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Communication protocols in the brain connectome describe how to transfer information from one region to another. Typically, these protocols hinge on either the spatial distances between brain regions or the intensity of their connections. Yet, none of them combine both factors to achieve optimal efficiency. Here, we introduce a continuous spectrum of decentralized routing strategies that integrates link weights and the spatial embedding of connectomes to route signal transmission. We implemented the protocols on connectomes from individuals in two cohorts and on group-representative connectomes designed to capture weighted connectivity properties. We identified an intermediate domain of routing strategies, a sweet spot, where navigation achieves maximum communication efficiency at low transmission cost. This phenomenon is robust and independent of the particular configuration of weights. Our findings suggest an interplay between the intensity of neural connections and their topology and geometry that amplifies communicability, where weights play the role of noise in a stochastic resonance phenomenon. Such enhancement may support more effective responses to external and internal stimuli, underscoring the intricate diversity of brain functions.

Brain activity flow models estimate the movement of task-evoked activity over brain connections to help explain network-generated task functionality. Activity flow models have been shown to accurately generate task-evoked brain activations across a wide variety of brain regions and task conditions. However, these models have had limited explanatory power, given known issues with causal interpretations of the standard functional connectivity measures used to parameterize activity flow models. We show here that functional/effective connectivity (FC) measures grounded in causal principles facilitate mechanistic interpretation of activity flow models. We progress from simple to complex FC measures, with each adding algorithmic details reflecting causal principles. This reflects many neuroscientists’ preference for reduced FC measure complexity (to minimize assumptions, minimize compute time, and fully comprehend and easily communicate methodological details), which potentially trades off with causal validity. We start with Pearson correlation (the current field standard) to remain maximally relevant to the field, estimating causal validity across a range of FC measures using simulations and empirical fMRI data. Finally, we apply causal-FC-based activity flow modeling to a dorsolateral prefrontal cortex region (DLPFC), demonstrating distributed causal network mechanisms contributing to its strong activation during a working memory task. Notably, this fully distributed model is able to account for DLPFC working memory effects traditionally thought to rely primarily on within-region (i.e., not distributed) recurrent processes. Together, these results reveal the promise of parameterizing activity flow models using causal FC methods to identify network mechanisms underlying cognitive computations in the human brain.

Graph-theoretic metrics derived from neuroimaging data have been heralded as powerful tools for uncovering neural mechanisms of psychological traits, psychiatric disorders, and neurodegenerative diseases. In N = 8,185 human structural connectomes from UK Biobank, we examined the extent to which 11 commonly-used global graph-theoretic metrics index distinct versus overlapping information with respect to interindividual differences in brain organization. Using unthresholded, FA-weighted networks we found that all metrics other than Participation Coefficient were highly intercorrelated, both with each other (mean |r| = 0.788) and with a topologically-naïve summary index of brain structure (mean edge weight; mean |r| = 0.873). In a series of sensitivity analyses, we found that overlap between metrics is influenced by the sparseness of the network and the magnitude of variation in edge weights. Simulation analyses representing a range of population network structures indicated that individual differences in global graph metrics may be intrinsically difficult to separate from mean edge weight. In particular, Closeness, Characteristic Path Length, Global Efficiency, Clustering Coefficient, and Small Worldness were nearly perfectly collinear with one another (mean |r| = 0.939) and with mean edge weight (mean |r| = 0.952) across all observed and simulated conditions. Global graph-theoretic measures are valuable for their ability to distill a high-dimensional system of neural connections into summary indices of brain organization, but they may be of more limited utility when the goal is to index separable components of interindividual variation in specific properties of the human structural connectome.

Generative models of the human connectome enable in silico generation of brain networks based on probabilistic wiring rules. These wiring rules are governed by a small number of parameters that are typically fitted to individual connectomes and quantify the extent to which geometry and topology shape the generative process. A significant shortcoming of generative modeling in large cohort studies is that parameter estimation is computationally burdensome, and the accuracy and reliability of current estimation methods remain untested. Here, we propose a fast, reliable, and accurate parameter estimation method for connectome generative models that is scalable to large sample sizes. Our method achieves improved estimation accuracy and reliability and reduces computational cost by orders of magnitude, compared to established methods. We demonstrate an inherent tradeoff between accuracy, reliability, and computational expense in parameter estimation and provide recommendations for leveraging this tradeoff. To enable power analyses in future studies, we empirically approximate the minimum sample size required to detect between-group differences in generative model parameters. While we focus on the classic two-parameter generative model based on connection length and the topological matching index, our method can be generalized to other growth-based generative models. Our work provides a statistical and practical guide to parameter estimation for connectome generative models.

Communication protocols in the brain connectome describe how to transfer information from one region to another. Typically, these protocols hinge on either the spatial distances between brain regions or the intensity of their connections. Yet, none of them combine both factors to achieve optimal efficiency. Here, we introduce a continuous spectrum of decentralized routing strategies that integrates link weights and the spatial embedding of connectomes to route signal transmission. We implemented the protocols on connectomes from individuals in two cohorts and on group-representative connectomes designed to capture weighted connectivity properties. We identified an intermediate domain of routing strategies, a sweet spot , where navigation achieves maximum communication efficiency at low transmission cost. This phenomenon is robust and independent of the particular configuration of weights. Our findings suggest an interplay between the intensity of neural connections and their topology and geometry that amplifies communicability, where weights play the role of noise in a stochastic resonance phenomenon. Such enhancement may support more effective responses to external and internal stimuli, underscoring the intricate diversity of brain functions. [Display omitted] • Geometry, topology, and weights in human connectomes determine communicability. • Decentralized high-weight short-distance routing results in optimal navigability. • Information transfer is maximal when weights and spatial distances are balanced. • Maximum navigability is robust to severe injury in brain regions. • Maximum navigability is independent of the particular configuration of weights. [ABSTRACT FROM AUTHOR]

Adult cortex is organized into distributed functional communities. Yet, little is known about community architecture of children’s brains. Here, we uncovered the community structure of cortex in childhood using fMRI data from 670 children aged 9–11 years (48% female, replication sample n=544, 56% female) from the Adolescent Brain and Cognitive Development study. We first applied a data-driven community detection approach to cluster cortical regions into communities, then employed a generative model-based approach called the weighted stochastic block model to further probe community interactions. Children showed similar community structure to adults, as defined by Yeo and colleagues in 2011, in early-developing sensory and motor communities, but differences emerged in transmodal areas. Children have more cortical territory in the limbic community, which is involved in emotion processing, than adults. Regions in association cortex interact more flexibly across communities, creating uncertainty for the model-based assignment algorithm, and perhaps reflecting cortical boundaries that are not yet solidified. Uncertainty was highest for cingulo-opercular areas involved in flexible deployment of cognitive control. Activation and deactivation patterns during a working memory task showed that both the data-driven approach and a set of adult communities statistically capture functional organization in middle childhood. Collectively, our findings suggest that community boundaries are not solidified by middle childhood.

Activity observed in biological neural networks is determined by anatomical connectivity between cortical areas. The monkey frontoparietal network facilitates cognitive functions, but the organization of its connectivity is unknown. Here, a new connectivity matrix is proposed which shows that the network utilizes a small-world architecture and the 3-node M9 motif. Its areas exhibit relatively homogeneous connectivity with no suggestion of the hubs seen in scale-free networks. Crucially, its M9 dynamical relay motif is optimally arranged for near-zero and non-zero phase synchrony to arise in support of cognition, serving as a candidate topological mechanism for previously reported findings. These results can serve as a benchmark to be used in the treatment of neurological disorders where the types of cognition the frontoparietal network supports are impaired.

Interest in understanding the organization of the brain has led to the application of graph theory methods across a wide array of functional connectivity studies. The fundamental basis of a graph is the node. Recent work has shown that functional nodes reconfigure with brain state. To date, all graph theory studies of functional connectivity in the brain have used fixed nodes. Here, using fixed-, group-, state-specific, and individualized- parcellations for defining nodes, we demonstrate that functional connectivity changes within the nodes significantly influence the findings at the network level. In some cases, state- or group-dependent changes of the sort typically reported do not persist, while in others, changes are only observed when node reconfigurations are considered. The findings suggest that graph theory investigations into connectivity contrasts between brain states and/or groups should consider the influence of voxel-level changes that lead to node reconfigurations; the fundamental building block of a graph.

The brain can be modelled as a network with nodes and edges derived from a range of imaging modalities: the nodes correspond to spatially distinct regions and the edges to the interactions between them. Whole-brain connectivity studies typically seek to determine how network properties change with a given categorical phenotype such as age-group, disease condition or mental state. To do so reliably, it is necessary to determine the features of the connectivity structure that are common across a group of brain scans. Given the complex interdependencies inherent in network data, this is not a straightforward task. Some studies construct a group-representative network (GRN), ignoring individual differences, while other studies analyse networks for each individual independently, ignoring information that is shared across individuals. We propose a Bayesian framework based on exponential random graph models (ERGM) extended to multiple networks to characterise the distribution of an entire population of networks. Using resting-state fMRI data from the Cam-CAN project, a study on healthy ageing, we demonstrate how our method can be used to characterise and compare the brain’s functional connectivity structure across a group of young individuals and a group of old individuals.

Objective: Temporal lobe epilepsy (TLE) is known to affect large-scale structural networks and cognitive function in multiple domains. The study of complex relations between structural network organization and cognition requires comprehensive analytical methods and a shift towards multivariate techniques. Here, we sought to identify multidimensional associations between cognitive performance and structural network topology in TLE. Methods: We studied 34 drug-resistant adult TLE patients and 24 age- and sex-matched healthy controls. Participants underwent a comprehensive neurocognitive battery and multimodal MRI, allowing for large-scale connectomics, and morphological evaluation of subcortical and neocortical regions. Using canonical correlation analysis, we identified a multivariate mode that links cognitive performance to a brain structural network. Our approach was complemented by bootstrap-based hierarchical clustering to derive cognitive subtypes and associated patterns of macroscale connectome anomalies. Results: Both methodologies provided converging evidence for a close coupling between cognitive impairments across multiple domains and large-scale structural network compromise. Cognitive classes presented with an increasing gradient of abnormalities (increasing cortical and subcortical atrophy and less efficient white matter connectome organization in patients with increasing degrees of cognitive impairments). Notably, network topology characterized cognitive performance better than morphometric measures did. Conclusions: Our multivariate approach emphasized a close coupling of cognitive dysfunction and large-scale network anomalies in TLE. Our findings contribute to understand the complexity of structural connectivity regulating the heterogeneous cognitive deficits found in epilepsy.

The brain is organized into networks that reorganize dynamically in response to cognitive demands and exogenous stimuli. In recent years, repetitive transcranial magnetic stimulation (rTMS) has gained increasing use as a noninvasive means to modulate cortical physiology, with effects both proximal to the stimulation site and in distal areas that are intrinsically connected to the proximal target. In light of these network-level neuromodulatory effects, there has been a rapid growth in studies attempting to leverage information about network connectivity to improve neuromodulatory control and intervention outcomes. However, the mechanisms-of-action of rTMS on network-level effects remain poorly understood and is based primarily on heuristics from proximal stimulation findings. To help bridge this gap, the current paper presents a systematic review of 33 rTMS studies with baseline and post-rTMS measures of fMRI resting-state functional connectivity (RSFC). Literature synthesis revealed variability across studies in stimulation parameters, studied populations, and connectivity analysis methodology. Despite this variability, it is observed that active rTMS induces significant changes on RSFC, but the prevalent low-frequency-inhibition/high-frequency-facilitation heuristic endorsed for proximal rTMS effects does not fully describe distal connectivity findings. This review also points towards other important considerations, including that the majority of rTMS-induced changes were found outside the stimulated functional network, suggesting that rTMS effects tend to spread across networks. Future studies may therefore wish to adopt conventions and systematic frameworks, such as the Yeo functional connectivity parcellation atlas adopted here, to better characterize network-level effect that contribute to the efficacy of these rapidly developing noninvasive interventions.

Functional connectivity – the co-activation of brain regions – forms the basis of the brain’s functional architecture. Often measured during resting-state (i.e., in a task-free setting), patterns of functional connectivity within and between brain networks change with age. These patterns are of interest to aging researchers because age differences in resting-state connectivity relate to older adults’ relative cognitive declines. Less is known about age differences in large-scale brain networks during directed tasks. Recent work in younger adults has shown that patterns of functional connectivity are highly correlated between rest and task states. Whether this finding extends to older adults remains largely unexplored. To this end, we assessed younger and older adults’ functional connectivity across the whole brain using fMRI while participants underwent resting-state or completed directed tasks (e.g., a reasoning judgement task). Resting-state and task functional connectivity were less strongly correlated in older as compared to younger adults. This age-dependent difference could be attributed to significantly lower consistency in network organization between rest and task states among older adults. Older adults had less distinct or segregated networks during resting-state. This more diffuse pattern of organization was exacerbated during directed tasks. Finally, the default mode network, often implicated in neurocognitive aging, contributed strongly to this pattern. These findings establish that age differences in functional connectivity are state-dependent, providing greater insight into the mechanisms by which aging may lead to cognitive declines.

Regions of human medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) are part of the default network (DN), and additionally are implicated in diverse cognitive functions ranging from autobiographical memory to subjective valuation. Our ability to interpret the apparent co-localization of task-related effects with DN-regions is constrained by a limited understanding of the individual-level heterogeneity in mPFC/PCC functional organization. Here we used cortical surface-based meta-analysis to identify a parcel in human PCC that was more strongly associated with the DN than with valuation effects. We then used resting-state fMRI data and a data-driven network analysis algorithm, spectral partitioning, to partition mPFC and PCC into “DN” and “non-DN” subdivisions in individual participants (n = 100 from the Human Connectome Project). The spectral partitioning algorithm identified individual-level cortical subdivisions that varied markedly across individuals, especially in mPFC, and were reliable across test/retest datasets. Our results point toward new strategies for assessing whether distinct cognitive functions engage common or distinct mPFC subregions at the individual level.

A recurrent theme of both cognitive and network neuroscience is that the brain has a consistent subnetwork structure that maps onto functional specialization for different cognitive tasks, such as vision, motor skills, and attention. Understanding how regions in these subnetworks relate is thus crucial to understanding the emergence of cognitive processes. However, the organizing principles that guide how regions within subnetworks communicate, and whether there is a common set of principles across subnetworks, remains unclear. This is partly due to available tools not being suited to precisely quantify the role that different organizational principles play in the organization of a subnetwork. Here, we apply a joint modeling technique – the correlation generalized exponential random graph model (cGERGM) – to more completely quantify subnetwork structure. The cGERGM models a correlation network, such as those given in functional connectivity, as a function of activation motifs – consistent patterns of coactivation (i.e., connectivity) between collections of nodes that describe how the regions within a network are organized (e.g., clustering) – and anatomical properties – relationships between the regions that are dictated by anatomy (e.g., Euclidean distance). By jointly modeling all features simultaneously, the cGERGM models the unique variance accounted for by each feature, as well as a point estimate and standard error for each, allowing for significance tests against a random graph and between graphs. Across eight functional subnetworks, we find remarkably consistent organizational properties guiding subnetwork architecture, suggesting a fundamental organizational basis for subnetwork communication. Specifically, all subnetworks displayed greater clustering than would be expected by chance, but lower preferential attachment (i.e., hub use). These findings suggest that human functional subnetworks follow a segregated highway structure, in which tightly clustered subcommunities develop their own channels of communication rather than relying on hubs. • cGERGM is a joint modeling framework for quantifying correlation networks. • We quantify the unique contribution of different features in network organization. • Across subnetworks, we find a consistent set of organizational principles. • These networks show greater clustering than expected by chance. • Networks show less preferential attachment (i.e., hub use) than expected by chance. [ABSTRACT FROM AUTHOR]

• Activity flow models provide insight into how neurocognitive effects are generated from brain network interactions. • Functional connectivity methods grounded in statistical causal principles facilitate mechanistic interpretations of task activity flow models. • Mechanistic activity flow models accurately predict task-evoked neural effects across a wide variety of brain regions and cognitive tasks. Brain activity flow models estimate the movement of task-evoked activity over brain connections to help explain network-generated task functionality. Activity flow models have been shown to accurately generate task-evoked brain activations across a wide variety of brain regions and task conditions. However, these models have had limited explanatory power, given known issues with causal interpretations of the standard functional connectivity measures used to parameterize activity flow models. We show here that functional/effective connectivity (FC) measures grounded in causal principles facilitate mechanistic interpretation of activity flow models. We progress from simple to complex FC measures, with each adding algorithmic details reflecting causal principles. This reflects many neuroscientists' preference for reduced FC measure complexity (to minimize assumptions, minimize compute time, and fully comprehend and easily communicate methodological details), which potentially trades off with causal validity. We start with Pearson correlation (the current field standard) to remain maximally relevant to the field, estimating causal validity across a range of FC measures using simulations and empirical fMRI data. Finally, we apply causal-FC-based activity flow modeling to a dorsolateral prefrontal cortex region (DLPFC), demonstrating distributed causal network mechanisms contributing to its strong activation during a working memory task. Notably, this fully distributed model is able to account for DLPFC working memory effects traditionally thought to rely primarily on within-region (i.e., not distributed) recurrent processes. Together, these results reveal the promise of parameterizing activity flow models using causal FC methods to identify network mechanisms underlying cognitive computations in the human brain. [ABSTRACT FROM AUTHOR]

The human brain is in constant flux, as distinct areas engage in transient communication to support basic behaviors as well as complex cognition. The collection of interactions between cortical and subcortical areas forms a functional brain network whose topology evolves with time. Despite the nontrivial dynamics that are germane to this networked system, experimental evidence demonstrates that functional interactions organize into putative brain systems that facilitate different facets of cognitive computation. We hypothesize that such dynamic functional networks are organized around a set of rules that constrain their spatial architecture – which brain regions may functionally interact – and their temporal architecture – how these interactions fluctuate over time. To objectively uncover these organizing principles, we apply an unsupervised machine learning approach called non-negative matrix factorization to time-evolving, resting state functional networks in 20 healthy subjects. This machine learning approach automatically groups temporally co-varying functional interactions into subgraphs that represent putative topological modes of dynamic functional architecture. We find that subgraphs are stratified based on both the underlying modular organization and the topographical distance of their strongest interactions: while many subgraphs are largely contained within modules, others span between modules and are expressed differently over time. The relationship between dynamic subgraphs and modular architecture is further highlighted by the ability of time-varying subgraph expression to explain inter-individual differences in module reorganization. Collectively, these results point to the critical role that subgraphs play in constraining the topography and topology of functional brain networks. More broadly, this machine learning approach opens a new door for understanding the architecture of dynamic functional networks during both task and rest states, and for probing alterations of that architecture in disease. [ABSTRACT FROM AUTHOR]

• Global network metrics are used to measure organizational properties of the brain. • Many metrics are highly correlated with each other and with topology-free metrics. • Network sparsity and variation in edge weights may yield greater independence between metrics. Graph-theoretic metrics derived from neuroimaging data have been heralded as powerful tools for uncovering neural mechanisms of psychological traits, psychiatric disorders, and neurodegenerative diseases. In N = 8,185 human structural connectomes from UK Biobank, we examined the extent to which 11 commonly-used global graph-theoretic metrics index distinct versus overlapping information with respect to interindividual differences in brain organization. Using unthresholded, FA-weighted networks we found that all metrics other than Participation Coefficient were highly intercorrelated, both with each other (mean | r| = 0.788) and with a topologically-naïve summary index of brain structure (mean edge weight; mean | r| = 0.873). In a series of sensitivity analyses, we found that overlap between metrics is influenced by the sparseness of the network and the magnitude of variation in edge weights. Simulation analyses representing a range of population network structures indicated that individual differences in global graph metrics may be intrinsically difficult to separate from mean edge weight. In particular, Closeness, Characteristic Path Length, Global Efficiency, Clustering Coefficient, and Small Worldness were nearly perfectly collinear with one another (mean | r| = 0.939) and with mean edge weight (mean | r| = 0.952) across all observed and simulated conditions. Global graph-theoretic measures are valuable for their ability to distill a high-dimensional system of neural connections into summary indices of brain organization, but they may be of more limited utility when the goal is to index separable components of interindividual variation in specific properties of the human structural connectome. [ABSTRACT FROM AUTHOR]

The network architecture of the human brain has become a feature of increasing interest to the neuroscientific community, largely because of its potential to illuminate human cognition, its variation over development and aging, and its alteration in disease or injury. Traditional tools and approaches to study this architecture have largely focused on single scales—of topology, time, and space. Expanding beyond this narrow view, we focus this review on pertinent questions and novel methodological advances for the multi-scale brain. We separate our exposition into content related to multi-scale topological structure, multi-scale temporal structure, and multi-scale spatial structure. In each case, we recount empirical evidence for such structures, survey network-based methodological approaches to reveal these structures, and outline current frontiers and open questions. Although predominantly peppered with examples from human neuroimaging, we hope that this account will offer an accessible guide to any neuroscientist aiming to measure, characterize, and understand the full richness of the brain's multiscale network structure—irrespective of species, imaging modality, or spatial resolution. [ABSTRACT FROM AUTHOR]

The complexity of neural dynamics stems in part from the complexity of the underlying anatomy. Yet how white matter structure constrains how the brain transitions from one cognitive state to another remains unknown. Here we address this question by drawing on recent advances in network control theory to model the underlying mechanisms of brain state transitions as elicited by the collective control of region sets. We find that previously identified attention and executive control systems are poised to affect a broad array of state transitions that cannot easily be classified by traditional engineering-based notions of control. 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 neurophysiological noise. These results offer fundamental insights into the mechanisms driving brain state transitions in healthy cognition and their alteration following injury. [ABSTRACT FROM AUTHOR]

• We evaluate three parameter estimation methods for connectome generative models. • The three methods show a tradeoff between accuracy, reliability, and computational expense. • We develop a new fast, accurate and reliable estimation method. • We report minimum sample sizes required to detect between-group differences in model parameters. Generative models of the human connectome enable in silico generation of brain networks based on probabilistic wiring rules. These wiring rules are governed by a small number of parameters that are typically fitted to individual connectomes and quantify the extent to which geometry and topology shape the generative process. A significant shortcoming of generative modeling in large cohort studies is that parameter estimation is computationally burdensome, and the accuracy and reliability of current estimation methods remain untested. Here, we propose a fast, reliable, and accurate parameter estimation method for connectome generative models that is scalable to large sample sizes. Our method achieves improved estimation accuracy and reliability and reduces computational cost by orders of magnitude, compared to established methods. We demonstrate an inherent tradeoff between accuracy, reliability, and computational expense in parameter estimation and provide recommendations for leveraging this tradeoff. To enable power analyses in future studies, we empirically approximate the minimum sample size required to detect between-group differences in generative model parameters. While we focus on the classic two-parameter generative model based on connection length and the topological matching index, our method can be generalized to other growth-based generative models. Our work provides a statistical and practical guide to parameter estimation for connectome generative models. [ABSTRACT FROM AUTHOR]

• Children show similar community structure to adults in sensory and motor communities. • Association areas are less reliably assigned and interact flexibly across communities. • Uncertainty is high in attention areas, suggestive of unsolidified boundaries. • Data-driven community assignments are highly stable in a replication sample. [Display omitted] Adult cortex is organized into distributed functional communities. Yet, little is known about community architecture of children's brains. Here, we uncovered the community structure of cortex in childhood using fMRI data from 670 children aged 9–11 years (48% female, replication sample n = 544 , 56% female) from the Adolescent Brain and Cognitive Development study. We first applied a data-driven community detection approach to cluster cortical regions into communities, then employed a generative model-based approach called the weighted stochastic block model to further probe community interactions. Children showed similar community structure to adults, as defined by Yeo and colleagues in 2011, in early-developing sensory and motor communities, but differences emerged in transmodal areas. Children have more cortical territory in the limbic community, which is involved in emotion processing, than adults. Regions in association cortex interact more flexibly across communities, creating uncertainty for the model-based assignment algorithm, and perhaps reflecting cortical boundaries that are not yet solidified. Uncertainty was highest for cingulo-opercular areas involved in flexible deployment of cognitive control. Activation and deactivation patterns during a working memory task showed that both the data-driven approach and a set of adult communities statistically capture functional organization in middle childhood. Collectively, our findings suggest that community boundaries are not solidified by middle childhood. [ABSTRACT FROM AUTHOR]

Activity observed in biological neural networks is determined by anatomical connectivity between cortical areas. The monkey frontoparietal network facilitates cognitive functions, but the organization of its connectivity is unknown. Here, a new connectivity matrix is proposed which shows that the network utilizes a small-world architecture and the 3-node M9 motif. Its areas exhibit relatively homogeneous connectivity with no suggestion of the hubs seen in scale-free networks. Crucially, its M9 dynamical relay motif is optimally arranged for near-zero and non-zero phase synchrony to arise in support of cognition, serving as a candidate topological mechanism for previously reported findings. These results can serve as a benchmark to be used in the treatment of neurological disorders where the types of cognition the frontoparietal network supports are impaired. [ABSTRACT FROM AUTHOR]

Interest in understanding the organization of the brain has led to the application of graph theory methods across a wide array of functional connectivity studies. The fundamental basis of a graph is the node. Recent work has shown that functional nodes reconfigure with brain state. To date, all graph theory studies of functional connectivity in the brain have used fixed nodes. Here, using fixed-, group-, state-specific, and individualized- parcellations for defining nodes, we demonstrate that functional connectivity changes within the nodes significantly influence the findings at the network level. In some cases, state- or group-dependent changes of the sort typically reported do not persist, while in others, changes are only observed when node reconfigurations are considered. The findings suggest that graph theory investigations into connectivity contrasts between brain states and/or groups should consider the influence of voxel-level changes that lead to node reconfigurations; the fundamental building block of a graph. [ABSTRACT FROM AUTHOR]

• Exponential random graph models (ERGMs) are a flexible class of network models. • We develop a novel ERGM-based Bayesian multilevel model for groups of brain networks. • Fitting networks simultaneously yields more precise estimates for model parameters. • Our method can also assess differences in network properties between multiple groups. • We demonstrate our method on resting-state fMRI data from Cam-CAN, an ageing study. The brain can be modelled as a network with nodes and edges derived from a range of imaging modalities: the nodes correspond to spatially distinct regions and the edges to the interactions between them. Whole-brain connectivity studies typically seek to determine how network properties change with a given categorical phenotype such as age-group, disease condition or mental state. To do so reliably, it is necessary to determine the features of the connectivity structure that are common across a group of brain scans. Given the complex interdependencies inherent in network data, this is not a straightforward task. Some studies construct a group-representative network (GRN), ignoring individual differences, while other studies analyse networks for each individual independently, ignoring information that is shared across individuals. We propose a Bayesian framework based on exponential random graph models (ERGM) extended to multiple networks to characterise the distribution of an entire population of networks. Using resting-state fMRI data from the Cam-CAN project, a study on healthy ageing, we demonstrate how our method can be used to characterise and compare the brain's functional connectivity structure across a group of young individuals and a group of old individuals. [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy (TLE) is known to affect large-scale structural networks and cognitive function in multiple domains. The study of complex relations between structural network organization and cognition requires comprehensive analytical methods and a shift towards multivariate techniques. Here, we sought to identify multidimensional associations between cognitive performance and structural network topology in TLE. We studied 34 drug-resistant adult TLE patients and 24 age- and sex-matched healthy controls. Participants underwent a comprehensive neurocognitive battery and multimodal MRI, allowing for large-scale connectomics, and morphological evaluation of subcortical and neocortical regions. Using canonical correlation analysis, we identified a multivariate mode that links cognitive performance to a brain structural network. Our approach was complemented by bootstrap-based hierarchical clustering to derive cognitive subtypes and associated patterns of macroscale connectome anomalies. Both methodologies provided converging evidence for a close coupling between cognitive impairments across multiple domains and large-scale structural network compromise. Cognitive classes presented with an increasing gradient of abnormalities (increasing cortical and subcortical atrophy and less efficient white matter connectome organization in patients with increasing degrees of cognitive impairments). Notably, network topology characterized cognitive performance better than morphometric measures did. Our multivariate approach emphasized a close coupling of cognitive dysfunction and large-scale network anomalies in TLE. Our findings contribute to understand the complexity of structural connectivity regulating the heterogeneous cognitive deficits found in epilepsy. Image 1 • Multivariate models emphasized the interplay between cognitive impairment and large-scale network reorganization in TLE. • Network topology better captured cognitive dysfunction than morphometric measures. • Findings suggest a spectrum of structural-functional anomalies. [ABSTRACT FROM AUTHOR]

The brain is organized into networks that reorganize dynamically in response to cognitive demands and exogenous stimuli. In recent years, repetitive transcranial magnetic stimulation (rTMS) has gained increasing use as a noninvasive means to modulate cortical physiology, with effects both proximal to the stimulation site and in distal areas that are intrinsically connected to the proximal target. In light of these network-level neuromodulatory effects, there has been a rapid growth in studies attempting to leverage information about network connectivity to improve neuromodulatory control and intervention outcomes. However, the mechanisms-of-action of rTMS on network-level effects remain poorly understood and is based primarily on heuristics from proximal stimulation findings. To help bridge this gap, the current paper presents a systematic review of 33 rTMS studies with baseline and post-rTMS measures of fMRI resting-state functional connectivity (RSFC). Literature synthesis revealed variability across studies in stimulation parameters, studied populations, and connectivity analysis methodology. Despite this variability, it is observed that active rTMS induces significant changes on RSFC, but the prevalent low-frequency-inhibition/high-frequency-facilitation heuristic endorsed for proximal rTMS effects does not fully describe distal connectivity findings. This review also points towards other important considerations, including that the majority of rTMS-induced changes were found outside the stimulated functional network, suggesting that rTMS effects tend to spread across networks. Future studies may therefore wish to adopt conventions and systematic frameworks, such as the Yeo functional connectivity parcellation atlas adopted here, to better characterize network-level effect that contribute to the efficacy of these rapidly developing noninvasive interventions. • The mechanisms-of-action of rTMS on brain networks remains poorly understood. • This systematic review investigates rTMS changes in fMRI functional connectivity. • There is evidence of network-level effects that transcend the stimulated network. • These network effects have a frequency profile distinct from typical proximal effects. [ABSTRACT FROM AUTHOR]

Functional connectivity – the co-activation of brain regions – forms the basis of the brain's functional architecture. Often measured during resting-state (i.e., in a task-free setting), patterns of functional connectivity within and between brain networks change with age. These patterns are of interest to aging researchers because age differences in resting-state connectivity relate to older adults' relative cognitive declines. Less is known about age differences in large-scale brain networks during directed tasks. Recent work in younger adults has shown that patterns of functional connectivity are highly correlated between rest and task states. Whether this finding extends to older adults remains largely unexplored. To this end, we assessed younger and older adults' functional connectivity across the whole brain using fMRI while participants underwent resting-state or completed directed tasks (e.g., a reasoning judgement task). Resting-state and task functional connectivity were less strongly correlated in older as compared to younger adults. This age-dependent difference could be attributed to significantly lower consistency in network organization between rest and task states among older adults. Older adults had less distinct or segregated networks during resting-state. This more diffuse pattern of organization was exacerbated during directed tasks. Finally, the default mode network, often implicated in neurocognitive aging, contributed strongly to this pattern. These findings establish that age differences in functional connectivity are state-dependent, providing greater insight into the mechanisms by which aging may lead to cognitive declines. • Functional connectivity during rest and task states was highly correlated. • The rest-task correlation was lower in older versus younger adults. • Older adults also had lower consistency in network organization between states. • The default mode network strongly contributed to this pattern. [ABSTRACT FROM AUTHOR]

Regions of human medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) are part of the default network (DN), and additionally are implicated in diverse cognitive functions ranging from autobiographical memory to subjective valuation. Our ability to interpret the apparent co-localization of task-related effects with DN-regions is constrained by a limited understanding of the individual-level heterogeneity in mPFC/PCC functional organization. Here we used cortical surface-based meta-analysis to identify a parcel in human PCC that was more strongly associated with the DN than with valuation effects. We then used resting-state fMRI data and a data-driven network analysis algorithm, spectral partitioning, to partition mPFC and PCC into "DN" and "non-DN" subdivisions in individual participants (n = 100 from the Human Connectome Project). The spectral partitioning algorithm identified individual-level cortical subdivisions that varied markedly across individuals, especially in mPFC, and were reliable across test/retest datasets. Our results point toward new strategies for assessing whether distinct cognitive functions engage common or distinct mPFC subregions at the individual level. Image 1 • The topography of Default Network cortical regions varies across individuals. • A community detection algorithm, spectral partitioning, was applied to BOLD data. • The algorithm identified individualized Default Network regions in mPFC and PCC. • Default Network topography was more variable in mPFC than in PCC. • Overlap of task effects with DN regions should be assessed at the individual level. [ABSTRACT FROM AUTHOR]