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Zamani Esfahlani, F.

Publications and source records attributed to Zamani Esfahlani, F..

9 recordsLinked to original sources

Modular subgraphs in large-scale connectomes underpin spontaneous co-fluctuation "events" in mouse and human brains

Previous studies have adopted an edge-centric framework to study fine-scale dynamics in human fMRI. To date, however, no studies have applied this same framework to data collected from model organisms. Here, we analyze structural and functional imaging data from lightly anesthetized mice through an edge-centric lens. We find evidence of "bursty" dynamics and events - brief periods of high-amplitude network connectivity. Further, we show that on a per-frame basis events best explain static FC and can be divided into a series of hierarchically-related clusters. The co-fluctuation patterns associated with each centroid link distinct anatomical areas and largely adhere to the boundaries of algorithmically detected functional brain systems. We then investigate the anatomical connectivity undergirding high-amplitude co-fluctuation patterns. We find that events induce modular bipartitions of the anatomical network of inter-areal axonal projections. Finally, we replicate these same findings in a human imaging dataset. In summary, this report recapitulates in a model organism many of the same phenomena observed in previously edge-centric analyses of human imaging data. However, unlike human subjects, the murine nervous system is amenable to invasive experimental perturbations. Thus, this study sets the stage for future investigation into the causal origins of fine-scale brain dynamics and high-amplitude co-fluctuations. Moreover, the cross-species consistency of the reported findings enhances the likelihood of future translation.

neuroscience↗

System-level high-amplitude co-fluctuations

Edge time series decompose interregional correlations (functional connectivity; FC) into their time-varying contributions. Previous studies have revealed that brief, high-amplitude, and globally-defined "events" contribute disproportionately to the time-averaged FC pattern. This whole-brain view prioritizes systems that occupy vast neocortical territory, possibly obscuring extremely high-amplitude co-fluctuations that are localized to smaller brain systems. Here, we investigate local events detected at the system level, assessing their independent contributions to global events and characterizing their repertoire during resting-state and movie-watching scans. We find that, as expected, global events are more likely to occur when large brain systems exhibit events. Next, we study the co-fluctuation patterns that coincide with system events-i.e. events detected locally based on the behavior of individual brain systems. We find that although each system exhibits a distinct co-fluctuation pattern that is dissimilar from those associated with global events, the patterns can nonetheless be grouped into two broad categories, corresponding to events that coincide with sensorimotor and attention systems and, separately, association systems. We then investigate system-level events during movie-watching, discovering that the timing of events in sensorimotor and attention systems decouple, yielding reductions in co-fluctuation amplitude. Next, we show that by associating each edge with its most similar system-averaged edge time series, we recover overlapping community structure, obviating the need for applying clustering algorithms to high-dimensional edge time series. Finally, we focus on cortical responses to system-level events in subcortical areas and the cerebellum. We show that these structures coincide with spatially distributed cortical co-fluctuations, centered on prefrontal and somatosensory systems. Collectively, the findings presented here help clarify the relative contributions of large and small systems to global events, as well as their independent behavior.

neuroscience↗

Cortico-Subcortical Interactions in Overlapping Communities of Edge Functional Connectivity

Both cortical and subcortical regions can be functionally organized into networks. Regions of the basal ganglia are extensively interconnected with the cortex via reciprocal connections that relay and modulate cortical function. Here we employ an edge-centric approach, which computes co-fluctuations among region pairs in a network to investigate the role and interaction of subcortical regions with cortical systems. By clustering edges into communities, we show that cortical systems and subcortical regions couple via multiple edge communities, with hippocampus and amygdala having a distinct pattern from striatum and thalamus. We show that the edge community structure of cortical networks is highly similar to one obtained from cortical nodes when the subcortex is present in the network. Additionally, we show that the edge community profile of both cortical and subcortical nodes can be estimates solely from cortico-subcortical interactions. Finally, we used a motif analysis focusing on edge community triads where a subcortical region coupled to two cortical regions and found that two community triads where one community couples the subcortex to the cortex were overrepresented. In summary, our results show organized coupling of the subcortex to the cortex that may play a role in cortical organization of primary sensorimotor/attention and heteromodal systems and puts forth the motif analysis of edge community triads as a promising method for investigation of communication patterns in networks.

neuroscience↗

Edge-centric analysis of time-varying functional brain networks with applications in autism spectrum disorder

The interaction between brain regions changes over time, which can be characterized using time-varying functional connectivity (tvFC). The common approach to estimate tvFC uses sliding windows and offers limited temporal resolution. An alternative method is to use the recently proposed edge-centric approach, which enables the tracking of moment-to-moment changes in co-fluctuation patterns between pairs of brain regions. Here, we first examined the dynamic features of edge time series and compared them to those in the sliding window tvFC (sw-tvFC). Then, we used edge time series to compare subjects with autism spectrum disorder (ASD) and healthy controls (CN). Our results indicate that relative to sw-tvFC, edge time series captured rapid and bursty network-level fluctuations that synchronize across subjects during movie-watching. The results from the second part of the study suggested that the magnitude of peak amplitude in the collective co-fluctuations of brain regions (estimated as root sum square (RSS) of edge time series) is similar in CN and ASD. However, the trough-to-trough duration in RSS signal is greater in ASD, compared to CN. Furthermore, an edge-wise comparison of high-amplitude co-fluctuations showed that the within-network edges exhibited greater magnitude fluctuations in CN. Our findings suggest that high-amplitude co-fluctuations captured by edge time series provide details about the disruption of functional brain dynamics that could potentially be used in developing new biomarkers of mental disorders.

neuroscience↗

Subject identification using edge-centric functional connectivity

Group-level studies do not capture individual differences in network organization, an important prerequisite for understanding neural substrates shaping behavior and for developing interventions in clinical conditions. Recent studies have employed "fingerprinting" analyses on functional connectivity to identify subjects idiosyncratic features. Here, we develop a complementary approach based on an edge-centric model of functional connectivity, which focuses on the co-fluctuations of edges. We first show whole-brain edge functional connectivity (eFC) to be a robust substrate that improves identifiability over nodal FC (nFC) across different datasets and parcellations. Next, we characterized subjects identifiability at different spatial scales, from single nodes to the level of functional systems and clusters using k-means clustering. Across spatial scales, we find that heteromodal brain regions exhibit consistently greater identifiability than unimodal, sensorimotor, and limbic regions. Lastly, we show that identifiability can be further improved by reconstructing eFC using specific subsets of its principal components. In summary, our results highlight the utility of the edge-centric network model for capturing meaningful subject-specific features and sets the stage for future investigations into individual differences using edge-centric models.

neuroscience↗

The diversity and multiplexity of edge communities within and between brain systems

The human brain is composed of regions that can be grouped into functionally specialized systems. These systems transiently couple and decouple across time to support complex cognitive processes. Recently, we proposed an edge-centric model of brain networks whose elements can be clustered to reveal communities of connections whose co-fluctuations are correlated across time. It remains unclear, however, how these co-fluctuation patterns relate to traditionally-defined brain systems. Here, we address this question using data from the Midnight Scan Club. We show that edge communities transcend traditional definitions of brain systems, forming a multiplexed network in which all pairs of brain systems are linked to one another by at least two distinct edge communities. Mapping edge communities back to individual brain regions and deriving a novel distance metric to describe the similarity of regions "edge community profiles", we then demonstrate that the within-system similarity of profiles is heterogeneous across systems. Specifically, we find that heteromodal association areas exhibit significantly greater diversity of edge communities than primary sensory systems. Next, we cluster the entire cerebral cortex according to the similarity of regions edge community profiles, revealing systematic differences between traditionally-defined systems and the detected clusters. Specifically, we find that regions in heteromodal systems exhibit dissimilar edge community profiles and are more likely to form their own clusters. Finally, we show show that edge communities are highly personalized and can be used to identify individual subjects. Collectively, our work reveals the pervasive overlap of edge communities across the cerebral cortex and characterizes their relationship with the brains system level architecture. Our work provides clear pathways for future research using edge-centric brain networks to investigate individual differences in behavior, development, and disease.

neuroscience↗

Edge-centric functional network representations of human cerebral cortex reveal overlapping system-level architecture

Network neuroscience has relied on a node-centric network model in which cells, populations, and regions are linked to one another via anatomical or functional connections. This model cannot account for interactions of edges with one another. Here, we develop an edge-centric network model, which generates the novel constructs of \"edge time series\" and \"edge functional connectivity\" (eFC). Using network analysis, we show that at rest eFC is consistent across datasets and reproducible within the same individual over multiple scan sessions. We demonstrate that clustering eFC yields communities of edges that naturally divide the brain into overlapping clusters, with regions in sensorimotor and attentional networks exhibiting the greatest levels of overlap. We go on to show that eFC is systematically and consistently modulated by variation in sensory input. In future work, the edge-centric approach could be used to map the connectional architecture of brain circuits and for the development of brain-based biomarkers of disease and development.

neuroscience↗

Temporal fluctuations in the brain’s modular architecture during movie-watching

Brain networks are flexible and reconfigure over time to support ongoing cognitive processes. However, tracking statistically meaningful reconfigurations across time has proven difficult. This has to do largely with issues related to sampling variability, making instantaneous estimation of network organization difficult, along with increased reliance on task-free (cognitively unconstrained) experimental paradigms, limiting the ability to interpret the origin of changes in network structure over time. Here, we address these challenges using time-varying network analysis in conjunction with a naturalistic viewing paradigm. Specifically, we developed a measure of inter-subject network similarity and used this measure as a coincidence filter to identify synchronous fluctuations in network organization across individuals. Applied to movie-watching data, we found that periods of high inter-subject similarity coincided with reductions in network modularity and increased connectivity between cognitive systems. In contrast, low inter-subject similarity was associated with increased system segregation and more rest-like architectures. We then used a data-driven approach to uncover clusters of functional connections that follow similar trajectories over time and are more strongly correlated during movie-watching than at rest. Finally, we show that synchronous fluctuations in network architecture over time can be linked to a subset of features in the movie. Our findings link dynamic fluctuations in network integration and segregation to patterns of intersubject similarity, and suggest that moment-to-moment fluctuations in FC reflect shared cognitive processing across individuals.

neuroscience↗

Space-independent community and hub structure of functional brain networks

Coordinated brain activity reflects underlying cognitive processes and can be modeled as a network of inter-regional functional connections. The most costly connections in the network are long-distance correlations that, in the absence of underlying structural connections, are maintained by sustained energetic inputs. Here, we present a spatial modeling approach that amplifies contributions made by long-distance functional connections to whole-brain network architecture, while simultaneously suppressing contributions made by short-range connections. We use this method to characterize the long-distance architecture of functional networks and to identify aspects of community and hub structure that are driven by long-distance correlations and that, we argue, are of greater functional significance. We find that based only on patterns of long-distance connectivity, primary sensory cortices occupy increasingly central positions and appear more \"hub-like\". Additionally, we show that the community structure of long-distance connections spans multiple topological levels and differs from the community structure detected in networks that include both short-range and long-distance connections. In summary, these findings highlight the complex relationship between the brains physical layout and its functional architecture. The results presented here inform future analyses of community structure and network hubs in health, across development, and in the case of neuropsychiatric disorders.

neuroscience↗