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Brain network definitions typically assume nonoverlap or minimal overlap, ignoring regions' connections to multiple networks. However, new methods are emerging that emphasize network overlap. Here, we investigated the reliability and validity of one assignment method, the mixed membership algorithm, and explored its potential utility for identifying gaps in existing network models of cognition. We first assessed between-sample reliability of overlapping assignments with a split-half design; a bootstrapped Dice similarity analysis demonstrated good agreement between the networks from the two subgroups. Next, we assessed whether overlapping networks captured expected nonoverlapping topographies; overlapping networks captured portions of one to three nonoverlapping topographies, which aligned with canonical network definitions. Following this, a relative entropy analysis showed that a majority of regions participated in more than one network, as is seen biologically, and many regions did not show preferential connection to any one network. Finally, we explored overlapping network membership in regions of the dual-networks model of cognitive control, showing that almost every region was a member of multiple networks. Thus, the mixed membership algorithm produces consistent and biologically plausible networks, which presumably will allow for the development of more complete network models of cognition.

Many organizational principles of structural brain networks are established before birth and undergo considerable developmental changes afterwards. These include the topologically central hub regions and a densely connected rich club. While several studies have mapped developmental trajectories of brain connectivity and brain network organization across childhood and adolescence, comparatively little is known about subsequent development over the course of the lifespan. Here, we present a cross-sectional analysis of structural brain network development in N = 8,066 participants aged 5 to 80 years. Across all brain regions, structural connectivity strength followed an ‘inverted-U’-shaped trajectory with vertex in the early 30s. Connectivity strength of hub regions showed a similar trajectory and the identity of hub regions remained stable across all age groups. While connectivity strength declined with advancing age, the organization of hub regions into a rich club did not only remain intact but became more pronounced, presumingly through a selected sparing of relevant connections from age-related connectivity loss. The stability of rich club organization in the face of overall age-related decline is consistent with a “first come, last served” model of neurodevelopment, where the first principles to develop are the last to decline with age. Rich club organization has been shown to be highly beneficial for communicability and higher cognition. A resilient rich club might thus be protective of a functional loss in late adulthood and represent a neural reserve to sustain cognitive functioning in the aging brain.

Connectivity-based parcellation (CBP) methods are used to define homogenous and biologically meaningful parcels or nodes—the foundations of brain network fingerprinting—by grouping voxels with similar patterns of brain connectivity. However, we still lack a gold standard method and the use of CBPs to study the aging brain remains scarce. Our study proposes a novel CBP method from diffusion MRI data and shows its potential to produce a more accurate characterization of the longitudinal alterations in brain network topology occurring in aging. For this, we constructed whole-brain connectivity maps from diffusion MRI data of two datasets: an aging cohort evaluated at two timepoints (mean interval time: 52.8 ± 7.24 months) and a normative adult cohort—MGH-HCP. State-of-the-art clustering techniques were used to identify the best performing technique. Furthermore, we developed a new metric (connectivity homogeneity fingerprint [CHF]) to evaluate the success of the final CBP in improving regional/global structural connectivity homogeneity. Our results show that our method successfully generates highly homogeneous parcels, as described by the significantly larger CHF score of the resulting parcellation, when compared to the original. Additionally, we demonstrated that the developed parcellation provides a robust anatomical framework to assess longitudinal changes in the aging brain. Our results reveal that aging is characterized by a reorganization of the brain's structural network involving the decrease of intra-hemispheric, increase of inter-hemispheric connectivity, and topological rearrangement. Overall, this study proposes a new methodology to perform accurate and robust evaluations of CBP of the human brain.

The ability to regulate emotions is key to goal attainment and well-being. Although much has been discovered about neurodevelopment and the acquisition of emotion regulation, very little of this work has leveraged information encoded in whole-brain networks. Here we employed a network neuroscience framework to parse the neural underpinnings of emotion regulation skill acquisition, while accounting for age, in a sample of children and adolescents (N = 70, 34 female, aged 8–17 years). Focusing on three key network metrics—network differentiation, modularity, and community number differences between active regulation and a passive emotional baseline—we found that the control network, the default mode network, and limbic network were each related to emotion regulation ability while controlling for age. Greater network differentiation in the control and limbic networks was related to better emotion regulation ability. With regards to network community structure (modularity and community number), more communities and more crosstalk between modules (i.e., less modularity) in the control network were associated with better regulatory ability. By contrast, less crosstalk (i.e., greater modularity) between modules in the default mode network was associated with better regulatory ability. Together, these findings highlight whole-brain connectome features that support the acquisition of emotion regulation in youth.

OBJECTIVE: Despite the overall success of responsive neurostimulation (RNS) therapy for drug-resistant focal epilepsy, clinical outcomes in individuals vary significantly and are hard to predict. Biomarkers that indicate the clinical efficacy of RNS—ideally before device implantation—are critically needed, but challenges include the intrinsic heterogeneity of the RNS patient population and variability in clinical management across epilepsy centers. The aim of this study is to use a multicenter dataset to evaluate a candidate biomarker from intracranial electroencephalographic (iEEG) recordings that predicts clinical outcome with subsequent RNS therapy. METHODS: We assembled a federated dataset of iEEG recordings, collected prior to RNS implantation, from a retrospective cohort of 30 patients across three major epilepsy centers. Using ictal iEEG recordings, each center independently calculated network synchronizability, a candidate biomarker indicating the susceptibility of epileptic brain networks to RNS therapy. RESULTS: Ictal measures of synchronizability in the high-γ band (95–105 Hz) significantly distinguish between good and poor RNS responders after at least 3 years of therapy under the current RNS therapy guidelines (area under the curve = .83). Additionally, ictal high-γ synchronizability is inversely associated with the degree of therapeutic response. SIGNIFICANCE: This study provides a proof-of-concept roadmap for collaborative biomarker evaluation in federated data, where practical considerations impede full data sharing across centers. Our results suggest that network synchronizability can help predict therapeutic response to RNS therapy. With further validation, this biomarker could facilitate patient selection and help avert a costly, invasive intervention in patients who are unlikely to benefit.

The symptoms of acute ischemic stroke can be attributed to disruption of the brain network architecture. Systemic thrombolysis is an effective treatment that preserves structural connectivity in the first days after the event. Its effect on the evolution of global network organisation is, however, not well understood. We present a secondary analysis of 269 patients from the randomized WAKE-UP trial, comparing 127 imaging-selected patients treated with alteplase with 142 controls who received placebo. We used indirect network mapping to quantify the impact of ischemic lesions on structural brain network organisation in terms of both global parameters of segregation and integration, and local disruption of individual connections. Network damage was estimated before randomization and again 22 to 36 h after administration of either alteplase or placebo. Evolution of structural network organisation was characterised by a loss in integration and gain in segregation, and this trajectory was attenuated by the administration of alteplase. Preserved brain network organization was associated with excellent functional outcome. Furthermore, the protective effect of alteplase was spatio-topologically nonuniform, concentrating on a subnetwork of high centrality supported in the salvageable white matter surrounding the ischemic cores. This interplay between the location of the lesion, the pathophysiology of the ischemic penumbra, and the spatial embedding of the brain network explains the observed potential of thrombolysis to attenuate topological network damage early after stroke. Our findings might, in the future, lead to new brain network-informed imaging biomarkers and improved prognostication in ischemic stroke. ispartof: HUMAN BRAIN MAPPING vol:43 issue:16 pages:5053-5065 ispartof: location:United States status: published

The analysis of brain-imaging data requires complex and often non-linear transformations to support findings on brain function or pathologies. And yet, recent work has shown that variability in the choices that one makes when analyzing data can lead to quantitatively and qualitatively different results, endangering the trust in conclusions1–3. Even within a given method or analytical technique, numerical instabilities could compromise findings4–7. We instrumented a structural-connectome estimation pipeline with Monte Carlo Arithmetic8, 9, a technique to introduce random noise in floating-point computations, and evaluated the stability of the derived connectomes, their features10, 11, and the impact on a downstream analysis12, 13. The stability of results was found to be highly dependent upon which features of the connectomes were evaluated, and ranged from perfectly stable (i.e. no observed variability across executions) to highly unstable (i.e. the results contained no trustworthy significant information). While the extreme range and variability in results presented here could severely hamper our understanding of brain organization in brain-imaging studies, it also leads to an increase in the reliability of datasets. This paper highlights the potential of leveraging the induced variance in estimates of brain connectivity to reduce the bias in networks alongside increasing the robustness of their applications in the detection or classification of individual differences. This paper demonstrates that stability evaluations are necessary for understanding error and bias inherent to scientific computing, and that they should be a component of typical analytical workflows.

Purpose This longitudinal study aimed to disentangle the impact of chemotherapy on fatigue and hypothetically associated functional brain network alterations. Methods In total, 34 breast cancer patients treated with chemotherapy (BCC +), 32 patients not treated with chemotherapy (BCC −), and 35 non-cancer controls (NC) were included. Fatigue was assessed using the EORTC QLQ-C30 fatigue subscale at two time points: baseline (T1) and six months after completion of chemotherapy or matched intervals (T2). Participants also underwent resting-state functional magnetic resonance imaging (rsfMRI). An atlas spanning 90 cortical and subcortical brain regions was used to extract time series, after which Pearson correlation coefficients were calculated to construct a brain network per participant per timepoint. Network measures of local segregation and global integration were compared between groups and timepoints and correlated with fatigue. Results As expected, fatigue increased over time in the BCC + group (p = 0.025) leading to higher fatigue compared to NC at T2 (p = 0.023). Meanwhile, fatigue decreased from T1 to T2 in the BCC − group (p = 0.013). The BCC + group had significantly lower local efficiency than NC at T2 (p = 0.033), while a negative correlation was seen between fatigue and local efficiency across timepoints and all participants (T1 rho = − 0.274, p = 0.006; T2 rho = − 0.207, p = 0.039). Conclusion Although greater fatigue and lower local functional network segregation co-occur in breast cancer patients after chemotherapy, the relationship between the two generalized across participant subgroups, suggesting that local efficiency is a general neural correlate of fatigue.

Recent studies provide novel insights into the meso-scale organization of the brain, highlighting the co-occurrence of different structures: classic assortative (modular), disassortative, and core-periphery. However, the spectral properties of the brain meso-scale remain mostly unexplored. To fill this knowledge gap, we investigated how the meso-scale structure is organized across the frequency domain. We analyzed the resting state activity of healthy participants with source-localized high-density electroencephalography signals. Then, we inferred the community structure using weighted stochastic block-model (WSBM) to capture the landscape of meso-scale structures across the frequency domain. We found that different meso-scale modalities co-exist and are diversely organized over the frequency spectrum. Specifically, we found a core-periphery structure dominance, but we also highlighted a selective increase of disassortativity in the low frequency bands (

International audience; Understanding the dynamics of brain-scale functional networks at rest and during cognitive tasks is the subject of intense research efforts to unveil fundamental principles of brain functions. To estimate these large-scale brain networks, the emergent method called "electroencephalography (EEG) source connectivity" has generated increasing interest in the network neuroscience community, due to its ability to identify cortical brain networks with satisfactory spatio-temporal resolution, while reducing mixing and volume conduction effects. However, no consensus has been reached yet regarding a unified EEG source connectivity pipeline, and several methodological issues have to be carefully accounted to avoid pitfalls. Thus, a validation toolbox that provides flexible "ground truth" models is needed for an objective methods/parameters evaluation and, thereby an optimization of the EEG source connectivity pipeline. In this paper, we show how a recently developed large-scale model of brain-scale activity, named COALIA, can provide to some extent such ground truth by providing realistic simulations of source-level and scalp-level activity. Using a bottom-up approach, the model bridges cortical micro-circuitry and large-scale network dynamics. Here, we provide an example of the potential use of COALIA to analyze, in the context of epileptiform activity, the effect of three key factors involved in the "EEG source connectivity" pipeline: (i) EEG sensors density, (ii) algorithm used to solve the inverse problem, and (iii) functional connectivity measure. Results showed that a high electrode density (at least 64 channels) is required to accurately estimate cortical networks. Regarding the inverse solution/connectivity measure combination, the best performance at high electrode density was obtained using the weighted minimum norm estimate (wMNE) combined with the weighted phase lag index (wPLI). Although those results are specific to the considered aforementioned context (epileptiform activity), we believe that this model-based approach can be successfully applied to other experimental questions/contexts. We aim at presenting a proof-of-concept of the interest of COALIA in the network neuroscience field, and its potential use in optimizing the EEG source-space network estimation pipeline.

Significance Despite significant research, the biological mechanisms underlying schizophrenia are still unclear. We shed light on structural brain differences in psychosis using an approach called morphometric similarity mapping, which quantifies the structural similarity between brain regions. Morphometric similarity was globally reduced in psychosis patients in three independent datasets, implying that patients’ brain regions were more differentiated from each other and less interconnected. Similarity was especially decreased in frontal and temporal regions. This anatomical pattern was correlated with expression of genes enriched for nervous system development and synaptic signaling and genes previously associated with schizophrenia and antipsychotic treatments. Therefore, we begin to see how combining genomics and imaging can give a more integrative understanding of schizophrenia, which might inform future treatments., Schizophrenia has been conceived as a disorder of brain connectivity, but it is unclear how this network phenotype is related to the underlying genetics. We used morphometric similarity analysis of MRI data as a marker of interareal cortical connectivity in three prior case–control studies of psychosis: in total, n = 185 cases and n = 227 controls. Psychosis was associated with globally reduced morphometric similarity in all three studies. There was also a replicable pattern of case–control differences in regional morphometric similarity, which was significantly reduced in patients in frontal and temporal cortical areas but increased in parietal cortex. Using prior brain-wide gene expression data, we found that the cortical map of case–control differences in morphometric similarity was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms and pathways. In addition, genes that were normally overexpressed in cortical areas with reduced morphometric similarity were significantly up-regulated in three prior post mortem studies of schizophrenia. We propose that this combined analysis of neuroimaging and transcriptional data provides insight into how previously implicated genes and proteins as well as a number of unreported genes in their topological vicinity on the protein interaction network may drive structural brain network changes mediating the genetic risk of schizophrenia.

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.

Network neuroscience shed some light on the functional and structural modifications occurring to the brain associated with the phenomenology of schizophrenia. In particular, resting-state functional networks have helped our understanding of the illness by highlighting the global and local alterations within the cerebral organization. We investigated the robustness of the brain functional architecture in forty-four medicated schizophrenic patients and forty healthy comparators through an advanced network analysis of resting-state functional magnetic resonance imaging data. The networks in patients showed more resistance to disconnection than in healthy controls, with an evident discrepancy between the two groups in the node degree distribution computed along a percolation process. Despite a substantial similarity of the basal functional organization between the two groups, the expected hierarchy of healthy brains modular organization is crumbled in schizophrenia, showing a peculiar arrangement of the functional connections, characterized by several topologically equivalent backbones., Comment: 37 pages, 8 figures

Contains fulltext : 226126.pdf (Publisher’s version ) (Open Access) 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. 12 p.

Graphical abstract, Highlights • Structural disconnectomes can be modelled without diffusion using tractography atlases. • Atlas-based and DTI-derived disconnectome topological metrics correlate strongly. • MS patient disconnectomes relate to clinical scores., The translational potential of MR-based connectivity modelling is limited by the need for advanced diffusion imaging, which is not part of clinical protocols for many diseases. In addition, where diffusion data is available, brain connectivity analyses rely on tractography algorithms which imply two major limitations. First, tracking algorithms are known to be sensitive to the presence of white matter lesions and therefore leading to interpretation pitfalls and poor inter-subject comparability in clinical applications such as multiple sclerosis. Second, tractography quality is highly dependent on the acquisition parameters of diffusion sequences, leading to a trade-off between acquisition time and tractography precision. Here, we propose an atlas-based approach to study the interplay between structural disconnectivity and lesions without requiring individual diffusion imaging. In a multi-centric setting involving three distinct multiple sclerosis datasets (containing both 1.5 T and 3 T data), we compare our atlas-based structural disconnectome computation pipeline to disconnectomes extracted from individual tractography and explore its clinical utility for reducing the gap between radiological findings and clinical symptoms in multiple sclerosis. Results using topological graph properties showed that overall, our atlas-based disconnectomes were suitable approximations of individual disconnectomes from diffusion imaging. Small-worldness was found to decrease for larger total lesion volumes thereby suggesting a loss of efficiency in brain connectivity of MS patients. Finally, the global efficiency of the created brain graph, combined with total lesion volume, allowed to stratify patients into subgroups with different clinical scores in all three cohorts.

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

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.

BACKGROUND: Machine learning (ML) can distinguish cases with psychotic disorder from healthy controls based on magnetic resonance imaging (MRI) data, but it is not yet clear which MRI metrics are the most informative for case-control ML, or how ML algorithms relate to the underlying biology.METHODS: We analyzed multimodal MRI data from 2 independent case-control studies of psychotic disorders (cases, n = 65, 28; controls, n = 59, 80) and compared ML accuracy across 5 selected MRI metrics from 3 modalities. Cortical thickness, mean diffusivity, and fractional anisotropy were estimated at each of 308 cortical regions, as well as functional and structural connectivity between each pair of regions. Functional connectivity data were also used to classify nonpsychotic siblings of cases (n = 64) and to distinguish cases from controls in a third independent study (cases, n = 67; controls, n = 81).RESULTS: In both principal studies, the most informative metric was functional MRI connectivity: The areas under the receiver operating characteristic curve were 88% and 76%, respectively. The cortical map of diagnostic connectivity features (ML weights) was replicable between studies (r = .27, p < .001); correlated with replicable case-control differences in functional MRI degree centrality and with a prior cortical map of adolescent development of functional connectivity; predicted intermediate probabilities of psychosis in siblings; and was replicated in the third case-control study.CONCLUSIONS: ML most accurately distinguished cases from controls by a replicable pattern of functional MRI connectivity features, highlighting abnormal hubness of cortical nodes in an anatomical pattern consistent with the concept of psychosis as a disorder of network development.

Endel Tulving's proposal that episodic memory is distinct from other memory systems like semantic memory remains an extremely influential idea in cognitive neuroscience research. As originally suggested by Tulving, episodic memory involves three key components that differentiate it from all other memory systems: spatiotemporal binding, mental time travel, and autonoetic consciousness. Here, we focus on the idea of spatiotemporal binding in episodic memory and, in particular, how consideration of the precision of spatiotemporal context helps expand our understanding of episodic memory. Precision also helps shed light on another key issue in cognitive neuroscience, the role of the hippocampus outside of episodic memory in perception, attention, and working memory. By considering precision alongside item-context bindings, we attempt to shed new light on both the nature of how we represent context and what roles the hippocampus plays in episodic memory and beyond.

International audience; Objective: Motor imagery-based brain-computer interfaces (BCIs) use an individual's ability to volitionally modulate localized brain activity, often as a therapy for motor dysfunction or to probe causal relations between brain activity and behavior. However, many individuals cannot learn to successfully modulate their brain activity, greatly limiting the efficacy of BCI for therapy and for basic scientific inquiry. Formal experiments designed to probe the nature of BCI learning have offered initial evidence that coherent activity across spatially distributed and functionally diverse cognitive systems is a hallmark of individuals who can successfully learn to control the BCI. However, little is known about how these distributed networks interact through time to support learning.Approach: Here, we address this gap in knowledge by constructing and applying a multimodal network approach to decipher brain-behavior relations in motor imagery-based brain-computer interface learning using magnetoencephalography. Specifically, we employ a minimally constrained matrix decomposition method - non-negative matrix factorization - to simultaneously identify regularized, covarying subgraphs of functional connectivity, to assess their similarity to task performance, and to detect their time-varying expression.Main results: We find that learning is marked by diffuse brain-behavior relations: good learners displayed many subgraphs whose temporal expression tracked performance. Individuals also displayed marked variation in the spatial properties of subgraphs such as the connectivity between the frontal lobe and the rest of the brain, and in the temporal properties of subgraphs such as the stage of learning at which they reached maximum expression. From these observations, we posit a conceptual model in which certain subgraphs support learning by modulating brain activity in sensors near regions important for sustaining attention. To test this model, we use tools that stipulate regional dynamics on a networked system (network control theory), and find that good learners display a single subgraph whose temporal expression tracked performance and whose architecture supports easy modulation of sensors located near brain regions important for attention.Significance: The nature of our contribution to the neuroscience of BCI learning is therefore both computational and theoretical; we first use a minimally-constrained, individual specific method of identifying mesoscale structure in dynamic brain activity to show how global connectivity and interactions between distributed networks supports BCI learning, and then we use a formal network model of control to lend theoretical support to the hypothesis that these identified subgraphs are well suited to modulate attention.

Human brain mapping 41(10), 2553-2566 (2020). doi:10.1002/hbm.24982, Published by Wiley-Liss, New York, NY

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.

Patients with drug-resistant epilepsy often require surgery to become seizure-free. While laser ablation and implantable stimulation devices have lowered the morbidity of these procedures, seizure-free rates have not dramatically improved, particularly for patients without focal lesions. This is in part because it is often unclear where to intervene in these cases. To address this clinical need, several research groups have published methods to map epileptic networks but applying them to improve patient care remains a challenge. In this study we advance clinical translation of these methods by: (i) presenting and sharing a robust pipeline to rigorously quantify the boundaries of the resection zone and determining which intracranial EEG electrodes lie within it; (ii) validating a brain network model on a retrospective cohort of 28 patients with drug-resistant epilepsy implanted with intracranial electrodes prior to surgical resection; and (iii) sharing all neuroimaging, annotated electrophysiology, and clinical metadata to facilitate future collaboration. Our network methods accurately forecast whether patients are likely to benefit from surgical intervention based on synchronizability of intracranial EEG (area under the receiver operating characteristic curve of 0.89) and provide novel information that traditional electrographic features do not. We further report that removing synchronizing brain regions is associated with improved clinical outcome, and postulate that sparing desynchronizing regions may further be beneficial. Our findings suggest that data-driven network-based methods can identify patients likely to benefit from resective or ablative therapy, and perhaps prevent invasive interventions in those unlikely to do so.

Stress engendered by stereotype threatening situations may facilitate encoding of negative, stereotype confirming feedback received during a performance among women in science, technology, engineering and mathematics (STEM). It is unclear, however, whether this process is comprised of the same neurophysiological mechanisms evident in any emotional memory encoding context, or if this encoding bias directly undermines positive self-perceptions in the stigmatized domain. A total of 160 men and women completed a math test that provided veridical positive and negative feedback, a memory test for feedback, and math self-enhancing and valuing measures in a stereotype threatening or neutral context while continuous electroencephalography activity and startle probe responses to positive and negative feedback was recorded. Indexing amygdala activity to feedback via startle responses and emotional memory network connectivity elicited during accurate recognition of positive and negative feedback via graph analyses, only stereotype threatened women encoded negative feedback better when they exhibited increased amygdala activity and emotional memory network connectivity in response to said feedback. Emotional memory biases, in turn, predicted decreases in women’s self-enhancing, math valuing and performance. Findings provide an emotional memory encoding-based mechanism for well-established findings indicating that women have more negative math self-perceptions compared with men regardless of actual performance.

Encoding brain regions and their connections as a network of nodes and edges captures many of the possible paths along which information can be transmitted as humans process and perform complex behaviors. Because cognitive processes involve large, distributed networks of brain areas, principled examinations of multi-node routes within larger connection patterns can offer fundamental insights into the complexities of brain function. Here, we investigate both densely connected groups of nodes that could perform local computations as well as larger patterns of interactions that would allow for parallel processing. Finding such structures necessitates that we move from considering exclusively pairwise interactions to capturing higher order relations, concepts naturally expressed in the language of algebraic topology. These tools can be used to study mesoscale network structures that arise from the arrangement of densely connected substructures called cliques in otherwise sparsely connected brain networks. We detect cliques (all-to-all connected sets of brain regions) in the average structural connectomes of 8 healthy adults scanned in triplicate and discover the presence of more large cliques than expected in null networks constructed via wiring minimization, providing architecture through which brain network can perform rapid, local processing. We then locate topological cavities of different dimensions, around which information may flow in either diverging or converging patterns. These cavities exist consistently across subjects, differ from those observed in null model networks, and --- importantly --- link regions of early and late evolutionary origin in long loops, underscoring their unique role in controlling brain function. These results offer a first demonstration that techniques from algebraic topology offer a novel perspective on structural connectomics, highlighting loop-like paths as crucial features in the human brain's structural architecture.

Network science and engineering provide a flexible and generalizable tool set to describe and manipulate complex systems characterized by heterogeneous interaction patterns among component parts. While classically applied to social systems, these tools have recently proven to be particularly useful in the study of the brain. In this review, we describe the nascent use of these tools to understand human cognition, and we discuss their utility in informing the meaningful and predictable perturbation of cognition in combination with the emerging capabilities of neurofeedback. To blend these disparate strands of research, we build on emerging conceptualizations of how the brain functions (as a complex network) and how we can develop and target interventions or modulations (as a form of network control). We close with an outline of current frontiers that bridge neurofeedback, connectomics, and network control theory to better understand human cognition.

Connections in nervous systems are disproportionately concentrated on a small subset of neural elements that act as network hubs. Hubs have been found across different species and scales ranging from C. elegans to mouse, rat, cat, macaque, and human, suggesting a role for genetic influences. The recent availability of brain-wide gene expression atlases provides new opportunities for mapping the transcriptional correlates of large-scale network-level phenotypes. Here we review studies that use these atlases to investigate gene expression patterns associated with hub connectivity in neural networks and present evidence that some of these patterns are conserved across species and scales.

ObjectiveTemporal 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. The current work sought to identify multidimensional associations between cognitive performance and structural network topology in TLE.MethodsWe studied 34 drug-resistant TLE patients and 25 age- and sex-matched healthy controls. All 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 clustering to derive cognitive subtypes and associated patterns of macroscale connectome anomalies.ResultsBoth 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 better the cognitive performance than morphometric measures. Thus, connectome characteristics featured as important markers of network reorganization and loss of inter-regional connectivity.ConclusionsThe multivariate approach emphasized the close interplay between cognitive impairment 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

Brain activity can be modelled as a temporal network of interconnected regions. Recently, in network neuroscience, temporal network models have gained popularity and their network properties have been related to cognition and behaviour. Here we demonstrate that calculating nodal properties that are dependent on temporal community structure (such as participation coefficient) in time-varying contexts leads to misleading results due to fluctuations of the community structure over time. Further, we present a temporal extension to the participation coefficient measure (temporal participation coefficient) that circumnavigates this problem by considering all community partitions a node is assigned to through time. Initially, we demonstrate that when controlling for temporal communities, different nodes and time-points are identified as hubs when compared to current approaches. The proposed method allows us to track a node’s integration through time while adjusting for the possible changes in community structure of the overall network

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.HighlightsThe topography of Default Network cortical regions varies across individuals.A community detection algorithm, spectral partitioning, was applied to rs-fMRI data.The algorithm identified individualized Default Network regions in mPFC and PCC.Default Network topography varied across individuals in mPFC, moreso than in PCC.Overlap of task effects with DN regions should be assessed at the individual level.

Network neuroscience represents the brain as a collection of regions and inter‐regional connections. Given its ability to formalize systems‐level models, network neuroscience has generated unique explanations of neural function and behavior. The mechanistic status of these explanations and how they can contribute to and fit within the field of neuroscience as a whole has received careful treatment from philosophers. However, these philosophical contributions have not yet reached many neuroscientists. Here we complement formal philosophical efforts by providing an applied perspective from and for neuroscientists. We discuss the mechanistic status of the explanations offered by network neuroscience and how they contribute to, enhance, and interdigitate with other types of explanations in neuroscience. In doing so, we rely on philosophical work concerning the role of causality, scale, and mechanisms in scientific explanations. In particular, we make the distinction between an explanation and the evidence supporting that explanation, and we argue for a scale‐free nature of mechanistic explanations. In the course of these discussions, we hope to provide a useful applied framework in which network neuroscience explanations can be exercised across scales and combined with other fields of neuroscience to gain deeper insights into the brain and behavior., On the nature of explanations offered by network science: A perspective from and for practicing neuroscientists This paper focuses on the level of neural networks. It argues that tools and models in network science can successfully bridge explanations of neural and cognitive phenomena at multiple scales. On the basis of various examples, Bertolero and Bassett explain how network neuroscience can uncover aspects the neural mechanisms of cognitive phenomena.

It is nearly 20 years since the concept of a small-world network was first quantitatively defined, by a combination of high clustering and short path length; and about 10 years since this metric of complex network topology began to be widely applied to analysis of neuroimaging and other neuroscience data as part of the rapid growth of the new field of connectomics. Here we review briefly the foundational concepts of graph theoretical estimation and generation of small-world networks. We take stock of some of the key developments in the field in the past decade and we consider in some detail the implications of recent studies using high-resolution tract-tracing methods to map the anatomical networks of the macaque and the mouse. In doing so, we draw attention to the important methodological distinction between topological analysis of binary or unweighted graphs, which have provided a popular but simple approach to brain network analysis in the past, and the topology of weighted graphs, which retain more biologically relevant information and are more appropriate to the increasingly sophisticated data on brain connectivity emerging from contemporary tract-tracing and other imaging studies. We conclude by highlighting some possible future trends in the further development of weighted small-worldness as part of a deeper and broader understanding of the topology and the functional value of the strong and weak links between areas of mammalian cortex., 13 pages, 8 figures in The Neuroscientist, 2016

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.

Human brain networks based on neuroimaging data have already proven useful in characterizing both normal and abnormal brain structure and function. However, many brain disorders are neurodevelopmental in origin, highlighting the need to go beyond characterizing brain organization in terms of static networks. Here, we review the fast-growing literature shedding light on developmental changes in network phenotypes. We begin with an overview of recent large-scale efforts to map healthy brain development, and we describe the key role played by longitudinal data including repeated measurements over a long period of follow-up. We also discuss the subtle ways in which healthy brain network development can inform our understanding of disorders, including work bridging the gap between macroscopic neuroimaging results and the microscopic level. Finally, we turn to studies of three specific neurodevelopmental disorders that first manifest primarily in childhood and adolescence/early adulthood, namely psychotic disorders, attention-deficit/hyperactivity disorder, and autism spectrum disorder. In each case we discuss recent progress in understanding the atypical features of brain network development associated with the disorder, and we conclude the review with some suggestions for future directions.

Network analysis can provide insight into key organizational principles of brain structure and help identify structural changes associated with brain disease. Though static differences between diseased and healthy networks are well characterized, the study of network dynamics, or how brain networks change over time, is increasingly central to understanding ongoing brain changes throughout disease. Accordingly, we present a short review of network models of spread, network dynamics, and network degeneration. Borrowing from recent suggestions, we divide this review into two processes by which brain networks can change: dynamics on networks, which are functional and pathological consequences taking place atop a static structural brain network; and dynamics of networks, which constitutes a changing structural brain network. We focus on diffusion magnetic resonance imaging-based structural or anatomic connectivity graphs. We address psychiatric disorders like schizophrenia; developmental disorders like epilepsy; stroke; and Alzheimer's disease and other neurodegenerative diseases.

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., 12 pages, 3 figures, review article

It is nearly 20 years since the concept of a small-world network was first quantitatively defined, by a combination of high clustering and short path length; and about 10 years since this metric of complex network topology began to be widely applied to analysis of neuroimaging and other neuroscience data as part of the rapid growth of the new field of connectomics. Here, we review briefly the foundational concepts of graph theoretical estimation and generation of small-world networks. We take stock of some of the key developments in the field in the past decade and we consider in some detail the implications of recent studies using high-resolution tract-tracing methods to map the anatomical networks of the macaque and the mouse. In doing so, we draw attention to the important methodological distinction between topological analysis of binary or unweighted graphs, which have provided a popular but simple approach to brain network analysis in the past, and the topology of weighted graphs, which retain more biologically relevant information and are more appropriate to the increasingly sophisticated data on brain connectivity emerging from contemporary tract-tracing and other imaging studies. We conclude by highlighting some possible future trends in the further development of weighted small-worldness as part of a deeper and broader understanding of the topology and the functional value of the strong and weak links between areas of mammalian cortex.

Schizophrenia has been conceived as a disorder of brain connectivity, but it is unclear how this network phenotype is related to the underlying genetics. We used morphometric similarity analysis of MRI data as a marker of interareal cortical connectivity in three prior case-control studies of psychosis: in total, n = 185 cases and n = 227 controls. Psychosis was associated with globally reduced morphometric similarity in all three studies. There was also a replicable pattern of case-control differences in regional morphometric similarity, which was significantly reduced in patients in frontal and temporal cortical areas but increased in parietal cortex. Using prior brain-wide gene expression data, we found that the cortical map of case-control differences in morphometric similarity was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms and pathways. In addition, genes that were normally overexpressed in cortical areas with reduced morphometric similarity were significantly up-regulated in three prior post mortem studies of schizophrenia. We propose that this combined analysis of neuroimaging and transcriptional data provides insight into how previously implicated genes and proteins as well as a number of unreported genes in their topological vicinity on the protein interaction network may drive structural brain network changes mediating the genetic risk of schizophrenia.