Brain Subnetworks Research Articles

Response Hand and Motor Set Differentially Modulate the Connectivity of Brain Pathways During Simple Uni-manual Motor Behavior.

We investigated the flexible modulation of undirected functional connectivity (uFC) of brain pathways during simple uni-manual responding. Two questions were central to our interests: (1) does response hand (dominant vs. non-dominant) differentially modulate connectivity and (2) are these effects related to responding under varying motor sets. fMRI data were acquired in twenty right-handed volunteers who responded with their right (dominant) or left (non-dominant) hand (blocked across acquisitions). Within acquisitions, the task oscillated between periodic responses (promoting the emergence of motor sets) or randomly induced responses (disrupting the emergence of motor sets). Conjunction analyses revealed eight shared nodes across response hand and condition, time series from which were analyzed. For right hand responses connectivity of the M1 ←→ Thalamus and SMA ←→ Parietal pathways was more significantly modulated during periodic responding. By comparison, for left hand responses, connectivity between five network pairs (including M1 and SMA, insula, basal ganglia, premotor cortex, parietal cortex, thalamus) was more significantly modulated during random responding. uFC analyses were complemented by directed FC based on multivariate autoregressive models of times series from the nodes. These results were complementary and highlighted significant modulation of dFC for SMA → Thalamus, SMA → M1, basal ganglia → Insula and basal ganglia → Thalamus. The results demonstrate complex effects of motor organization and task demand and response hand on different connectivity classes of fMRI data. The brain's sub-networks are flexibly modulated by factors related to motor organization and/or task demand, and our results have implications for assessment of medical conditions associated with motor dysfunction.

Diminished neural network dynamics after moderate and severe traumatic brain injury.

Over the past decade there has been increasing enthusiasm in the cognitive neurosciences around using network science to understand the system-level changes associated with brain disorders. A growing literature has used whole-brain fMRI analysis to examine changes in the brain’s subnetworks following traumatic brain injury (TBI). Much of network modeling in this literature has focused on static network mapping, which provides a window into gross inter-nodal relationships, but is insensitive to more subtle fluctuations in network dynamics, which may be an important predictor of neural network plasticity. In this study, we examine the dynamic connectivity with focus on state-level connectivity (state) and evaluate the reliability of dynamic network states over the course of two runs of intermittent task and resting data. The goal was to examine the dynamic properties of neural networks engaged periodically with task stimulation in order to determine: 1) the reliability of inter-nodal and network-level characteristics over time and 2) the transitions between distinct network states after traumatic brain injury. To do so, we enrolled 23 individuals with moderate and severe TBI at least 1-year post injury and 19 age- and education-matched healthy adults using functional MRI methods, dynamic connectivity modeling, and graph theory. The results reveal several distinct network “states” that were reliably evident when comparing runs; the overall frequency of dynamic network states are highly reproducible (r-values>0.8) for both samples. Analysis of movement between states resulted in fewer state transitions in the TBI sample and, in a few cases, brain injury resulted in the appearance of states not exhibited by the healthy control (HC) sample. Overall, the findings presented here demonstrate the reliability of observable dynamic mental states during periods of on-task performance and support emerging evidence that brain injury may result in diminished network dynamics.

Brain network segregation and integration during an epoch-related working memory fMRI experiment

The characterization of brain subnetwork segregation and integration has previously focused on changes that are detectable at the level of entire sessions or epochs of imaging data. In this study, we applied time-varying functional connectivity analysis together with temporal network theory to calculate point-by-point estimates in subnetwork segregation and integration during an epoch-based (2-back, 0-back, baseline) working memory fMRI experiment as well as during resting-state. This approach allowed us to follow task-related changes in subnetwork segregation and integration at a high temporal resolution. At a global level, the cognitively more taxing 2-back epochs elicited an overall stronger response of integration between subnetworks compared to the 0-back epochs. Moreover, the visual, sensorimotor and fronto-parietal subnetworks displayed characteristic and distinct temporal profiles of segregation and integration during the 0- and 2-back epochs. During the interspersed epochs of baseline, several subnetworks, including the visual, fronto-parietal, cingulo-opercular and dorsal attention subnetworks showed pronounced increases in segregation. Using a drift diffusion model we show that the response time for the 2-back trials are correlated with integration for the fronto-parietal subnetwork and correlated with segregation for the visual subnetwork. Our results elucidate the fast-evolving events with regard to subnetwork integration and segregation that occur in an epoch-related task fMRI experiment. Our findings suggest that minute changes in subnetwork integration are of importance for task performance.

Altered brain networks in psychogenic erectile dysfunction: a resting-state fMRI study.

Various neuroimaging studies had identified changes of cerebral activity and structures during the processes of sexual arousal. The identified brain regions were also believed to regulate emotional and cognitive processes. Yet, little was known about the neural mechanisms underlying psychogenic erectile dysfunction. Moreover, brain mechanisms mediating the processing of sexual arousal by these psychological processes were unclear. To investigate this issue, graph theory was applied to evaluate the topological properties of functional brain networks among 24 psychogenic erectile dysfunction patients and 26 healthy controls. Abnormal metrics and correlations with clinical characteristics were further analyzed. Our results showed that psychogenic erectile dysfunction had higher small-worldness and more modules. Furthermore, psychogenic erectile dysfunction showed altered path length and strength of the right superior frontal gyrus (dorsolateral), superior parietal gyrus, parahippocampal gyrus and left temporal pole (superior temporal gyrus), post-central gyrus, mainly located in the cognitive control and emotional regulation subnetworks. And the altered parameters of the small-worldness and right parahippocampal gyrus were related to the clinical characteristics of psychogenic erectile dysfunction. Together, our results suggested that psychogenic erectile dysfunction was associated with disruptions in the topological structure of functional brain subnetworks underlying the cognitive and emotional processes.

Learning about learning: Mining human brain sub-network biomarkers from fMRI data.

Modeling the brain as a functional network can reveal the relationship between distributed neurophysiological processes and functional interactions between brain structures. Existing literature on functional brain networks focuses mainly on a battery of network properties in “resting state” employing, for example, modularity, clustering, or path length among regions. In contrast, we seek to uncover functionally connected subnetworks that predict or correlate with cohort differences and are conserved within the subjects within a cohort. We focus on differences in both the rate of learning as well as overall performance in a sensorimotor task across subjects and develop a principled approach for the discovery of discriminative subgraphs of functional connectivity based on imaging acquired during practice. We discover two statistically significant subgraph regions: one involving multiple regions in the visual cortex and another involving the parietal operculum and planum temporale. High functional coherence in the former characterizes sessions in which subjects take longer to perform the task, while high coherence in the latter is associated with high learning rate (performance improvement across trials). Our proposed methodology is general, in that it can be applied to other cognitive tasks, to study learning or to differentiate between healthy patients and patients with neurological disorders, by revealing the salient interactions among brain regions associated with the observed global state. The discovery of such significant discriminative subgraphs promises a better data-driven understanding of the dynamic brain processes associated with high-level cognitive functions.

Estimating directed brain-brain and brain-heart connectivity through globally conditioned Granger causality approaches.

While a large body of research has focused on the study of within-brain physiological networks (i.e. brain connectivity) as well as their disease-related aberration, few investigators have focused on estimating the directionality of these brain-brain interaction which, given the complexity of brain networks, should be properly conditioned in order to avoid the high number of false positives commonly encountered when using bivariate approaches to brain connectivity estimation. Additionally, the constituents of a number of brain subnetworks, and in particular of the central autonomic network (CAN), are still not completely determined. In this study we present and validate a global conditioning approach to reconstructing directed networks using complex synthetic networks of nonlinear oscillators. We then employ our framework, along with a probabilistic model for heartbeat generation, to characterize the directed functional connectome of the human brain and to establish which parts of this connectome effect the directed central modulation of peripheral autonomic cardiovascular control. We demonstrate the effectiveness of our conditioning approach and unveil a top-down directed influence of the default mode network on the salience network, which in turn is seen to be the strongest modulator of directed autonomic cardiovascular control.

Enhanced structural connectivity within a brain sub-network supporting working memory and engagement processes after cognitive training

The structural connectome provides relevant information about experience and training-related changes in the brain. Here, we used network-based statistics (NBS) and graph theoretical analyses to study structural changes in the brain as a function of cognitive training. Fifty-six young women were divided in two groups (experimental and control). We assessed their cognitive function before and after completing a working memory intervention using a comprehensive battery that included fluid and crystallized abilities, working memory and attention control, and we also obtained structural MRI images. We acquired and analyzed diffusion-weighted images to reconstruct the anatomical connectome and we computed standardized changes in connectivity as well as group differences across time using NBS. We also compared group differences relying on a variety of graph-theory indices (clustering, characteristic path length, global and local efficiency and strength) for the whole network as well as for the sub-network derived from NBS analyses. Finally, we calculated correlations between these graph indices and training performance as well as the behavioral changes in cognitive function. Our results revealed enhanced connectivity for the training group within one specific network comprised of nodes/regions supporting cognitive processes required by the training (working memory, interference resolution, inhibition, and task engagement). Significant group differences were also observed for strength and global efficiency indices in the sub-network detected by NBS. Therefore, the connectome approach is a valuable method for tracking the effects of cognitive training interventions across specific sub-networks. Moreover, this approach allowsfor the computation of graph theoretical network metricstoquantifythetopological architecture of the brain networkdetected. The observed structural brain changes support the behavioral results reported earlier (see Colom, Román, et al., 2013)

Correlation between graphs with an application to brain network analysis

The global functional brain network (graph) is more suitable for characterizing brain states than local analysis of the connectivity of brain regions. Therefore, graph-theoretic approaches are natural methods to use for studying the brain. However, conventional graph theoretical analyses are limited due to the lack of formal statistical methods of estimation and inference. For example, the concept of correlation between two vectors of graphs has not yet been defined. Thus, the introduction of a notion of correlation between graphs becomes necessary to better understand how brain sub-networks interact. To develop a framework to infer correlation between graphs, one may assume that they are generated by models and that the parameters of the models are the random variables. Then, it is possible to define that two graphs are independent when the random variables representing their parameters are independent. In the real world, however, the model is rarely known, and consequently, the parameters cannot be estimated. By analyzing the graph spectrum, it is shown that the spectral radius is highly associated with the parameters of the graph model. Based on this, a framework for correlation inference between graphs is constructed and the approach illustrated on functional magnetic resonance imaging data on 814 subjects comprising 529 controls and 285 individuals diagnosed with autism spectrum disorder (ASD). Results show that correlations between the default-mode and control, default-mode and somatomotor, and default-mode and visual sub-networks are higher in individuals with ASD than in the controls.

Dynamics of the Human Structural Connectome Underlying Working Memory Training.

This is the first study to explore training-induced changes in the structural connectome using a well-controlled design to examine cognitive training with up-to-date neuroimaging methods. We found changes in global integration based on white matter connectivity within a frontoparietal attention network following adaptive working memory training compared with a nonadaptive comparison group. Furthermore, the impact of different diffusion MR metrics and more specific markers of white matter on the graph theoretical findings was evaluated. An increase in network global efficiency following working memory training was best captured when connection strengths were weighted by MR relaxation rates (influenced by myelination). These results are important for the optimization of cognitive training programs for healthy individuals and people with brain disease.

Reorganization of functionally connected brain subnetworks in high-functioning autism.

Previous functional connectivity studies have found both hypo- and hyper-connectivity in brains of individuals having autism spectrum disorder (ASD). Here we studied abnormalities in functional brain subnetworks in high-functioning individuals with ASD during free viewing of a movie containing social cues and interactions. Twenty-six subjects (13 with ASD) watched a 68-min movie during functional magnetic resonance imaging. For each subject, we computed Pearson's correlation between haemodynamic time-courses of each pair of 6-mm isotropic voxels. From the whole-brain functional networks, we derived individual and group-level subnetworks using graph theory. Scaled inclusivity was then calculated between all subject pairs to estimate intersubject similarity of connectivity structure of each subnetwork. Additional 54 individuals (27 with ASD) from the ABIDE resting-state database were included to test the reproducibility of the results. Between-group differences were observed in the composition of default-mode and ventro-temporal-limbic (VTL) subnetworks. The VTL subnetwork included amygdala, striatum, thalamus, parahippocampal, fusiform, and inferior temporal gyri. Further, VTL subnetwork similarity between subject pairs correlated significantly with similarity of symptom gravity measured with autism quotient. This correlation was observed also within the controls, and in the reproducibility dataset with ADI-R and ADOS scores. Our results highlight how the reorganization of functional subnetworks in individuals with ASD clarifies the mixture of hypo- and hyper-connectivity findings. Importantly, only the functional organization of the VTL subnetwork emerges as a marker of inter-individual similarities that co-vary with behavioral measures across all participants. These findings suggest a pivotal role of ventro-temporal and limbic systems in autism.

Brain enhancement through cognitive training: a new insight from brain connectome.

Owing to the recent advances in neurotechnology and the progress in understanding of brain cognitive functions, improvements of cognitive performance or acceleration of learning process with brain enhancement systems is not out of our reach anymore, on the contrary, it is a tangible target of contemporary research. Although a variety of approaches have been proposed, we will mainly focus on cognitive training interventions, in which learners repeatedly perform cognitive tasks to improve their cognitive abilities. In this review article, we propose that the learning process during the cognitive training can be facilitated by an assistive system monitoring cognitive workloads using electroencephalography (EEG) biomarkers, and the brain connectome approach can provide additional valuable biomarkers for facilitating leaners’ learning processes. For the purpose, we will introduce studies on the cognitive training interventions, EEG biomarkers for cognitive workload, and human brain connectome. As cognitive overload and mental fatigue would reduce or even eliminate gains of cognitive training interventions, a real-time monitoring of cognitive workload can facilitate the learning process by flexibly adjusting difficulty levels of the training task. Moreover, cognitive training interventions should have effects on brain sub-networks, not on a single brain region, and graph theoretical network metrics quantifying topological architecture of the brain network can differentiate with respect to individual cognitive states as well as to different individuals’ cognitive abilities, suggesting that the connectome is a valuable approach for tracking the learning progress. Although only a few studies have exploited the connectome approach for studying alterations of the brain network induced by cognitive training interventions so far, we believe that it would be a useful technique for capturing improvements of cognitive functions.

Highly adaptive tests for group differences in brain functional connectivity

Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that “there is currently no unique solution, but a spectrum of related methods and analytical strategies” to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters.The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not only easy to use, but also high-powered robustly across various scenarios. The usage and advantages of these novel tests are demonstrated on an Alzheimer's disease dataset and simulated data.

Coupled Stable Overlapping Replicator Dynamics for Multimodal Brain Subnetwork Identification.

Combining imaging modalities to synthesize their inherent strengths provides a promising means for improving brain subnetwork identification. We propose a multimodal integration technique based on a sex-differentiated formulation of replicator dynamics for identifying subnetworks of brain regions that exhibit high inter-connectivity both functionally and structurally. Our method has a number of desired properties, namely, it can operate on weighted graphs derived from functional magnetic resonance imaging (tMRI) and diffusion MRI (dMRI) data, allows for subnetwork overlaps, has an intrinsic criterion for setting the number of subnetworks, and provides statistical control on false node inclusion in the identified subnetworks via the incorporation of stability selection. We thus refer to our technique as coupled stable overlapping replicator dynamics (CSORD). On synthetic data, We demonstrate that CSORD achieves significantly higher subnetwork identification accuracy than state-of-the-art techniques. On real. data from the Human Connectome Project (HCP), we show that CSORD attains improved test-retest reliability on multiple network measures and superior task classification accuracy.

Inferring Group-Wise Consistent Multimodal Brain Networks via Multi-View Spectral Clustering

Quantitative modeling and analysis of structural and functional brain networks based on diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) data have received extensive interest recently. However, the regularity of these structural and functional brain networks across multiple neuroimaging modalities and also across different individuals is largely unknown. This paper presents a novel approach to inferring group-wise consistent brain subnetworks from multimodal DTI/resting-state fMRI datasets via multi-view spectral clustering of cortical networks, which were constructed upon our recently developed and validated large-scale cortical landmarks-DICCCOL (dense individualized and common connectivity-based cortical landmarks). We applied the algorithms on DTI data of 100 healthy young females and 50 healthy young males, obtained consistent multimodal brain networks within and across multiple groups, and further examined the functional roles of these networks. Our experimental results demonstrated that the derived brain networks have substantially improved inter-modality and inter-subject consistency.

Measuring network's entropy in ADHD: A new approach to investigate neuropsychiatric disorders

The application of graph analysis methods to the topological organization of brain connectivity has been a useful tool in the characterization of brain related disorders. However, the availability of tools, which enable researchers to investigate functional brain networks, is still a major challenge. Most of the studies evaluating brain images are based on centrality and segregation measurements of complex networks. In this study, we applied the concept of graph spectral entropy (GSE) to quantify the complexity in the organization of brain networks. In addition, to enhance interpretability, we also combined graph spectral clustering to investigate the topological organization of sub-network's modules. We illustrate the usefulness of the proposed approach by comparing brain networks between attention deficit hyperactivity disorder (ADHD) patients and the brain networks of typical developing (TD) controls. The main findings highlighted that GSE involving sub-networks comprising the areas mostly bilateral pre and post central cortex, superior temporal gyrus, and inferior frontal gyri were statistically different (p-value=0.002) between ADHD patients and TD controls. In the same conditions, the other conventional graph descriptors (betweenness centrality, clustering coefficient, and shortest path length) commonly used to identify connectivity abnormalities did not show statistical significant difference. We conclude that analysis of topological organization of brain sub-networks based on GSE can identify networks between brain regions previously unobserved to be in association with ADHD.

Multisensory integration for timing engages different brain networks

How does the brain integrate information from different senses into a unitary percept? What factors influence such multisensory integration? Using a rhythmic behavioral paradigm and functional magnetic resonance imaging, we identified networks of brain regions for perceptions of physically synchronous and asynchronous auditory–visual events. Measures of behavioral performance revealed the existence of three distinct perceptual states. Perception of asynchrony activated a network of the primary sensory, prefrontal, and inferior parietal cortices, perception of synchrony disengaged the inferior parietal cortex and further recruited the superior colliculus, and when no clear percept was established, only the residual areas comprised of prefrontal and sensory areas were active. These results indicate that distinct percepts arise within specific brain sub-networks, the components of which are differentially engaged and disengaged depending on the timing of environmental signals.