Network Neuroscience Research Articles

Brain network mapping and glioma pathophysiology.

Adult diffuse gliomas are among the most difficult brain disorders to treat in part due to a lack of clarity regarding the anatomical origins and mechanisms of migration of the tumours. While the importance of studying networks of glioma spread has been recognized for at least 80 years, the ability to carry out such investigations in humans has emerged only recently. Here, we comprehensively review the fields of brain network mapping and glioma biology to provide a primer for investigators interested in merging these areas of inquiry for the purposes of translational research. Specifically, we trace the historical development of ideas in both brain network mapping and glioma biology, highlighting studies that explore clinical applications of network neuroscience, cells-of-origin of diffuse glioma and glioma-neuronal interactions. We discuss recent research that has merged neuro-oncology and network neuroscience, finding that the spatial distribution patterns of gliomas follow intrinsic functional and structural brain networks. Ultimately, we call for more contributions from network neuroimaging to realize the translational potential of cancer neuroscience.

Comparing models of information transfer in the structural brain network and their relationship to functional connectivity: diffusion versus shortest path routing

The relationship between structural and functional connectivity in the human brain is a core question in network neuroscience, and a topic of paramount importance to our ability to meaningfully describe and predict functional outcomes. Graph theory has been used to produce measures based on the structural connectivity network that are related to functional connectivity. These measures are commonly based on either the shortest path routing model or the diffusion model, which carry distinct assumptions about how information is transferred through the network. Unlike shortest path routing, which assumes the most efficient path is always known, the diffusion model makes no such assumption, and lets information diffuse in parallel based on the number of connections to other regions. Past research has also developed hybrid measures that use concepts from both models, which have better predicted functional connectivity from structural connectivity than the shortest path length alone. We examined the extent to which each of these models can account for the structure–function relationship of interest using graph theory measures that are exclusively based on each model. This analysis was performed on multiple parcellations of the Human Connectome Project using multiple approaches, which all converged on the same finding. We found that the diffusion model accounts for much more variance in functional connectivity than the shortest path routing model, suggesting that the diffusion model is better suited to describing the structure–function relationship in the human brain at the macroscale.

The dynamic brain-network model of PTSD

The brain is a highly complex system whose functioning is critical for our interaction with the world. Neural elements, from single cells to brain systems, constantly fluctuate in their dynamics, accompanying the plethora of possible exchanges between our environment and ourselves. However, sometimes things go awry. An unfortunate example is post-traumatic stress disorder (PTSD), a debilitating clinical condition that can appear after exposure to a threatening life event. In this work, using complexity as a framework, we aim to introduce the dynamic brain network model of PTSD. We hope this model will allow the generation of novel specific hypotheses concerning brain organization and dynamics in PTSD research. We first introduce how the network framework complements the localizationist approach centered in specific brain regions or subsets of brain regions, with a whole brain approach considering brain regions' dynamic relationships. Then, we review key concepts in network neuroscience, focusing on the importance of the network topology and dynamics to understand the organizational principles of the brain, that is, functional segregation and integration. In the third part, we apply this knowledge to describe the possible trajectories conducting a brain system to present PTSD alterations. Accordingly, we introduce the Dynamic Brain Network Model (DBNM) of PTSD, a concrete framework built on the network approach and resilience theory to study the transition of a brain network from state 1 (e.g., before the traumatic event) to state 2 (e.g., after the traumatic event). To conclude, we provide a summary of metrics for quantifying elements on the DBNM and its potential use in computational models of PTSD.

The topology, stability, and instability of learning-induced brain network repertoires in schizophrenia.

There is a paucity of graph theoretic methods applied to task-based data in schizophrenia (SCZ). Tasks are useful for modulating brain network dynamics, and topology. Understanding how changes in task conditions impact inter-group differences in topology can elucidate unstable network characteristics in SCZ. Here, in a group of patients and healthy controls (n = 59 total, 32 SCZ), we used an associative learning task with four distinct conditions (Memory Formation, Post-Encoding Consolidation, Memory Retrieval, and Post-Retrieval Consolidation) to induce network dynamics. From the acquired fMRI time series data, betweenness centrality (BC), a metric of a node's integrative value was used to summarize network topology in each condition. Patients showed (a) differences in BC across multiple nodes and conditions; (b) decreased BC in more integrative nodes, but increased BC in less integrative nodes; (c) discordant node ranks in each of the conditions; and (d) complex patterns of stability and instability of node ranks across conditions. These analyses reveal that task conditions induce highly variegated patterns of network dys-organization in SCZ. We suggest that the dys-connection syndrome that is schizophrenia, is a contextually evoked process, and that the tools of network neuroscience should be oriented toward elucidating the limits of this dys-connection.

Human motor sequence learning drives transient changes in network topology and hippocampal connectivity early during memory consolidation.

In the last decade, the exclusive role of the hippocampus in human declarative learning has been challenged. Recently, we have shown that gains in performance observed in motor sequence learning (MSL) during the quiet rest periods interleaved with practice are associated with increased hippocampal activity, suggesting a role of this structure in motor memory reactivation. Yet, skill also develops offline as memory stabilizes after training and overnight. To examine whether the hippocampus contributes to motor sequence memory consolidation, here we used a network neuroscience strategy to track its functional connectivity offline 30min and 24h post learning using resting-state functional magnetic resonance imaging. Using a graph-analytical approach we found that MSL transiently increased network modularity, reflected in an increment in local information processing at 30min that returned to baseline at 24h. Within the same time window, MSL decreased the connectivity of a hippocampal-sensorimotor network, and increased the connectivity of a striatal-premotor network in an antagonistic manner. Finally, a supervised classification identified a low-dimensional pattern of hippocampal connectivity that discriminated between control and MSL data with high accuracy. The fact that changes in hippocampal connectivity were detected shortly after training supports a relevant role of the hippocampus in early stages of motor memory consolidation.

Network Neuroscience Untethered: Brain-Wide Immediate Early Gene Expression for the Analysis of Functional Connectivity in Freely Behaving Animals.

Studying how spatially discrete neuroanatomical regions across the brain interact is critical to advancing our understanding of the brain. Traditional neuroimaging techniques have led to many important discoveries about the nature of these interactions, termed functional connectivity. However, in animal models these traditional neuroimaging techniques have generally been limited to anesthetized or head-fixed setups or examination of small subsets of neuroanatomical regions. Using the brain-wide expression density of immediate early genes (IEG), we can assess brain-wide functional connectivity underlying a wide variety of behavioural tasks in freely behaving animal models. Here, we provide an overview of the necessary steps required to perform IEG-based analyses of functional connectivity. We also outline important considerations when designing such experiments and demonstrate the implications of these considerations using an IEG-based network dataset generated for the purpose of this review.

Investigating cognitive neuroscience theories of human intelligence: A connectome-based predictive modeling approach.

Central to modern neuroscientific theories of human intelligence is the notion that general intelligence depends on a primary brain region or network, engaging spatially localized (rather than global) neural representations. Recent findings in network neuroscience, however, challenge this assumption, providing evidence that general intelligence may depend on system-wide network mechanisms, suggesting that local representations are necessary but not sufficient to account for the neural architecture of human intelligence. Despite the importance of this key theoretical distinction, prior research has not systematically investigated the role of local versus global neural representations in predicting general intelligence. We conducted a large-scale connectome-based predictive modeling study (N= 297), administering resting-state fMRI and a comprehensive cognitive battery to evaluate the efficacy of modern neuroscientific theories of human intelligence, including spatially localized theories (Lateral Prefrontal Cortex Theory, Parieto-Frontal Integration Theory, and Multiple Demand Theory) and recent global accounts (Process Overlap Theory and Network Neuroscience Theory). The results of our study demonstrate that general intelligence can be predicted by local functional connectivity profiles but is most robustly explained by global profiles of whole-brain connectivity. Our findings further suggest that the improved efficacy of global theories is not reducible to a greater strength or number of connections, but instead results from considering both strong and weak connections that provide the basis for intelligence (as predicted by the Network Neuroscience Theory). Our results highlight the importance of considering local neural representations in the context of a global information-processing architecture, suggesting future directions for theory-driven research on system-wide network mechanisms underlying general intelligence.

Rethinking the neurosurgical approach to brain disorders from the network neuroscience perspective

Rethinking the neurosurgical approach to brain disorders from the network neuroscience perspective

Temporal Evolution of Multiday, Epileptic Functional Networks Prior to Seizure Occurrence.

Epilepsy is one of the most common neurological disorders, characterized by the occurrence of repeated seizures. Given that epilepsy is considered a network disorder, tools derived from network neuroscience may confer the valuable ability to quantify the properties of epileptic brain networks. In this study, we use well-established brain network metrics (i.e., mean strength, variance of strength, eigenvector centrality, betweenness centrality) to characterize the temporal evolution of epileptic functional networks over several days prior to seizure occurrence. We infer the networks using long-term electroencephalographic recordings from 12 people with epilepsy. We found that brain network metrics are variable across days and show a circadian periodicity. In addition, we found that in 9 out of 12 patients the distribution of the variance of strength in the day (or even two last days) prior to seizure occurrence is significantly different compared to the corresponding distributions on all previous days. Our results suggest that brain network metrics computed fromelectroencephalographic recordings could potentially be used to characterize brain network changes that occur prior to seizures, and ultimately contribute to seizure warning systems.

Bayesian network mediation analysis with application to the brain functional connectome.

The brain functional connectome, the collection of interconnected neural circuits along functional networks, facilitates a cutting-edge understanding of brain functioning, and has a potential to play a mediating role within the effect pathway between an exposure and an outcome. While existing mediation analytic approaches are capable of providing insight into complex processes, they mainly focus on a univariate mediator or mediator vector, without considering network-variate mediators. To fill the methodological gap and accomplish this exciting and urgent application, in the article, we propose an integrative mediation analysis under a Bayesian paradigm with networks entailing the mediation effect. To parameterize the network measurements, we introduce individually specified stochastic block models with unknown block allocation, and naturally bridge effect elements through the latent network mediators induced by the connectivity weights across network modules. To enable the identification of truly active mediating components, we simultaneously impose a feature selection across network mediators. We show the superiority of our model in estimating different effect components and selecting active mediating network structures. As a practical illustration of this approach's application to network neuroscience, we characterize the relationship between a therapeutic intervention and opioid abstinence as mediated by brain functional sub-networks.

Investigating cognitive ability using action-based models of structural brain networks

Abstract Recent developments in network neuroscience have highlighted the importance of developing techniques for analysing and modelling brain networks. A particularly powerful approach for studying complex neural systems is to formulate generative models that use wiring rules to synthesize networks closely resembling the topology of a given connectome. Successful models can highlight the principles by which a network is organized (identify structural features that arise from wiring rules versus those that emerge) and potentially uncover the mechanisms by which it grows and develops. Previous research has shown that such models can validate the effectiveness of spatial embedding and other (non-spatial) wiring rules in shaping the network topology of the human connectome. In this research, we propose variants of the action-based model that combine a variety of generative factors capable of explaining the topology of the human connectome. We test the descriptive validity of our models by evaluating their ability to explain between-subject variability. Our analysis provides evidence that geometric constraints are vital for connectivity between brain regions, and an action-based model relying on both topological and geometric properties can account for between-subject variability in structural network properties. Further, we test correlations between parameters of subject-optimized models and various measures of cognitive ability and find that higher cognitive ability is associated with an individual’s tendency to form long-range or non-local connections.

Abnormal Functional Hierarchies of EEG Networks in Familial and Sporadic Prodromal Alzheimer's Disease During Visual Short-Term Memory Binding.

Alzheimer's Disease (AD) shows both complex alterations of functional dependencies between brain regions and a decreased ability to perform Visual Short-Term Memory Binding (VSTMB) tasks. Recent advances in network neuroscience toward understanding the complexity of hierarchical brain function here enables us to establish a link between these two phenomena. Here, we study data on two types of dementia at Mild Cognitive Impairment (MCI) stage-familial AD patients (E280A mutation of the presenilin-1 gene) and elderly MCI patients at high risk of sporadic AD, both with age-matched controls. We analyzed Electroencephalogram (EEG) signals recorded during the performance of Visual Short-Term Memory (VSTM) tasks by these participants. Functional connectivity was computed using the phase-lag index in Alpha and Beta; and network analysis was employed using network indices of hierarchical spread (degree variance) and complexity. Hierarchical characteristics of EEG functional connectivity networks revealed abnormal patterns in familial MCI VSTMB function and sporadic MCI VSTMB function. The middle-aged familial MCI binding network displayed a larger degree variance in lower Beta compared to healthy controls (p = 0.0051, Cohen's d = 1.0124), while the elderly sporadic MCI binding network displayed greater hierarchical complexity in Alpha (p = 0.0140, Cohen's d = 1.1627). Characteristics in healthy aging were not shown to differ. These results indicate that activity in MCI exhibits cross-frequency network reorganization characterized by increased heterogeneity of node roles in the functional hierarchy. Aging itself is not found to cause VSTM functional hierarchy differences.

Self-organization of in vitro neuronal assemblies drives to complex network topology

Activity-dependent self-organization plays an important role in the formation of specific and stereotyped connectivity patterns in neural circuits. By combining neuronal cultures, and tools with approaches from network neuroscience and information theory, we can study how complex network topology emerges from local neuronal interactions. We constructed effective connectivity networks using a transfer entropy analysis of spike trains recorded from rat embryo dissociated hippocampal neuron cultures between 6 and 35 days in vitro to investigate how the topology evolves during maturation. The methodology for constructing the networks considered the synapse delay and addressed the influence of firing rate and population bursts as well as spurious effects on the inference of connections. We found that the number of links in the networks grew over the course of development, shifting from a segregated to a more integrated architecture. As part of this progression, three significant aspects of complex network topology emerged. In agreement with previous in silico and in vitro studies, a small-world architecture was detected, largely due to strong clustering among neurons. Additionally, the networks developed in a modular topology, with most modules comprising nearby neurons. Finally, highly active neurons acquired topological characteristics that made them important nodes to the network and integrators of modules. These findings leverage new insights into how neuronal effective network topology relates to neuronal assembly self-organization mechanisms.

Interacting brains revisited: A cross-brain network neuroscience perspective.

Elucidating the neural basis of social behavior is a long‐standing challenge in neuroscience. Such endeavors are driven by attempts to extend the isolated perspective on the human brain by considering interacting persons' brain activities, but a theoretical and computational framework for this purpose is still in its infancy. Here, we posit a comprehensive framework based on bipartite graphs for interbrain networks and address whether they provide meaningful insights into the neural underpinnings of social interactions. First, we show that the nodal density of such graphs exhibits nonrandom properties. While the current hyperscanning analyses mostly rely on global metrics, we encode the regions' roles via matrix decomposition to obtain an interpretable network representation yielding both global and local insights. With Bayesian modeling, we reveal how synchrony patterns seeded in specific brain regions contribute to global effects. Beyond inferential inquiries, we demonstrate that graph representations can be used to predict individual social characteristics, outperforming functional connectivity estimators for this purpose. In the future, this may provide a means of characterizing individual variations in social behavior or identifying biomarkers for social interaction and disorders.

The expanding horizons of network neuroscience: From description to prediction and control

The field of network neuroscience has emerged as a natural framework for the study of the brain and has been increasingly applied across divergent problems in neuroscience. From a disciplinary perspective, network neuroscience originally emerged as a formal integration of graph theory (from mathematics) and neuroscience (from biology). This early integration afforded marked utility in describing the interconnected nature of neural units, both structurally and functionally, and underscored the relevance of that interconnection for cognition and behavior. But since its inception, the field has not remained static in its methodological composition. Instead, it has grown to use increasingly advanced graph-theoretic tools and to bring in several other disciplinary perspectives—including machine learning and systems engineering—that have proven complementary. In doing so, the problem space amenable to the discipline has expanded markedly. In this review, we discuss three distinct flavors of investigation in state-of-the-art network neuroscience: (i) descriptive network neuroscience, (ii) predictive network neuroscience, and (iii) a perturbative network neuroscience that draws on recent advances in network control theory. In considering each area, we provide a brief summary of the approaches, discuss the nature of the insights obtained, and highlight future directions.

More than the sum of its parts: Merging network psychometrics and network neuroscience with application in autism

Network approaches that investigate the interaction between symptoms and behaviours have opened new ways of understanding psychological phenomena in health and disorder in recent years. In parallel, network approaches that characterise the interaction between brain regions have become the dominant approach in neuroimaging research. In this paper, we introduce a methodology for combining network psychometrics and network neuroscience. This approach utilises the information from the psychometric network to obtain neural correlates that are associated with each node in the psychometric network (network-based regression). Moreover, we combine the behavioural variables and their neural correlates in a joint network to characterise their interactions. We illustrate the approach by highlighting the interaction between the triad of autistic traits and their resting-state functional connectivity associations. To this end, we utilise data from 172 male autistic participants (10–21 years) from the autism brain data exchange (ABIDE, ABIDE-II) that completed resting-state fMRI and were assessed using the autism diagnostic interview (ADI-R). Our results indicate that the network-based regression approach can uncover both unique and shared neural correlates of behavioural measures. For instance, our example analysis indicates that the overlap between communication and social difficulties is not reflected in the overlap between their functional brain correlates.

Multimodal connectome biomarkers of cognitive and affective dysfunction in the common epilepsies.

Epilepsy is one of the most common chronic neurological conditions, traditionally defined as a disorder of recurrent seizures. Cognitive and affective dysfunction are increasingly recognized as core disease dimensions and can affect patient well-being, sometimes more than the seizures themselves. Connectome-based approaches hold immense promise for revealing mechanisms that contribute to dysfunction and to identify biomarkers. Our review discusses emerging multimodal neuroimaging and connectomics studies that highlight network substrates of cognitive/affective dysfunction in the common epilepsies. We first discuss work in drug-resistant epilepsy syndromes, that is, temporal lobe epilepsy, related to mesiotemporal sclerosis (TLE), and extratemporal epilepsy (ETE), related to malformations of cortical development. While these are traditionally conceptualized as ‘focal’ epilepsies, many patients present with broad structural and functional anomalies. Moreover, the extent of distributed changes contributes to difficulties in multiple cognitive domains as well as affective-behavioral challenges. We also review work in idiopathic generalized epilepsy (IGE), a subset of generalized epilepsy syndromes that involve subcortico-cortical circuits. Overall, neuroimaging and network neuroscience studies point to both shared and syndrome-specific connectome signatures of dysfunction across TLE, ETE, and IGE. Lastly, we point to current gaps in the literature and formulate recommendations for future research.

Null models in network neuroscience.

Recent advances in imaging and tracing technology provide increasingly detailed reconstructions of brain connectomes. Concomitant analytic advances enable rigorous identification and quantification of functionally important features of brain network architecture. Null models are a flexible tool to statistically benchmark the presence or magnitude of features of interest, by selectively preserving specific architectural properties of brain networks while systematically randomizing others. Here we describe the logic, implementation and interpretation of null models of connectomes. We introduce randomization and generative approaches to constructing null networks, and outline a taxonomy of network methods for statistical inference. We highlight the spectrum of null models - from liberal models that control few network properties, to conservative models that recapitulate multiple properties of empirical networks - that allow us to operationalize and test detailed hypotheses about the structure and function of brain networks. We review emerging scenarios for the application of null models in network neuroscience, including for spatially embedded networks, annotated networks and correlation-derived networks. Finally, we consider the limits of null models, as well as outstanding questions for the field.

Integrating Network Neuroscience Into Epilepsy Care: Progress, Barriers, and Next Steps.

Drug resistant epilepsy is a disorder involving widespread brain network alterations. Recently, many groups have reported neuroimaging and electrophysiology network analysis techniques to aid medical management, support presurgical planning, and understand postsurgical seizure persistence. While these approaches may supplement standard tests to improve care, they are not yet used clinically or influencing medical or surgical decisions. When will this change? Which approaches have shown the most promise? What are the barriers to translating them into clinical use? How do we facilitate this transition? In this review, we will discuss progress, barriers, and next steps regarding the integration of brain network analysis into the medical and presurgical pipeline.

Mechanisms for Cognitive Impairment in Epilepsy: Moving Beyond Seizures.

There has been a major emphasis on defining the role of seizures in the causation of cognitive impairments like memory deficits in epilepsy. Here we focus on an alternative hypothesis behind these deficits, emphasizing the mechanisms of information processing underlying healthy cognition characterized as rate, temporal and population coding. We discuss the role of the underlying etiology of epilepsy in altering neural networks thereby leading to both the propensity for seizures and the associated cognitive impairments. In addition, we address potential treatments that can recover the network function in the context of a diseased brain, thereby improving both seizure and cognitive outcomes simultaneously. This review shows the importance of moving beyond seizures and approaching the deficits from a system-level perspective with the guidance of network neuroscience.