Bridging Global and Local Topology in Whole-brain Networks using the Network Statistic Jackknife

2018 ◽  
Author(s):  
Teague R Henry ◽  
Kelly A. Duffy ◽  
Marc D. Rudolph ◽  
Mary Beth Nebel ◽  
Stewart H. Mostofsky ◽  
...  
Keyword(s):  
Network Analysis ◽  
Network Structure ◽  
Developmental Trajectories ◽  
R Package ◽  
Brain Network ◽  
Global Network ◽  
Group Differences ◽  
Network Organization ◽  
Whole Brain ◽  
Global Efficiency

Whole-brain network analysis is commonly used to investigate the topology of the brain in a variety of neuroimaging modalities. This approach is notable for its applicability to a large number of domains, such as understanding how brain network organization relates to cognition and behavior, examining disrupted brain network organization in disease, and assessing developmental trajectories across the lifespan. A benefit to this approach is the ability to summarize overall brain network organization with a single number (e.g., global efficiency). However, important local differences in network structure might exist without any corresponding observable differences in overall topology, making a whole-brain analysis strategy unlikely to detect relevant local findings. Here, we propose the network-based statistic (NBS) jackknife as a means of combining the utility of global network analysis strategies with the ability to detect relevant local differences in network structure. We describe the NBS jackknife framework, and demonstrate three specific testing scenarios in a series of examples. Finally, we provide an empirical example comparing global efficiency between children with ADHD and typically developing (TD) children. We demonstrate using functional connectivity data that there are no group differences in whole-brain global efficiency. Using the NBS jackknife, however, we identify group differences in global efficiency specific to the salience and subcortical subnetworks. The NBS jackknife framework has been implemented in a public, open source R package, netjack, available at https://cran.r-project.org/package=netjack.

scholarly journals Bridging global and local topology in whole-brain networks using the network statistic jackknife

2020 ◽  
Vol 4 (1) ◽  
pp. 70-88 ◽  
Author(s):  
Teague R. Henry ◽  
Kelly A. Duffy ◽  
Marc D. Rudolph ◽  
Mary Beth Nebel ◽  
Stewart H. Mostofsky ◽  
...  
Keyword(s):  
Network Analysis ◽  
Network Structure ◽  
R Package ◽  
Brain Network ◽  
Global Network ◽  
Local Network ◽  
Network Organization ◽  
Whole Brain ◽  
Global Efficiency ◽  
Global Topology

Whole-brain network analysis is commonly used to investigate the topology of the brain using a variety of neuroimaging modalities. This approach is notable for its applicability to a large number of domains, such as understanding how brain network organization relates to cognition and behavior and examining disrupted brain network organization in disease. A benefit to this approach is the ability to summarize overall brain network organization with a single metric (e.g., global efficiency). However, important local differences in network structure might exist without any corresponding observable differences in global topology, making a whole-brain analysis strategy unlikely to detect relevant local findings. Conversely, using local network metrics can identify local differences, but are not directly informative of differences in global topology. Here, we propose the network statistic (NS) jackknife framework, a simulated lesioning method that combines the utility of global network analysis strategies with the ability to detect relevant local differences in network structure. We evaluate the NS jackknife framework with a simulation study and an empirical example comparing global efficiency in children with attention-deficit/hyperactivity disorder (ADHD) and typically developing (TD) children. The NS jackknife framework has been implemented in a public, open-source R package, netjack, available at https://cran.r-project.org/package=netjack .

scholarly journals A whole-brain and cross-diagnostic perspective on functional brain network dysfunction

2018 ◽  
Author(s):  
Marjolein Spronk ◽  
Kaustubh Kulkarni ◽  
Jie Lisa Ji ◽  
Brian P. Keane ◽  
Alan Anticevic ◽  
...  
Keyword(s):  
Mental Illness ◽  
Resting State ◽  
Brain Network ◽  
Functional Network ◽  
Graph Distance ◽  
Network Organization ◽  
Whole Brain ◽  
Functional Brain ◽  
Functional Brain Network ◽  
Mental Diseases

AbstractA wide variety of mental disorders have been associated with resting-state functional network alterations, which are thought to contribute to the cognitive changes underlying mental illness. These observations have seemed to support various theories postulating large-scale disruptions of brain systems in mental illness. However, existing approaches isolate differences in network organization without putting those differences in broad, whole-brain perspective. Using a graph distance measure – connectome-wide correlation – we found that whole-brain resting-state functional network organization in humans is highly similar across a variety of mental diseases and healthy controls. This similarity was observed across autism spectrum disorder, attention-deficit hyperactivity disorder, and schizophrenia. Nonetheless, subtle differences in network graph distance were predictive of diagnosis, suggesting that while functional connectomes differ little across health and disease those differences are informative. Such small network alterations may reflect the fact that most psychiatric patients maintain overall cognitive abilities similar to those of healthy individuals (relative to, e.g., the most severe schizophrenia cases), such that whole-brain functional network organization is expected to differ only subtly even for mental diseases with devastating effects on everyday life. These results suggest a need to reevaluate neurocognitive theories of mental illness, with a role for subtle functional brain network changes in the production of an array of mental diseases.

scholarly journals Neurological Soft Signs and Brain Network Abnormalities in Schizophrenia

2019 ◽  
Vol 46 (3) ◽  
pp. 562-571 ◽  
Author(s):  
Li Kong ◽  
Christina J Herold ◽  
Eric F C Cheung ◽  
Raymond C K Chan ◽  
Johannes Schröder
Keyword(s):  
Network Analysis ◽  
Frontal Cortex ◽  
Temporal Cortex ◽  
Brain Network ◽  
Global Network ◽  
Orbital Frontal Cortex ◽  
Neural Basis ◽  
Neurological Soft Signs ◽  
Middle Temporal ◽  
Significant Difference

Abstract Neurological soft signs (NSS) are often found in patients with schizophrenia. A wealth of neuroimaging studies have reported that NSS are related to disturbed cortical-subcortical-cerebellar circuitry in schizophrenia. However, the association between NSS and brain network abnormalities in patients with schizophrenia remains unclear. In this study, the graph theoretical approach was used to analyze brain network characteristics based on structural magnetic resonance imaging (MRI) data. NSS were assessed using the Heidelberg scale. We found that there was no significant difference in global network properties between individuals with high and low levels of NSS. Regional network analysis showed that NSS were associated with betweenness centrality involving the inferior orbital frontal cortex, the middle temporal cortex, the hippocampus, the supramarginal cortex, the amygdala, and the cerebellum. Global network analysis also demonstrated that NSS were associated with the distribution of network hubs involving the superior medial frontal cortex, the superior and middle temporal cortices, the postcentral cortex, the amygdala, and the cerebellum. Our findings suggest that NSS are associated with alterations in topological attributes of brain networks corresponding to the cortical-subcortical-cerebellum circuit in patients with schizophrenia, which may provide a new perspective for elucidating the neural basis of NSS in schizophrenia.

scholarly journals Sensitivity and robustness of comorbidity network analysis

2019 ◽  
Author(s):  
Jason Cory Brunson ◽  
Thomas P. Agresta ◽  
Reinhard C. Laubenbacher
Keyword(s):  
Network Analysis ◽  
Network Structure ◽  
Global Network ◽  
Data Sets ◽  
Multivariate Models ◽  
Occurrence Data ◽  
Level Data ◽  
Pairwise Models ◽  
Global Statistics ◽  
Specific Symptoms

1Summary and KeywordsBackgroundComorbidity network analysis (CNA) is an increasingly popular approach in systems medicine, in which mathematical graphs encode epidemiological correlations (links) between diseases (nodes) inferred from their occurrence in an underlying patient population. A variety of methods have been used to infer properties of the constituent diseases or underlying populations from the network structure, but few have been validated or reproduced.ObjectivesTo test the robustness and sensitivity of several common CNA techniques to the source of population health data and the method of link determination.MethodsWe obtained six sources of aggregated disease co-occurrence data, coded using varied ontologies, most of which were provided by the authors of CNAs. We constructed families of comorbidity networks from these data sets, in which links were determined using a range of statistical thresholds and measures of association. We calculated degree distributions, single-value statistics, and centrality rankings for these networks and evaluated their sensitivity to the source of data and link determination parameters. From two open-access sources of patient-level data, we constructed comorbidity networks using several multivariate models in addition to comparable pairwise models and evaluated differences between correlation estimates and network structure.ResultsGlobal network statistics vary widely depending on the underlying population. Much of this variation is due to network density, which for our six data sets ranged over three orders of magnitude. The statistical threshold for link determination also had strong effects on global statistics, though at any fixed threshold the same patterns distinguished our six populations. The association measure used to quantify comorbid relations had smaller but discernible effects on global structure. Co-occurrence rates estimated using multivariate models were increasingly negative-shifted as models accounted for more effects. However, only associations between the most prevalent disorders were consistent from model to model. Centrality rankings were likewise similar when based on the same dataset using different constructions; but they were difficult to compare, and very different when comparable, between data sets, especially those using different ontologies. The most central disease codes were particular to the underlying populations and were often broad categories, injuries, or non-specific symptoms.ConclusionsCNAs can improve robustness and comparability by accounting for known limitations. In particular, we urge comorbidity network analysts (a) to include, where permissible, disaggregated disease occurrence data to allow more targeted reproduction and comparison of results; (b) to report differences in results obtained using different association measures, including both one of relative risk and one of correlation; (c) when identifying centrally located disorders, to carefully decide the most suitable ontology for this purpose; and, (d) when relevant to the interpretation of results, to compare them to those obtained using a multivariate model.

scholarly journals A Whole-Brain and Cross-Diagnostic Perspective on Functional Brain Network Dysfunction

2020 ◽  
Vol 31 (1) ◽  
pp. 547-561
Author(s):  
Marjolein Spronk ◽  
Brian P Keane ◽  
Takuya Ito ◽  
Kaustubh Kulkarni ◽  
Jie Lisa Ji ◽  
...  
Keyword(s):  
Mental Illness ◽  
Mental Disorders ◽  
Resting State ◽  
Brain Network ◽  
Graph Distance ◽  
Network Organization ◽  
Whole Brain ◽  
Functional Brain ◽  
Functional Brain Network ◽  
Mental Diseases

Abstract A wide variety of mental disorders have been associated with resting-state functional network alterations, which are thought to contribute to the cognitive changes underlying mental illness. These observations appear to support theories postulating large-scale disruptions of brain systems in mental illness. However, existing approaches isolate differences in network organization without putting those differences in a broad, whole-brain perspective. Using a graph distance approach—connectome-wide similarity—we found that whole-brain resting-state functional network organization is highly similar across groups of individuals with and without a variety of mental diseases. This similarity was observed across autism spectrum disorder, attention-deficit hyperactivity disorder, and schizophrenia. Nonetheless, subtle differences in network graph distance were predictive of diagnosis, suggesting that while functional connectomes differ little across health and disease, those differences are informative. These results suggest a need to reevaluate neurocognitive theories of mental illness, with a role for subtle functional brain network changes in the production of an array of mental diseases. Such small network alterations suggest the possibility that small, well-targeted alterations to brain network organization may provide meaningful improvements for a variety of mental disorders.

scholarly journals Muting, not fragmentation, of functional brain networks under general anesthesia

2020 ◽  
Author(s):  
Corson N. Areshenkoff ◽  
Joseph Y. Nashed ◽  
R. Matthew Hutchison ◽  
Melina Hutchison ◽  
Ron Levy ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Network Structure ◽  
Surrogate Data ◽  
Brain Network ◽  
Data Sets ◽  
Resting State Functional Connectivity ◽  
Whole Brain ◽  
Network Communities ◽  
Functional Brain Networks ◽  
Actual Change

AbstractChanges in resting-state functional connectivity (rs-FC) under general anesthesia have been widely studied with the goal of identifying neural signatures of consciousness. This work has commonly revealed an apparent fragmentation of whole-brain network structure during unconsciousness, which has been interpreted as reflecting a break-down in connectivity and disruption in the brains ability to integrate information. Here we show, by studying rs-FC under varying depths of isoflurane-induced anesthesia in nonhuman primates, that this apparent fragmentation, rather than reflecting an actual change in network structure, can be simply explained as the result of a global reduction in FC. Specifically, by comparing the actual FC data to surrogate data sets that we derived to test competing hypotheses of how FC changes as a function of dose, we found that increases in whole-brain modularity and the number of network communities considered hallmarks of fragmentation are artifacts of constructing FC networks by thresholding based on correlation magnitude. Taken together, our findings suggest that deepening levels of unconsciousness are instead associated with the increasingly muted expression of functional networks, an observation that constrains current interpretations as to how anesthesia-induced FC changes map onto existing neurobiological theories of consciousness.

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