Network Connectivity Patterns Research Articles

Resting-State Network Topology Differentiates Task Signals across the Adult Life Span.

Brain network connectivity differs across individuals. For example, older adults exhibit less segregated resting-state subnetworks relative to younger adults (Chan et al., 2014). It has been hypothesized that individual differences in network connectivity impact the recruitment of brain areas during task execution. While recent studies have described the spatial overlap between resting-state functional correlation (RSFC) subnetworks and task-evoked activity, it is unclear whether individual variations in the connectivity pattern of a brain area (topology) relates to its activity during task execution. We report data from 238 cognitively normal participants (humans), sampled across the adult life span (20–89 years), to reveal that RSFC-based network organization systematically relates to the recruitment of brain areas across two functionally distinct tasks (visual and semantic). The functional activity of brain areas (network nodes) were characterized according to their patterns of RSFC: nodes with relatively greater connections to nodes in their own functional system (“non-connector” nodes) exhibited greater activity than nodes with relatively greater connections to nodes in other systems (“connector” nodes). This “activation selectivity” was specific to those brain systems that were central to each of the tasks. Increasing age was accompanied by less differentiated network topology and a corresponding reduction in activation selectivity (or differentiation) across relevant network nodes. The results provide evidence that connectional topology of brain areas quantified at rest relates to the functional activity of those areas during task. Based on these findings, we propose a novel network-based theory for previous reports of the “dedifferentiation” in brain activity observed in aging.SIGNIFICANCE STATEMENT Similar to other real-world networks, the organization of brain networks impacts their function. As brain network connectivity patterns differ across individuals, we hypothesized that individual differences in network connectivity would relate to differences in brain activity. Using functional MRI in a group of individuals sampled across the adult life span (20–89 years), we measured correlations at rest and related the functional connectivity patterns to measurements of functional activity during two independent tasks. Brain activity varied in relation to connectivity patterns revealed by large-scale network analysis. This relationship tracked the differences in connectivity patterns accompanied by older age, providing important evidence for a link between the topology of areal connectivity measured at rest and the functional recruitment of these areas during task performance.

Network Connectivity of the Right STS in Three Social Perception Localizers.

The posterior STS (pSTS) is an important brain region for perceptual analysis of social cognitive cues. This study seeks to characterize the pattern of network connectivity emerging from the pSTS in three core social perception localizers: biological motion perception, gaze recognition, and the interpretation of moving geometric shapes as animate. We identified brain regions associated with all three of these localizers and computed the functional connectivity pattern between them and the pSTS using a partial correlations metric that characterizes network connectivity. We find a core pattern of cortical connectivity that supports the hypothesis that the pSTS serves as a hub of the social brain network. The right pSTS was the most highly connected of the brain regions measured, with many long-range connections to pFC. Unlike other highly connected regions, connectivity to the pSTS was distinctly lateralized. We conclude that the functional importance of right pSTS is revealed when considering its role in the large-scale network of brain regions involved in various aspects of social cognition.

Dendritic and Axonal Propagation Delays Determine Emergent Structures of Neuronal Networks with Plastic Synapses

Spike-timing-dependent plasticity (STDP) modifies synaptic strengths based on the relative timing of pre- and postsynaptic spikes. The temporal order of spikes turned out to be crucial. We here take into account how propagation delays, composed of dendritic and axonal delay times, may affect the temporal order of spikes. In a minimal setting, characterized by neglecting dendritic and axonal propagation delays, STDP eliminates bidirectional connections between two coupled neurons and turns them into unidirectional connections. In this paper, however, we show that depending on the dendritic and axonal propagation delays, the temporal order of spikes at the synapses can be different from those in the cell bodies and, consequently, qualitatively different connectivity patterns emerge. In particular, we show that for a system of two coupled oscillatory neurons, bidirectional synapses can be preserved and potentiated. Intriguingly, this finding also translates to large networks of type-II phase oscillators and, hence, crucially impacts on the overall hierarchical connectivity patterns of oscillatory neuronal networks.

Intelligent algorithms for improving communication patterns in thematic P2P search

The Internet is a cooperative and decentralized network built out of millions of participants that store and share large amounts of information with other users. Peer-to-peer systems go hand-in-hand with this huge decentralized network, where each individual node can serve content as well as request it. In this scenario, the analysis, development and testing of distributed search algorithms is a key research avenue. In particular, thematic search algorithms should lead to and benefit from the emergence of semantic communities that are the result of the interaction among participants. As a result, intelligent algorithms for neighbor selection should give rise to a logical network topology reflecting efficient communication patterns. This paper presents a series of algorithms which are specifically aimed at reducing the propagation of queries in the network, by applying a novel approach for learning peers’ interests. These algorithms were constructed in an incremental way so that each new algorithm presents some improvements over the previous ones. Several simulations were completed to analyze the connectivity and query propagation patterns of the emergent logical networks. The results indicate that the algorithms with better behavior are those that induce greater collaboration among peers.

Noninvasive Electromagnetic Source Imaging and Granger Causality Analysis: An Electrophysiological Connectome (eConnectome) Approach.

Combined source-imaging techniques and directional connectivity analysis can provide useful information about the underlying brain networks in a noninvasive fashion. Source-imaging techniques have been used successfully to either determine the source of activity or to extract source time-courses for Granger causality analysis, previously. In this work, we utilize source-imaging algorithms to both find the network nodes [regions of interest (ROI)] and then extract the activation time series for further Granger causality analysis. The aim of this work is to find network nodes objectively from noninvasive electromagnetic signals, extract activation time-courses, and apply Granger analysis on the extracted series to study brain networks under realistic conditions. Source-imaging methods are used to identify network nodes and extract time-courses and then Granger causality analysis is applied to delineate the directional functional connectivity of underlying brain networks. Computer simulations studies where the underlying network (nodes and connectivity pattern) is known were performed; additionally, this approach has been evaluated in partial epilepsy patients to study epilepsy networks from interictal and ictal signals recorded by EEG and/or Magnetoencephalography (MEG). Localization errors of network nodes are less than 5 mm and normalized connectivity errors of ∼20% in estimating underlying brain networks in simulation studies. Additionally, two focal epilepsy patients were studied and the identified nodes driving the epileptic network were concordant with clinical findings from intracranial recordings or surgical resection. Our study indicates that combined source-imaging algorithms with Granger causality analysis can identify underlying networks precisely (both in terms of network nodes location and internodal connectivity). The combined source imaging and Granger analysis technique is an effective tool for studying normal or pathological brain conditions.

Investigating Link Inference in Partially Observable Networks: Friendship Ties and Interaction

While privacy preserving mechanisms, such as hiding one’s friends list, may be available to withhold personal information on online social networking sites, it is not obvious whether to which degree a user’s social behavior renders such an attempt futile. In this paper, we study the impact of additional interaction information on the inference of links between nodes in partially covert networks. This investigation is based on the assumption that interaction might be a proxy for connectivity patterns in online social networks. For this purpose, we use data collected from 586 Facebook profiles consisting of friendship ties (conceptualized as the network) and comments on wall posts (serving as interaction information) by a total of 64 000 users. The link-inference problem is formulated as a binary classification problem using a comprehensive set of features and multiple supervised learning algorithms. Our results suggest that interactions reiterate the information contained in friendship ties sufficiently well to serve as a proxy when the majority of a network is unobserved.

Cross-Frequency rs-fMRI Network Connectivity Patterns Manifest Differently for Schizophrenia Patients and Healthy Controls.

Patterns of resting state fMRI functional network connectivity in schizophrenia patients have been shown to differ markedly from that of healthy controls. While some studies have explored connectivity within fixed frequency bands, the question of network phase synchrony across disparate frequency bands, or cross-frequency connectivity, has remained surprisingly underexplored. Computational modeling at the neuronal scale however has long acknowledged the existence of coupled fast and slow subsystems. Here we present preliminary evidence that cross-frequency coupling exists at the network level, that it patterns in meaningful ways over functional domains, and that this patterning differs between the healthy population and individuals with diagnosed schizophrenia.

Intrinsic network connectivity and own body perception in gender dysphoria.

Gender dysphoria (GD) is characterized by incongruence between one's identity and gender assigned at birth. The biological mechanisms of GD are unclear. We investigated brain network connectivity patterns involved in own body perception in the context of self in GD. Twenty-seven female-to-male (FtM) individuals with GD, 27 male controls, and 27 female controls underwent resting state fMRI. We compared functional connections within intrinsic connectivity networks involved in self-referential processes and own body perception -default mode network (DMN) and salience network - and visual networks, using independent components analyses. Behavioral correlates of network connectivity were also tested using self-perception ratings while viewing own body images morphed to their sex assigned at birth, and to the sex of their gender identity. FtM exhibited decreased connectivity of anterior and posterior cingulate and precuneus within the DMN compared with controls. In FtM, higher "self" ratings for bodies morphed towards the sex of their gender identity were associated with greater connectivity of the anterior cingulate within the DMN, during long viewing times. In controls, higher ratings for bodies morphed towards their gender assigned at birth were associated with right insula connectivity within the salience network, during short viewing times. Within visual networks FtM showed weaker connectivity in occipital and temporal regions. Results suggest disconnectivity within networks involved in own body perception in the context of self in GD. Moreover, perception of bodies in relation to self may be reflective rather than reflexive, as a function of mesial prefrontal processes. These may represent neurobiological correlates to the subjective disconnection between perception of body and self-identification.

Integrated Information and State Differentiation.

Integrated information (Φ) is a measure of the cause-effect power of a physical system. This paper investigates the relationship between Φ as defined in Integrated Information Theory and state differentiation (), the number of, and difference between potential system states. Here we provide theoretical justification of the relationship between Φ and , then validate the results using a simulation study. First, we show that a physical system in a state with high Φ necessarily has many elements and specifies many causal relationships. Furthermore, if the average value of integrated information across all states is high, the system must also have high differentiation. Next, we explore the use of as a proxy for Φ using artificial networks, evolved to have integrated structures. The results show a positive linear relationship between Φ and for multiple network sizes and connectivity patterns. Finally we investigate the differentiation evoked by sensory inputs and show that, under certain conditions, it is possible to estimate integrated information without a direct perturbation of its internal elements. In concluding, we discuss the need for further validation on larger networks and explore the potential applications of this work to the empirical study of consciousness, especially concerning the practical estimation of Φ from neuroimaging data.

Characterization of the Statistical Signatures of Micro-Movements Underlying Natural Gait Patterns in Children with Phelan McDermid Syndrome: Towards Precision-Phenotyping of Behavior in ASD

Background: There is a critical need for precision phenotyping across neurodevelopmental disorders, especially in individuals who receive a clinical diagnosis of autism spectrum disorder (ASD). Phelan-McDermid deletion syndrome (PMS) is one such example, as it has a high penetrance of ASD. At present, no biometric characterization of the behavioral phenotype within PMS exists.Methods: We introduce a data-type and statistical framework that permits the personalized profiling of naturalistic behaviors. Walking patterns were assessed in 30 participants (16 PMS, 3 idiopathic-ASD and 11 age- and sex-matched controls). Each individual's micro-movement signatures were recorded at 240 Hz. We empirically estimated the parameters of the continuous Gamma family of probability distributions and calculated their ranges. These estimated stochastic signatures were then mapped on the Gamma plane to obtain several statistical indexes for each child. To help visualize complex patterns across the cohort, we introduce new tools that enable the assessment of connectivity and modularity indexes across the peripheral network of rotational joints.Results: Typical walking signatures are absent in all children with PMS as well as in the children with idiopathic-ASD (iASD). Underlying these patterns are atypical leg rotational acceleration signatures that render participants with PMS unstable with rotations that are much faster than controls. The median values of the estimated Gamma parameters serve as a cutoff to automatically separate children with PMS 5–7 years old from adolescents with PMS 12–16 years old, the former displaying more randomness and larger noise. The fluctuations in the arm's motions during the walking also have atypical statistics that separate males from females in PMS and show higher rates of noise accumulation in idiopathic ASD (iASD) children. Despite high heterogeneity, all iASD children have excess noise, a narrow range of probability-distribution shapes across the body joints and a distinct joint network connectivity pattern. Both PMS and iASD have systemic issues with noise in micro-motions across the body with specific signatures for each child that, as a cohort, selectively deviates from controls.Conclusions: We provide a new methodology for precision behavioral phenotyping with the potential to use micro-movement output noise as a natural classifier of neurodevelopmental disorders of known etiology. This approach may help us better understand idiopathic neurodevelopmental disorders and personalize the assessments of natural movements in these populations.

Higher Dimensional Meta-State Analysis Reveals Reduced Resting fMRI Connectivity Dynamism in Schizophrenia Patients.

Resting-state functional brain imaging studies of network connectivity have long assumed that functional connections are stationary on the timescale of a typical scan. Interest in moving beyond this simplifying assumption has emerged only recently. The great hope is that training the right lens on time-varying properties of whole-brain network connectivity will shed additional light on previously concealed brain activation patterns characteristic of serious neurological or psychiatric disorders. We present evidence that multiple explicitly dynamical properties of time-varying whole-brain network connectivity are strongly associated with schizophrenia, a complex mental illness whose symptomatic presentation can vary enormously across subjects. As with so much brain-imaging research, a central challenge for dynamic network connectivity lies in determining transformations of the data that both reduce its dimensionality and expose features that are strongly predictive of important population characteristics. Our paper introduces an elegant, simple method of reducing and organizing data around which a large constellation of mutually informative and intuitive dynamical analyses can be performed. This framework combines a discrete multidimensional data-driven representation of connectivity space with four core dynamism measures computed from large-scale properties of each subject’s trajectory, ie., properties not identifiable with any specific moment in time and therefore reasonable to employ in settings lacking inter-subject time-alignment, such as resting-state functional imaging studies. Our analysis exposes pronounced differences between schizophrenia patients (Nsz = 151) and healthy controls (Nhc = 163). Time-varying whole-brain network connectivity patterns are found to be markedly less dynamically active in schizophrenia patients, an effect that is even more pronounced in patients with high levels of hallucinatory behavior. To the best of our knowledge this is the first demonstration that high-level dynamic properties of whole-brain connectivity, generic enough to be commensurable under many decompositions of time-varying connectivity data, exhibit robust and systematic differences between schizophrenia patients and healthy controls.

Early Development of Functional Network Segregation Revealed by Connectomic Analysis of the Preterm Human Brain.

Human brain functional networks are topologically organized with nontrivial connectivity characteristics such as small-worldness and densely linked hubs to support highly segregated and integrated information processing. However, how they emerge and change at very early developmental phases remains poorly understood. Here, we used resting-state functional MRI and voxel-based graph theory analysis to systematically investigate the topological organization of whole-brain networks in 40 infants aged around 31 to 42 postmenstrual weeks. The functional connectivity strength and heterogeneity increased significantly in primary motor, somatosensory, visual, and auditory regions, but much less in high-order default-mode and executive-control regions. The hub and rich-club structures in primary regions were already present at around 31 postmenstrual weeks and exhibited remarkable expansions with age, accompanied by increased local clustering and shortest path length, indicating a transition from a relatively random to a more organized configuration. Moreover, multivariate pattern analysis using support vector regression revealed that individual brain maturity of preterm babies could be predicted by the network connectivity patterns. Collectively, we highlighted a gradually enhanced functional network segregation manner in the third trimester, which is primarily driven by the rapid increases of functional connectivity of the primary regions, providing crucial insights into the topological development patterns prior to birth.

Anatomically Detailed and Large-Scale Simulations Studying Synapse Loss and Synchrony Using NeuroBox.

The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function. Development in the area of synthetic neural network generation and morphology reconstruction from microscopy data has brought forth the software tool NeuGen. Coupling this morphology data (either from databases, synthetic, or reconstruction) to the simulation platform UG 4 (which harbors a neuroscientific portfolio) and VRL-Studio, has brought forth the extendible toolbox NeuroBox. NeuroBox allows users to perform numerical simulations on hybrid-dimensional morphology representations. The code basis is designed in a modular way, such that e.g., new channel or synapse types can be added to the library. Workflows can be specified through scripts or through the VRL-Studio graphical workflow representation. Third-party tools, such as ImageJ, can be added to NeuroBox workflows. In this paper, NeuroBox is used to study the electrical and biochemical effects of synapse loss vs. synchrony in neurons, to investigate large morphology data sets within detailed biophysical simulations, and used to demonstrate the capability of utilizing high-performance computing infrastructure for large scale network simulations. Using new synapse distribution methods and Finite Volume based numerical solvers for compartment-type models, our results demonstrate how an increase in synaptic synchronization can compensate synapse loss at the electrical and calcium level, and how detailed neuronal morphology can be integrated in large-scale network simulations.

Children with well controlled epilepsy possess different spatio-temporal patterns of causal network connectivity during a visual working memory task.

Using spectral Granger causality (GC) we identified distinct spatio-temporal causal connectivity (CC) patterns in groups of control and epileptic children during the execution of a one-back matching visual discrimination working memory task. Differences between control and epileptic groups were determined for both GO and NOGO conditions. The analysis was performed on a set of 19-channel EEG cortical activity signals. We show that for the GO task, the highest brain activity in terms of the density of the CC networks is observed in α band for the control group while for the epileptic group the CC network seems disrupted as reflected by the small number of connections. For the NOGO task, the denser CC network was observed in θ band for the control group while widespread differences between the control and the epileptic group were located bilaterally at the left temporal-midline and parietal areas. In order to test the discriminative power of our analysis, we performed a pattern analysis approach based on fuzzy classification techniques. The performance of the classification scheme was evaluated using permutation tests. The analysis demonstrated that, on average, 87.6% of the subjects were correctly classified in control and epileptic. Thus, our findings may provide a helpful insight on the mechanisms pertaining to the cognitive response of children with well controlled epilepsy and could potentially serve as "functional" biomarkers for early diagnosis.

Interaction between Road Network Connectivity and Spatial Pattern

Road network is considered to be one of the keys to regional development of a region. The huge developmental cost of the road network demands effective utilisation, which can be attained only when there is proper connectivity and orientation. But the road network in many urban areas develop in an organic growth pattern. Hence a great emphasis needs to be given to the connectivity pattern of the road network. Urban road network has less theoretical research. Only some developed countries have carried out the evaluation of urban road network and hence it has great potential for development and application prospects.In this study an attempt has been made to analyse the road network connectivity and spatial pattern existing in Calicut city in India, and hence to determine if the network connectivity can explain significant variance in the spatial pattern of the network structure. Analysis reveals that transport network fractality is directly varying with respect to connectivity and coverage of the study area. Network density could better predict fractality of the road network than any other connectivity indicators. This means that there is significant relationship between the level of road network development and the network spatial structure within the study area.

Dynamic Network Drivers of Seizure Generation, Propagation and Termination in Human Neocortical Epilepsy.

The epileptic network is characterized by pathologic, seizure-generating ‘foci’ embedded in a web of structural and functional connections. Clinically, seizure foci are considered optimal targets for surgery. However, poor surgical outcome suggests a complex relationship between foci and the surrounding network that drives seizure dynamics. We developed a novel technique to objectively track seizure states from dynamic functional networks constructed from intracranial recordings. Each dynamical state captures unique patterns of network connections that indicate synchronized and desynchronized hubs of neural populations. Our approach suggests that seizures are generated when synchronous relationships near foci work in tandem with rapidly changing desynchronous relationships from the surrounding epileptic network. As seizures progress, topographical and geometrical changes in network connectivity strengthen and tighten synchronous connectivity near foci—a mechanism that may aid seizure termination. Collectively, our observations implicate distributed cortical structures in seizure generation, propagation and termination, and may have practical significance in determining which circuits to modulate with implantable devices.

Analysis of Stage-Specific Gene Expression Profiles in the Uterine Endometrium during Pregnancy in Pigs.

The uterine endometrium plays a critical role in regulating the estrous cycle and the establishment and maintenance of pregnancy in mammalian species. Many studies have investigated the expression and function of genes in the uterine endometrium, but the global expression pattern of genes and relationships among genes differentially expressed in the uterine endometrium during gestation in pigs remain unclear. Thus, this study investigated global gene expression profiles using microarray in pigs. Diverse transcriptome analyses including clustering, network, and differentially expressed gene (DEG) analyses were performed to detect endometrial gene expression changes during the different gestation stages. In total, 6,991 genes were found to be differentially expressed by comparing genes expressed on day (D) 12 of pregnancy with those on D15, D30, D60, D90 and D114 of pregnancy, and clustering analysis of detected DEGs distinguished 8 clusters. Furthermore, several pregnancy-related hub genes such as ALPPL2, RANBP17, NF1B, SPP1, and CST6 were discovered through network analysis. Finally, detected hub genes were technically validated by quantitative RT-PCR. These results suggest the complex network characteristics involved in uterine endometrial gene expression during pregnancy and indicate that diverse patterns of stage-specific gene expression and network connections may play a critical role in endometrial remodeling and in placental and fetal development to establish and maintenance of pregnancy in pigs.

In Vivo Mapping of Cortical Columnar Networks in the Monkey with Focal Electrical and Optical Stimulation.

There are currently largescale efforts to understand the brain as a connection machine. However, there has been little emphasis on understanding connection patterns between functionally specific cortical columns. Here, we review development and application of focal electrical and optical stimulation methods combined with optical imaging and fMRI mapping in the non-human primate. These new approaches, when applied systematically on a large scale, will elucidate functionally specific intra-areal and inter-areal network connection patterns. Such functionally specific network data can provide accurate views of brain network topology.

Spontaneous functional network dynamics and associated structural substrates in the human brain.

Recent imaging connectomics studies have demonstrated that the spontaneous human brain functional networks derived from resting-state functional MRI (R-fMRI) include many non-trivial topological properties, such as highly efficient small-world architecture and densely connected hub regions. However, very little is known about dynamic functional connectivity (D-FC) patterns of spontaneous human brain networks during rest and about how these spontaneous brain dynamics are constrained by the underlying structural connectivity. Here, we combined sub-second multiband R-fMRI data with graph-theoretical approaches to comprehensively investigate the dynamic characteristics of the topological organization of human whole-brain functional networks, and then employed diffusion imaging data in the same participants to further explore the associated structural substrates. At the connection level, we found that human whole-brain D-FC patterns spontaneously fluctuated over time, while homotopic D-FC exhibited high connectivity strength and low temporal variability. At the network level, dynamic functional networks exhibited time-varying but evident small-world and assortativity architecture, with several regions (e.g., insula, sensorimotor cortex and medial prefrontal cortex) emerging as functionally persistent hubs (i.e., highly connected regions) while possessing large temporal variability in their degree centrality. Finally, the temporal characteristics (i.e., strength and variability) of the connectional and nodal properties of the dynamic brain networks were significantly associated with their structural counterparts. Collectively, we demonstrate the economical, efficient, and flexible characteristics of dynamic functional coordination in large-scale human brain networks during rest, and highlight their relationship with underlying structural connectivity, which deepens our understandings of spontaneous brain network dynamics in humans.

Distributions of Irritative Zones Are Related to Individual Alterations of Resting-State Networks in Focal Epilepsy.

Alterations in the connectivity patterns of the fMRI-based resting-state networks (RSNs) have been reported in several types of epilepsies. Evidence pointed out these alterations might be associated with the genesis and propagation of interictal epileptiform discharges (IEDs). IEDs also evoke blood-oxygen-level dependent (BOLD) responses, which have been used to delineate irritative zones during preoperative work-up. Therefore, one may expect a relationship between the topology of the IED-evoked BOLD response network and the altered spatial patterns of the RSNs. In this study, we used EEG recordings and fMRI data obtained simultaneously from a chronic model of focal epilepsy in Wistar rats to verify our hypothesis. We found that IED-evoked BOLD response networks comprise both cortical and subcortical structures with a rat-dependent topology. In all rats, IEDs evoke both activation and deactivation types of BOLD responses. Using a Granger causality method, we found that in many cases areas with BOLD deactivation have directed influences on areas with activation (p<0.05). We were able to predict topological properties (i.e., focal/diffused, unilateral/bilateral) of the IED-evoked BOLD response network by performing hierarchical clustering analysis on major spatial features of the RSNs. All these results suggest that IEDs and disruptions in the RSNs found previously in humans may be different manifestations of the same transient events, probably reflecting altered consciousness. In our opinion, the shutdown of specific nodes of the default mode network may cause uncontrollable excitability in other functionally connected brain areas. We conclude that IED-evoked BOLD responses (i.e., activation and deactivation) and alterations of RSNs are intrinsically related, and speculate that an understanding of their interplay is necessary to discriminate focal epileptogenesis and network propagation phenomena across different brain modules via hub-based connectivity.