skip to main content

Title: Dynamic expression of brain functional systems disclosed by fine-scale analysis of edge time series
Abstract Functional connectivity (FC) describes the statistical dependence between neuronal populations or brain regions in resting-state fMRI studies and is commonly estimated as the Pearson correlation of time courses. Clustering or community detection reveals densely coupled sets of regions constituting resting-state networks or functional systems. These systems manifest most clearly when FC is sampled over longer epochs but appear to fluctuate on shorter timescales. Here, we propose a new approach to reveal temporal fluctuations in neuronal time series. Unwrapping FC signal correlations yields pairwise co-fluctuation time series, one for each node pair or edge, and allows tracking of fine-scale dynamics across the network. Co-fluctuations partition the network, at each time step, into exactly two communities. Sampled over time, the overlay of these bipartitions, a binary decomposition of the original time series, very closely approximates functional connectivity. Bipartitions exhibit characteristic spatiotemporal patterns that are reproducible across participants and imaging runs, capture individual differences, and disclose fine-scale temporal expression of functional systems. Our findings document that functional systems appear transiently and intermittently, and that FC results from the overlay of many variable instances of system expression. Potential applications of this decomposition of functional connectivity into a set of binary patterns are discussed.
; ; ; ;
Award ID(s):
Publication Date:
Journal Name:
Network Neuroscience
Page Range or eLocation-ID:
405 to 433
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Background There is growing evidence indicating that a number of functional connectivity networks are disrupted at each stage of the full clinical Alzheimer’s disease spectrum. Such differences are also detectable in cognitive normal (CN) carrying mutations of AD risk genes, suggesting a substantial relationship between genetics and AD-altered functional brain networks. However, direct genetic effect on functional connectivity networks has not been measured. Methods Leveraging existing AD functional connectivity studies collected in NeuroSynth, we performed a meta-analysis to identify two sets of brain regions: ones with altered functional connectivity in resting state network and ones without. Then with the brain-wide gene expression data in the Allen Human Brain Atlas, we applied a new biclustering method to identify a set of genes with differential co-expression patterns between these two set of brain regions. Results Differential co-expression analysis using biclustering method led to a subset of 38 genes which showed distinctive co-expression patterns between AD-related and non AD-related brain regions in default mode network. More specifically, we observed 4 sub-clusters with noticeable co-expression difference, where the difference in correlations is above 0.5 on average. Conclusions This work applies a new biclustering method to search for a subset of genes with alteredmore »co-expression patterns in AD-related default mode network regions. Compared with traditional differential expression analysis, differential co-expression analysis yielded many more significant hits with extra insights into the wiring mechanism between genes. Particularly, the differential co-expression pattern was observed between two sets of genes, suggesting potential upstream genetic regulators in AD development.« less
  2. Abstract

    Spontaneous infra-slow (<0.1 Hz) fluctuations in functional magnetic resonance imaging (fMRI) signals are temporally correlated within large-scale functional brain networks, motivating their use for mapping systems-level brain organization. However, recent electrophysiological and hemodynamic evidence suggest state-dependent propagation of infra-slow fluctuations, implying a functional role for ongoing infra-slow activity. Crucially, the study of infra-slow temporal lag structure has thus far been limited to large groups, as analyzing propagation delays requires extensive data averaging to overcome sampling variability. Here, we use resting-state fMRI data from 11 extensively-sampled individuals to characterize lag structure at the individual level. In addition to stable individual-specific features, we find spatiotemporal topographies in each subject similar to the group average. Notably, we find a set of early regions that are common to all individuals, are preferentially positioned proximal to multiple functional networks, and overlap with brain regions known to respond to diverse behavioral tasks—altogether consistent with a hypothesized ability to broadly influence cortical excitability. Our findings suggest that, like correlation structure, temporal lag structure is a fundamental organizational property of resting-state infra-slow activity.

  3. Abstract Neural activity coordinated across different scales from neuronal circuits to large-scale brain networks gives rise to complex cognitive functions. Bridging the gap between micro- and macro-scale processes, we present a novel framework based on the maximum entropy model to infer a hybrid resting state structural connectome, representing functional interactions constrained by structural connectivity. We demonstrate that the structurally informed network outperforms the unconstrained model in simulating brain dynamics; wherein by constraining the inference model with the network structure we may improve the estimation of pairwise BOLD signal interactions. Further, we simulate brain network dynamics using Monte Carlo simulations with the new hybrid connectome to probe connectome-level differences in excitation-inhibition balance between apolipoprotein E (APOE)-ε4 carriers and noncarriers. Our results reveal sex differences among APOE-ε4 carriers in functional dynamics at criticality; specifically, female carriers appear to exhibit a lower tolerance to network disruptions resulting from increased excitatory interactions. In sum, the new multimodal network explored here enables analysis of brain dynamics through the integration of structure and function, providing insight into the complex interactions underlying neural activity such as the balance of excitation and inhibition.
  4. Resting-state functional magnetic resonance imaging (rsfMRI) has become a widely used approach for detecting subtle differences in functional brain fluctuations in various studies of the healthy and disordered brain. Such studies are often based on temporal functional connectivity (i.e., the correlation between time courses derived from regions or networks within the fMRI data). While being successful for a number of tasks, temporal connectivity does not fully leverage the available spatial information. In this research study, we present a new perspective on spatial functional connectivity, which involves learning patterns of spatial coupling among brain networks by utilizing recent advances in deep learning as well as the contrastive learning framework. We show that we can learn domain-specific mappings of brain networks that can, in turn, be used to characterize differences between schizophrenia patients and control. Furthermore, we show that the coupling of intradomain networks in the controls is stronger than in patients suffering from the disorder. We also evaluate the coupling among networks of different domains and find various patterns of stronger or weaker coupling among certain domains, which provide additional insights about the brain.
  5. Abstract

    Human brains experience whole-brain anatomic and functional changes throughout the lifespan. Age-related whole-brain network changes have been studied with functional magnetic resonance imaging (fMRI) to determine their low-frequency spatial and temporal characteristics. However, little is known about age-related changes in whole-brain fast dynamics at the scale of neuronal events. The present study investigated age-related whole-brain dynamics in resting-state electroencephalography (EEG) signals from 73 healthy participants from 6 to 65 years old via characterizing transient neuronal coactivations at a resolution of tens of milliseconds. These uncovered transient patterns suggest fluctuating brain states at different energy levels of global activations. Our results indicate that with increasing age, shorter lifetimes and more occurrences were observed in the brain states that show the global high activations and more consecutive visits to the global highest-activation brain state. There were also reduced transitional steps during consecutive visits to the global lowest-activation brain state. These age-related effects suggest reduced stability and increased fluctuations when visiting high-energy brain states and with a bias toward staying low-energy brain states. These age-related whole-brain dynamics changes are further supported by changes observed in classic alpha and beta power, suggesting its promising applications in examining the effect of normal healthy brain aging,more »brain development, and brain disease.

    « less