arXiv subjects

Richard F. Betzel

Publications and source records attributed to Richard F. Betzel.

At least 19 recordsLinked to original sources

arXiv2025

Quantifying the compressibility of the human brain

In the human brain, the allowed patterns of activity are constrained by the correlations between brain regions. Yet it remains unclear which correlations -- and how many -- are needed to predict large-scale neural activity. Here, we present an information-theoretic framework to identify the most important correlations, which provide the most accurate predictions of neural states. Applying our framework to cortical activity in humans, we discover that the vast majority of variance in activity is explained by a small number of correlations. This means that the brain is highly compressible: only a sparse network of correlations is needed to predict large-scale activity. We find that this compressibility is strikingly consistent across different individuals and cognitive tasks, and that, counterintuitively, the most important correlations are not necessarily the strongest. Together, these results suggest that nearly all correlations are not needed to predict neural activity, and we provide the tools to uncover the key correlations that are.

physics.bio-ph↗

arXiv2024

Modular Boundaries in Recurrent Neural Networks

Recent theoretical and experimental work in neuroscience has focused on the representational and dynamical character of neural manifolds --subspaces in neural activity space wherein many neurons coactivate. Importantly, neural populations studied under this "neural manifold hypothesis" are continuous and not cleanly divided into separate neural populations. This perspective clashes with the "modular hypothesis" of brain organization, wherein neural elements maintain an "all-or-nothing" affiliation with modules. In line with this modular hypothesis, recent research on recurrent neural networks suggests that multi-task networks become modular across training, such that different modules specialize for task-general dynamical motifs. If the modular hypothesis is true, then it would be important to use a dimensionality reduction technique that captures modular structure. Here, we investigate the features of such a method. We leverage RNNs as a model system to study the character of modular neural populations, using a community detection method from network science known as modularity maximization to partition neurons into distinct modules. These partitions allow us to ask the following question: do these modular boundaries matter to the system? ...

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arXiv2022

High-Accuracy Machine Learning Techniques for Functional Connectome Fingerprinting and Cognitive State Decoding

The human brain is a complex network comprised of functionally and anatomically interconnected brain regions. A growing number of studies have suggested that empirical estimates of brain networks may be useful for discovery of biomarkers of disease and cognitive state. A prerequisite for realizing this aim, however, is that brain networks also serve as reliable markers of an individual. Here, using Human Connectome Project data, we build upon recent studies examining brain-based fingerprints of individual subjects and cognitive states based on cognitively-demanding tasks that assess, for example, working memory, theory of mind, and motor function. Our approach achieves accuracy of up to 99\% for both identification of the subject of an fMRI scan, and for classification of the cognitive state of a previously-unseen subject in a scan. More broadly, we explore the accuracy and reliability of five different machine learning techniques on subject fingerprinting and cognitive state decoding objectives, using functional connectivity data from fMRI scans of a high number of subjects (865) across a number of cognitive states (8). These results represent an advance on existing techniques for functional connectivity-based brain fingerprinting and state decoding. Additionally, 16 different pre-processing pipelines are compared in order to characterize the effects of different aspects of the production of functional connectomes (FCs) on the accuracy of subject and task classification, and to identify possible confounds.

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arXiv2021

Diurnal variations of resting-state fMRI data: A graph-based analysis

Circadian rhythms synchronize a variety of physiological processes ranging from neural activity and hormone secretion to sleep cycles and feeding habits. Despite significant diurnal variation, time-of-day (TOD) is rarely recorded or analyzed in human brain research. Moreover, sleep-wake patterns, diurnal preferences, and daytime alertness vary across individuals, known as sleep chronotypes. Here, we performed graph-theory network analysis on resting-state functional MRI (rs-fMRI) data to explore topological differences in whole-brain functional networks between morning and evening sessions (TOD effect), and between extreme morning-type and evening-type chronotypes. To that end, 62 individuals (31 extreme morning, 31 evening-type) underwent two fMRI sessions: about 1 hour after the wake-up time (morning), and 10 hours thereafter, scheduled in accord with their declared habitual sleep-wake pattern. TOD significantly altered functional connectivity (FC) patterns, but there was no significant difference in chronotypic categories. Compared to the morning session, we found relatively increased small-worldness, modularity, assortativity, and synchronization in the evening session, indicating more efficient functional topology. Local measures were changed during the day predominantly across the areas involved in somatomotor, ventral attention, as well as default mode networks. Also, connectivity and hub analyses showed that the somatomotor, ventral attention, and visual networks are the most densely-connected brain areas in both sessions, respectively, with the first being more active in the evening session and the two latter in the morning session. Collectively, these findings suggest TOD can impact classic analyses used in human neuroimaging such as functional connectivity, and should be recorded and included in the analysis of functional neuroimaging data.

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arXiv2021

Modularity maximization as a flexible and generic framework for brain network exploratory analysis

The modular structure of brain networks supports specialized information processing, complex dynamics, and cost-efficient spatial embedding. Inter-individual variation in modular structure has been linked to differences in performance, disease, and development. There exist many data-driven methods for detecting and comparing modular structure, the most popular of which is modularity maximization. Although modularity maximization is a general framework that can be modified and reparamaterized to address domain-specific research questions, its application to neuroscientific datasets has, thus far, been narrow. Here, we highlight several strategies in which the ``out-of-the-box'' version of modularity maximization can be extended to address questions specific to neuroscience. First, we present approaches for detecting ``space-independent'' modules and for applying modularity maximization to signed matrices. Next, we show that the modularity maximization frame is well-suited for detecting task- and condition-specific modules. Finally, we highlight the role of multi-layer models in detecting and tracking modules across time, tasks, subjects, and modalities. In summary, modularity maximization is a flexible and general framework that can be adapted to detect modular structure resulting from a wide range of hypotheses. This article highlights opens multiple frontiers for future research and applications.

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arXiv2021

Edges in Brain Networks: Contributions to Models of Structure and Function

Network models describe the brain as sets of nodes and edges that represent its distributed organization. So far, most discoveries in network neuroscience have prioritized insights that highlight distinct groupings and specialized functional contributions of network nodes. Importantly, these functional contributions are determined and expressed by the web of their interrelationships, formed by network edges. Here, we underscore the important contributions made by brain network edges for understanding distributed brain organization. Different types of edges represent different types of relationships, including connectivity and similarity among nodes. Adopting a specific definition of edges can fundamentally alter how we analyze and interpret a brain network. Furthermore, edges can associate into collectives and higher-order arrangements, describe time series, and form edge communities that provide insights into brain network topology complementary to the traditional node-centric perspective. Focusing on the edges, and the higher-order or dynamic information they can provide, discloses previously underappreciated aspects of structural and functional network organization.

q-bio.NC↗

arXiv2020

Community detection in network neuroscience

Many real-world networks, including nervous systems, exhibit meso-scale structure. This means that their elements can be grouped into meaningful sub-networks. In general, these sub-networks are unknown ahead of time and must be "discovered" algorithmically using community detection methods. In this article, we review evidence that nervous systems exhibit meso-scale structure in the form of communities, clusters, and modules. We also provide a set of guidelines to assist users in applying community detection methods to their own network data. These guidelines focus on the method of modularity maximization but, in many cases, are general and applicable to other techniques.

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arXiv2019

Temporal sequences of brain activity at rest are constrained by white matter structure and modulated by cognitive demands

A diverse white matter network and finely tuned neuronal membrane properties allow the brain to transition seamlessly between cognitive states. However, it remains unclear how static structural connections guide the temporal progression of large-scale brain activity patterns in different cognitive states. Here, we analyze the brain's trajectories through a high-dimensional activity space at the level of single time point activity patterns from functional magnetic resonance imaging data acquired during passive visual fixation (rest) and an n-back working memory task. We find that specific state space trajectories, which represent temporal sequences of brain activity, are modulated by cognitive load and related to task performance. Using diffusion-weighted imaging acquired from the same subjects, we use tools from network control theory to show that linear spread of activity along white matter connections constrains the brain's state space trajectories at rest. Additionally, accounting for stimulus-driven visual inputs explains the different trajectories taken during the n-back task. We also used models of network rewiring to show that these findings are the result of non-trivial geometric and topological properties of white matter architecture. Finally, we examine associations between age and time-resolved brain state dynamics, revealing new insights into functional changes in the default mode and executive control networks. Overall, these results elucidate the structural underpinnings of cognitively and developmentally relevant spatiotemporal brain dynamics.

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arXiv2019

Brain state stability during working memory is explained by network control theory, modulated by dopamine D1/D2 receptor function, and diminished in schizophrenia

Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory entails brainwide switching between activity states. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Schizophrenia patients show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations.

q-bio.NC↗

arXiv2018

Stability of spontaneous, correlated activity in mouse auditory cortex

Neural systems can be modeled as networks of functionally connected neural elements. The resulting network can be analyzed using mathematical tools from network science and graph theory to quantify the system's topological organization and to better understand its function. While the network-based approach is common in the analysis of large-scale neural systems probed by non-invasive neuroimaging, few studies have used network science to study the organization of networks reconstructed at the cellular level, and thus many very basic and fundamental questions remain unanswered. Here, we used two-photon calcium imaging to record spontaneous activity from the same set of cells in mouse auditory cortex over the course of several weeks. We reconstruct functional networks in which cells are linked to one another by edges weighted according to the correlation of their fluorescence traces. We show that the networks exhibit modular structure across multiple topological scales and that these multi-scale modules unfold as part of a hierarchy. We also show that, on average, network architecture becomes increasingly dissimilar over time, with similarity decaying monotonically with the distance (in time) between sessions. Finally, we show that a small fraction of cells maintain strongly-correlated activity over multiple days, forming a stable temporal core surrounded by a fluctuating and variable periphery. Our work provides a careful methodological blueprint for future studies of spontaneous activity measured by two-photon calcium imaging using cutting-edge computational methods and machine learning algorithms informed by explicit graphical models from network science. The methods are easily extended to additional datasets, opening the possibility of studying cellular level network organization of neural systems and how that organization is modulated by stimuli or altered in models of disease.

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arXiv2018

Genetic and Neuroanatomical Support for Functional Brain Network Dynamics in Epilepsy

Focal epilepsy is a devastating neurological disorder that affects an overwhelming number of patients worldwide, many of whom prove resistant to medication. The efficacy of current innovative technologies for the treatment of these patients has been stalled by the lack of accurate and effective methods to fuse multimodal neuroimaging data to map anatomical targets driving seizure dynamics. Here we propose a parsimonious model that explains how large-scale anatomical networks and shared genetic constraints shape inter-regional communication in focal epilepsy. In extensive ECoG recordings acquired from a group of patients with medically refractory focal-onset epilepsy, we find that ictal and preictal functional brain network dynamics can be accurately predicted from features of brain anatomy and geometry, patterns of white matter connectivity, and constraints complicit in patterns of gene coexpression, all of which are conserved across healthy adult populations. Moreover, we uncover evidence that markers of non-conserved architecture, potentially driven by idiosyncratic pathology of single subjects, are most prevalent in high frequency ictal dynamics and low frequency preictal dynamics. Finally, we find that ictal dynamics are better predicted by white matter features and more poorly predicted by geometry and genetic constraints than preictal dynamics, suggesting that the functional brain network dynamics manifest in seizures rely on - and may directly propagate along - underlying white matter structure that is largely conserved across humans. Broadly, our work offers insights into the generic architectural principles of the human brain that impact seizure dynamics, and could be extended to further our understanding, models, and predictions of subject-level pathology and response to intervention.

q-bio.NC↗

arXiv2017

The specificity and robustness of long-distance connections in weighted, interareal connectomes

Brain areas' functional repertoires are shaped by their incoming and outgoing structural connections. In empirically measured networks, most connections are short, reflecting spatial and energetic constraints. Nonetheless, a small number of connections span long distances, consistent with the notion that the functionality of these connections must outweigh their cost. While the precise function of these long-distance connections is not known, the leading hypothesis is that they act to reduce the topological distance between brain areas and facilitate efficient interareal communication. However, this hypothesis implies a non-specificity of long-distance connections that we contend is unlikely. Instead, we propose that long-distance connections serve to diversify brain areas' inputs and outputs, thereby promoting complex dynamics. Through analysis of five interareal network datasets, we show that long-distance connections play only minor roles in reducing average interareal topological distance. In contrast, areas' long-distance and short-range neighbors exhibit marked differences in their connectivity profiles, suggesting that long-distance connections enhance dissimilarity between regional inputs and outputs. Next, we show that -- in isolation -- areas' long-distance connectivity profiles exhibit non-random levels of similarity, suggesting that the communication pathways formed by long connections exhibit redundancies that may serve to promote robustness. Finally, we use a linearization of Wilson-Cowan dynamics to simulate the covariance structure of neural activity and show that in the absence of long-distance connections, a common measure of functional diversity decreases. Collectively, our findings suggest that long-distance connections are necessary for supporting diverse and complex brain dynamics.

q-bio.NC↗

arXiv2017

Generative Models for Network Neuroscience: Prospects and Promise

Network neuroscience is the emerging discipline concerned with investigating the complex patterns of interconnections found in neural systems, and to identify principles with which to understand them. Within this discipline, one particularly powerful approach is network generative modeling, in which wiring rules are algorithmically implemented to produce synthetic network architectures with the same properties as observed in empirical network data. Successful models can highlight the principles by which a network is organized and potentially uncover the mechanisms by which it grows and develops. Here we review the prospects and promise of generative models for network neuroscience. We begin with a primer on network generative models, with a discussion of compressibility and predictability, utility in intuiting mechanisms, and a short history on their use in network science broadly. We then discuss generative models in practice and application, paying particular attention to the critical need for cross-validation. Next, we review generative models of biological neural networks, both at the cellular and large-scale level, and across a variety of species including \emph{C. elegans}, \emph{Drosophila}, mouse, rat, cat, macaque, and human. We offer a careful treatment of a few relevant distinctions, including differences between generative models and null models, sufficiency and redundancy, inferring and claiming mechanism, and functional and structural connectivity. We close with a discussion of future directions, outlining exciting frontiers both in empirical data collection efforts as well as in method and theory development that, together, further the utility of the generative network modeling approach for network neuroscience.

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arXiv2017

Fluctuations between high- and low-modularity topology in time-resolved functional connectivity

Modularity is an important topological attribute for functional brain networks. Recent studies have reported that modularity of functional networks varies not only across individuals being related to demographics and cognitive performance, but also within individuals co-occurring with fluctuations in network properties of functional connectivity, estimated over short time intervals. However, characteristics of these time-resolved functional networks during periods of high and low modularity have remained largely unexplored. In this study we investigate spatiotemporal properties of time-resolved networks in the high and low modularity periods during rest, with a particular focus on their spatial connectivity patterns, temporal homogeneity and test-retest reliability. We show that spatial connectivity patterns of time-resolved networks in the high and low modularity periods are represented by increased and decreased dissociation of the default mode network module from task-positive network modules, respectively. We also find that the instances of time-resolved functional connectivity sampled from within the high (low) modularity period are relatively homogeneous (heterogeneous) over time, indicating that during the low modularity period the default mode network interacts with other networks in a variable manner. We confirmed that the occurrence of the high and low modularity periods varies across individuals with moderate inter-session test-retest reliability and that it is correlated with previously-reported individual differences in the modularity of functional connectivity estimated over longer timescales. Our findings illustrate how time-resolved functional networks are spatiotemporally organized during periods of high and low modularity, allowing one to trace individual differences in long-timescale modularity to the variable occurrence of network configurations at shorter timescales.

q-bio.NC↗

arXiv2017

Inter-regional ECoG correlations predicted by communication dynamics, geometry, and correlated gene expression

Electrocorticography (ECoG) provides direct measurements of synchronized postsynaptic potentials at the exposed cortical surface. Patterns of signal covariance across ECoG sensors have been associated with diverse cognitive functions and remain a critical marker of seizure onset, progression, and termination. Yet, a systems level understanding of these patterns (or networks) has remained elusive, in part due to variable electrode placement and sparse cortical coverage. Here, we address these challenges by constructing inter-regional ECoG networks from multi-subject recordings, demonstrate similarities between these networks and those constructed from blood-oxygen-level-dependent signal in functional magnetic resonance imaging, and predict network topology from anatomical connectivity, interregional distance, and correlated gene expression patterns. Our models accurately predict out-of-sample ECoG networks and perform well even when fit to data from individual subjects, suggesting shared organizing principles across persons. In addition, we identify a set of genes whose brain-wide co-expression is highly correlated with ECoG network organization. Using gene ontology analysis, we show that these same genes are enriched for membrane and ion channel maintenance and function, suggesting a molecular underpinning of ECoG connectivity. Our findings provide fundamental understanding of the factors that influence interregional ECoG networks, and open the possibility for predictive modeling of surgical outcomes in disease.

q-bio.NC↗

arXiv2017

Benchmarking measures of network controllability on canonical graph models

Many real-world systems are composed of many individual components that interact with one another in a complex pattern to produce diverse behaviors. Understanding how to intervene in these systems to guide behaviors is critically important to facilitate new discoveries and therapies in systems biology and neuroscience. A promising approach to optimizing interventions in complex systems is network control theory, an emerging conceptual framework and associated mathematics to understand how targeted input to nodes in a network system can predictably alter system dynamics. While network control theory is currently being applied to real-world data, the practical performance of these measures on simple networks with pre-specified structure is not well understood. In this study, we benchmark measures of network controllability on canonical graph models, providing an intuition for how control strategy, graph topology, and edge weight distribution mutually depend on one another. Our numerical studies motivate future analytical efforts to gain a mechanistic understanding of the relationship between graph topology and control, as well as efforts to design networks with specific control profiles.

physics.soc-ph↗

arXiv2017

Diversity of meso-scale architecture in human and non-human connectomes

The brain's functional diversity is reflected in the meso-scale architecture of its connectome, i.e. its division into clusters and communities of topologically-related brain regions. The dominant view, and one that is reinforced by current analysis techniques, is that communities are strictly assortative and segregated from one another, purportedly for the purpose of carrying out specialized information processing. Such a view, however, precludes the possibility of non-assortative communities that could engender a richer functional repertoire by allowing for a more complex set of inter-community interactions. Here, we use weighted stochastic blockmodels to uncover the meso-scale architecture of \emph{Drosophila}, mouse, rat, macaque, and human connectomes. We confirm that while many communities are assortative, others form core-periphery and disassortative structures, which in the human better recapitulate observed patterns of functional connectivity and in the mouse better recapitulate observed patterns of gene co-expression than other community detection techniques. We define a set of network measures for quantifying the diversity of community types in which brain regions participate. Finally, we show that diversity is peaked in control and subcortical systems in humans, and that individual differences in diversity within those systems predicts cognitive performance on Stroop and Navon tasks. In summary, our report paints a more diverse portrait of connectome meso-scale structure and demonstrates its relevance for cognitive performance.

q-bio.NC↗

arXiv2017

Optimal Trajectories of Brain State Transitions

The complexity of neural dynamics stems in part from the complexity of the underlying anatomy. Yet how the organization of white matter architecture constrains how the brain transitions from one cognitive state to another remains unknown. Here we address this question from a computational perspective by defining a brain state as a pattern of activity across brain regions. Drawing on recent advances in network control theory, we model the underlying mechanisms of brain state transitions as elicited by the collective control of region sets. Specifically, we examine how the brain moves from a specified initial state (characterized by high activity in the default mode) to a specified target state (characterized by high activity in primary sensorimotor cortex) in finite time. Across all state transitions, we observe that the supramarginal gyrus and the inferior parietal lobule consistently acted as efficient, low energy control hubs, consistent with their strong anatomical connections to key input areas of sensorimotor cortex. Importantly, both these and other regions in the fronto-parietal, cingulo-opercular, and attention systems are poised to affect a broad array of state transitions that cannot easily be classified by traditional notions of control common in the engineering literature. This theoretical versatility comes with a vulnerability to injury. In patients with mild traumatic brain injury, we observe a loss of specificity in putative control processes, suggesting greater susceptibility to damage-induced noise in neurophysiological activity. These results offer fundamentally new insights into the mechanisms driving brain state transitions in healthy cognition and their alteration following injury.

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