Pearson, Spearman and Kendall correlation, Pearson and Spearman partial correlation, Mutual Information (MI), Variation of Information (VI), Kullback-Leibler divergence, Multiplication of Temporal Derivatives and Inverse Covariance.ResultsUsing test-retest datasets, we show that MI and VI yielded the most consistent results by achieving high reliability with respect to dFC estimates for different window sizes. Subsequent hypothesis testing, based on multivariate phase randomization surrogate data generation, allowed the identification of dynamic connections between the posterior cingulate cortex and regions in the frontal lobe and inferior parietal lobes, which were overall in agreement with previous studies.ConclusionsIn the case of MI and VI, a window size of at least 120 s was found to be necessary for detecting dFC for some of the previously identified dynamically connected regions.
| S-EPMC6456784 | biostudies-literature
Project description:Major depressive disorder (MDD) is characterized by abnormal resting-state functional connectivity (RSFC), especially in medial prefrontal cortical (MPFC) regions of the default network. However, prior research in MDD has not examined dynamic changes in functional connectivity as networks form, interact, and dissolve over time. We compared unmedicated individuals with MDD (n=100) to control participants (n=109) on dynamic RSFC (operationalized as SD in RSFC over a series of sliding windows) of an MPFC seed region during a resting-state functional magnetic resonance imaging scan. Among participants with MDD, we also investigated the relationship between symptom severity and RSFC. Secondary analyses probed the association between dynamic RSFC and rumination. Results showed that individuals with MDD were characterized by decreased dynamic (less variable) RSFC between MPFC and regions of parahippocampal gyrus within the default network, a pattern related to sustained positive connectivity between these regions across sliding windows. In contrast, the MDD group exhibited increased dynamic (more variable) RSFC between MPFC and regions of insula, and higher severity of depression was related to increased dynamic RSFC between MPFC and dorsolateral prefrontal cortex. These patterns of highly variable RSFC were related to greater frequency of strong positive and negative correlations in activity across sliding windows. Secondary analyses indicated that increased dynamic RSFC between MPFC and insula was related to higher levels of recent rumination. These findings provide initial evidence that depression, and ruminative thinking in depression, are related to abnormal patterns of fluctuating communication among brain systems involved in regulating attention and self-referential thinking.
| S-EPMC4869051 | biostudies-literature