Analysis Of Functional Brain Networks Research Articles

On the danger of detecting network states in white noise.

On the danger of detecting network states in white noise.

The age-related posterior-anterior shift as revealed by voxelwise analysis of functional brain networks.

The posterior-anterior shift in aging (PASA) is a commonly observed phenomenon in functional neuroimaging studies of aging, characterized by age-related reductions in occipital activity alongside increases in frontal activity. In this work we have investigated the hypothesis as to whether the PASA is also manifested in functional brain network measures such as degree, clustering coefficient, path length and local efficiency. We have performed statistical analysis upon functional networks derived from a fMRI dataset containing data from healthy young, healthy aged, and aged individuals with very mild to mild Alzheimer's disease (AD). Analysis of both task based and resting state functional network properties has indicated that the PASA can also be characterized in terms of modulation of functional network properties, and that the onset of AD appears to accentuate this modulation. We also explore the effect of spatial normalization upon the results of our analysis.

Graph analysis of functional brain networks: practical issues in translational neuroscience.

The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective, communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires the know-how of all the methodological steps of the pipeline that manipulate the input brain signals and extract the functional network properties. On the other hand, knowledge of the neural phenomenon under study is required to perform physiologically relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes.

Data driven analysis of functional brain networks in fMRI for schizophrenia investigation

ABSTRACTThe purpose of this article is to present a methodology to identify the sources of activity in brain networks from functional magnetic resonance imaging (fMRI) data using the multiset canonical correlation analysis algorithm. The aim is to lay the foundations for a screening marker to be used as indicator of mental diseases. Group analysis blind source separation methods have proved reliable to extract the latent sources underlying the brain activities but currently there is no recognized biomarker for mental disorders. Recent studies have identified alterations in the so called default mode network (DMN) that are common to several neuropsychiatric disorders, including schizophrenia. In particular, here we account for the hypothesis that the alterations in the DMN activity can be effectively highlighted by analyzing the transient states between two different tasks. A set of fMRI data acquired from 18 subjects performing working memory tasks is investigated for such purpose. Subjects are patients affected by schizophrenia for one half and healthy control subjects for the other. Under these conditions, the proposed methodology provides high discrimination performances in terms of classification error, thereby providing promising results for a preliminary tool able to monitor the disease state or to perform a prescreening for patients at risk for schizophrenia. © 2014 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 24, 239–248, 2014

Network modulation following sham surgery in Parkinson's disease.

Patient responses to placebo and sham effects are a major obstacle to the development of therapies for brain disorders, including Parkinson's disease (PD). Here, we used functional brain imaging and network analysis to study the circuitry underlying placebo effects in PD subjects randomized to sham surgery as part of a double-blind gene therapy trial. Metabolic imaging was performed prior to randomization, then again at 6 and 12 months after sham surgery. In this cohort, the sham response was associated with the expression of a distinct cerebello-limbic circuit. The expression of this network increased consistently in patients blinded to treatment and correlated with independent clinical ratings. Once patients were unblinded, network expression declined toward baseline levels. Analogous network alterations were not seen with open-label levodopa treatment or during disease progression. Furthermore, sham outcomes in blinded patients correlated with baseline network expression, suggesting the potential use of this quantitative measure to identify "sham-susceptible" subjects before randomization. Indeed, Monte Carlo simulations revealed that a priori exclusion of such individuals substantially lowers the number of randomized participants needed to demonstrate treatment efficacy. Individualized subject selection based on a predetermined network criterion may therefore limit the need for sham interventions in future clinical trials.

Dynamic Repertoire of Intrinsic Brain States Is Reduced in Propofol-Induced Unconsciousness

The richness of conscious experience is thought to scale with the size of the repertoire of causal brain states, and it may be diminished in anesthesia. We estimated the state repertoire from dynamic analysis of intrinsic functional brain networks in conscious sedated and unconscious anesthetized rats. Functional resonance images were obtained from 30-min whole-brain resting-state blood oxygen level-dependent (BOLD) signals at propofol infusion rates of 20 and 40 mg/kg/h, intravenously. Dynamic brain networks were defined at the voxel level by sliding window analysis of regional homogeneity (ReHo) or coincident threshold crossings (CTC) of the BOLD signal acquired in nine sagittal slices. The state repertoire was characterized by the temporal variance of the number of voxels with significant ReHo or positive CTC. From low to high propofol dose, the temporal variances of ReHo and CTC were reduced by 78% ± 20% and 76%± 20%, respectively. Both baseline and propofol-induced reduction of CTC temporal variance increased from lateral to medial position. Group analysis showed a 20% reduction in the number of unique states at the higher propofol dose. Analysis of temporal variance in 12 anatomically defined regions of interest predicted that the largest changes occurred in visual cortex, parietal cortex, and caudate-putamen. The results suggest that the repertoire of large-scale brain states derived from the spatiotemporal dynamics of intrinsic networks is substantially reduced at an anesthetic dose associated with loss of consciousness.

Graph Theory Analysis of Functional Brain Networks and Mobility Disability in Older Adults

The brain's structural integrity is associated with mobility function in older adults. Changes in function may be evident earlier than changes in structure and may be more directly related to mobility. Therefore, we assessed whether functional brain networks varied with mobility function in older adults. Short Physical Performance Battery (SPPB) and resting state functional magnetic resonance imaging were collected on 24 young (mean age = 26.4±5.1) and 48 older (mean age = 72.04±5.1) participants. Older participants were divided into three groups by SPPB score: Low SPPB (score = 7-9), Mid SPPB (score = 10), High SPPB (score = 11-12).Graph theory-based methods were used to characterize and compare brain network organization. Connectivity in the somatomotor cortex distinguished between groups based on SPPB score. The community structure of the somatomotor cortex was significantly less consistent in the Low SPPB group (mean = 0.097±0.05) compared with Young (mean = 0.163±0.09, p = .03) SPPB group. Striking differences were evident in second-order connections between somatomotor cortex and superior temporal gyrus and insula that reached statistical significance. The Low SPPB group (mean = 140.87±109.30) had a significantly higher number of connections than Young (mean = 45.05±33.79, p = .0003) or High (mean = 49.61±35.31, p = .002) SPPB group. Older adults with poorer mobility function exhibited reduced consistency of somatomotor community structure and a greater number of secondary connections with vestibular and multisensory regions of the brain. Further study is needed to fully interpret these effects, but analysis of functional brain networks adds new insights to the contribution of the brain to mobility.

Phase synchrony in the cerebral infarction electroencephalogram based on the degree of network-links

Recently, there has been increasing interest in applying graph theory to the quantitative analysis of brain functional networks, while phase synchronization (PS) analysis has been demonstrated to be a useful method to infer functional connectivity with multichannel neural signals, e.g., electroencephalogram (EEG). In this paper, we focus on the case that the number of channels in EEG data is not adequate for the use of graph theory analysis. The degree of network-links (DNLs), an index based on the PS analysis of all the EEG wave pairs, is proposed to study the relevant and the overall characteristics of the brain. With the help of a novel division to the frequency range 0.5–30 Hz, we analyze the DNLs in different frequency bands of the EEG signals. As a comparison, a frequency band analysis of the relative power spectrum is conducted. The results demonstrate that when the cerebral infarction (CI) patients and normal control people are analyzed, there is a need for the reasonable length of EEG data to quantify the differences between different dynamical systems; under a reasonable data length, the frequency band (19–24 Hz) yields the best accuracy for diagnosing CI, which lies within the classical beta band (13–30 Hz); furthermore, only in the 19–24 Hz band, as for the values of relative power spectrum, in each EEG channel, there presents a similar relationship between the CI group and control group. The experimental results suggest that 19–24 Hz should be the optimal range for the diagnosis of CI, further the DNLs calculated within this band serve as an assist indicator in the CI diagnosis.

Change Detection and Visualization of Functional Brain Networks using EEG Data

Mining dynamic and non-trivial patterns of interactions of functional brain networks has gained significance due to the recent advances in the field of computational neuroscience. Sophisticated data search capabilities, advanced signal processing techniques, statistical methods, complex network and graph mining algorithms to unfold and discover hidden patterns in the functional brain network supported with efficient visualization techniques are essential for making potential inferences of the results obtained. Visualization of change in activity during cognitive function is useful to discover and get insights into the hidden, novel and complex neuronal patterns and trends during the normal and cognitive load conditions from the graph/temporal representation of the functional brain network. This paper explores novel methods to detect and track the dynamics and complexity of the brain function. It also uses a new tool called Functional Brain Network Analysis and Visualization (FBNAV) tool to visualize the outcomes of various computational analyses to enable us to identify and study the changing neuronal patterns during various states of the brain activity using augmented/customisedTopoplots andHeadplots. The change detection algorithm tracks and visualizes the cognitive load induced changes across the scalp regions.These techniques may also be helpful to locate and identify patterns in certain abnormal mental states resulting due to some mental disorders such as stress.

Reconstructing functional brain networks: have we got the basics right?

Both at rest and during the executions of cognitive tasks, the brain continuously creates and reshapes complex patterns of correlated dynamics. Thus, brain functional activity is naturally described in terms of networks, i.e., sets of nodes, representing distinct subsystems, and links connecting node pairs, representing relationships between them. Recently, brain function has started being investigated using a statistical physics understanding of graph theory, an old branch of pure mathematics (Newman, 2010). Within this framework, network properties are independent of the identity of their nodes, as they emerge in a non-trivial way from their interactions. Observed topologies are instances of a network ensemble, falling into one of few universality classes and are therefore inherently statistical in nature. Functional network reconstruction comprises various steps: first, nodes are identified; then, links are established according to a certain metric. This gives rise to a clique with an all-to-all connectivity. Deciding which links are significant is done by choosing which values of these metrics should be taken into account. Finally, network properties are computed and used to characterize the network. Each of these steps contains an element of arbitrariness, as graph theory allows characterizing systems once a network is reconstructed, but is neutral as to what should be treated as a system and to how to isolate its constituent parts. Here we discuss some aspects related to the way nodes, links and networks in general are defined in system-level studies using noninvasive techniques, which may be critical when interpreting the results of functional brain network analyses.

Building and Clustering Analysis of Brain Functional Network in Acupuncture

Aimed at exploring the mechanism of acupuncture therapy, we develop functional brain networks using electroencephalogram (EEG) data, and use the methods cluster coefficient to analyze the functional networks. We develop the following result: during the acupuncture, the structure of network becomes tighter, the relativity grows stronger and the structure of the networks becomes complex. Our conclusion is that acupuncture is able to affect the firing properties of the central nervous system, and make the information transmission in the brain functional sections stronger.

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.

Defining nodes in complex brain networks

Network science holds great promise for expanding our understanding of the human brain in health, disease, development, and aging. Network analyses are quickly becoming the method of choice for analyzing functional MRI data. However, many technical issues have yet to be confronted in order to optimize results. One particular issue that remains controversial in functional brain network analyses is the definition of a network node. In functional brain networks a node represents some predefined collection of brain tissue, and an edge measures the functional connectivity between pairs of nodes. The characteristics of a node, chosen by the researcher, vary considerably in the literature. This manuscript reviews the current state of the art based on published manuscripts and highlights the strengths and weaknesses of three main methods for defining nodes. Voxel-wise networks are constructed by assigning a node to each, equally sized brain area (voxel). The fMRI time-series recorded from each voxel is then used to create the functional network. Anatomical methods utilize atlases to define the nodes based on brain structure. The fMRI time-series from all voxels within the anatomical area are averaged and subsequently used to generate the network. Functional activation methods rely on data from traditional fMRI activation studies, often from databases, to identify network nodes. Such methods identify the peaks or centers of mass from activation maps to determine the location of the nodes. Small (~10–20 millimeter diameter) spheres located at the coordinates of the activation foci are then applied to the data being used in the network analysis. The fMRI time-series from all voxels in the sphere are then averaged, and the resultant time series is used to generate the network. We attempt to clarify the discussion and move the study of complex brain networks forward. While the “correct” method to be used remains an open, possibly unsolvable question that deserves extensive debate and research, we argue that the best method available at the current time is the voxel-wise method.

Analyzing complex functional brain networks: Fusing statistics and network science to understand the brain*†

Complex functional brain network analyses have exploded over the last decade, gaining traction due to their profound clinical implications. The application of network science (an interdisciplinary offshoot of graph theory) has facilitated these analyses and enabled examining the brain as an integrated system that produces complex behaviors. While the field of statistics has been integral in advancing activation analyses and some connectivity analyses in functional neuroimaging research, it has yet to play a commensurate role in complex network analyses. Fusing novel statistical methods with network-based functional neuroimage analysis will engender powerful analytical tools that will aid in our understanding of normal brain function as well as alterations due to various brain disorders. Here we survey widely used statistical and network science tools for analyzing fMRI network data and discuss the challenges faced in filling some of the remaining methodological gaps. When applied and interpreted correctly, the fusion of network scientific and statistical methods has a chance to revolutionize the understanding of brain function.

Structure out of chaos: Functional brain network analysis with EEG, MEG, and functional MRI

The brain is the characteristic of a complex structure. By representing brain function, measured with EEG, MEG, and fMRI, as an abstract network, methods for the study of complex systems can be applied. These network studies have revealed insights in the complex, yet organized, architecture that is evidently present in brain function. We will discuss some technical aspects of formation and assessment of the functional brain networks. Moreover, the results that have been reported in this respect in the last years, in healthy brains as well as in functional brain networks of subjects with a neurological or psychiatrical disease, will be reviewed.

GAT: a graph-theoretical analysis toolbox for analyzing between-group differences in large-scale structural and functional brain networks.

In recent years, graph theoretical analyses of neuroimaging data have increased our understanding of the organization of large-scale structural and functional brain networks. However, tools for pipeline application of graph theory for analyzing topology of brain networks is still lacking. In this report, we describe the development of a graph-analysis toolbox (GAT) that facilitates analysis and comparison of structural and functional network brain networks. GAT provides a graphical user interface (GUI) that facilitates construction and analysis of brain networks, comparison of regional and global topological properties between networks, analysis of network hub and modules, and analysis of resilience of the networks to random failure and targeted attacks. Area under a curve (AUC) and functional data analyses (FDA), in conjunction with permutation testing, is employed for testing the differences in network topologies; analyses that are less sensitive to the thresholding process. We demonstrated the capabilities of GAT by investigating the differences in the organization of regional gray-matter correlation networks in survivors of acute lymphoblastic leukemia (ALL) and healthy matched Controls (CON). The results revealed an alteration in small-world characteristics of the brain networks in the ALL survivors; an observation that confirm our hypothesis suggesting widespread neurobiological injury in ALL survivors. Along with demonstration of the capabilities of the GAT, this is the first report of altered large-scale structural brain networks in ALL survivors.

Functional Brain Networks: beyond the small-world paradigm

This contribution reviews the current state of the art comprising the application of Complex Networks Theory to the analysis of functional brain networks. We briefly overview the main advances in this field during the last decade and we explain how graph analysis has increased our knowledge about how the brain behaves when performing a specific task or how it fails when a certain pathology arises. We also show the limitations of this kind of analysis, which have been a source of confusion and misunderstanding when interpreting the results obtained. Finally, we discuss possible future directions for the years to come.

Measuring Granger Causality between Cortical Regions from Voxelwise fMRI BOLD Signals with LASSO

Functional brain network studies using the Blood Oxygen-Level Dependent (BOLD) signal from functional Magnetic Resonance Imaging (fMRI) are becoming increasingly prevalent in research on the neural basis of human cognition. An important problem in functional brain network analysis is to understand directed functional interactions between brain regions during cognitive performance. This problem has important implications for understanding top-down influences from frontal and parietal control regions to visual occipital cortex in visuospatial attention, the goal motivating the present study. A common approach to measuring directed functional interactions between two brain regions is to first create nodal signals by averaging the BOLD signals of all the voxels in each region, and to then measure directed functional interactions between the nodal signals. Another approach, that avoids averaging, is to measure directed functional interactions between all pairwise combinations of voxels in the two regions. Here we employ an alternative approach that avoids the drawbacks of both averaging and pairwise voxel measures. In this approach, we first use the Least Absolute Shrinkage Selection Operator (LASSO) to pre-select voxels for analysis, then compute a Multivariate Vector AutoRegressive (MVAR) model from the time series of the selected voxels, and finally compute summary Granger Causality (GC) statistics from the model to represent directed interregional interactions. We demonstrate the effectiveness of this approach on both simulated and empirical fMRI data. We also show that averaging regional BOLD activity to create a nodal signal may lead to biased GC estimation of directed interregional interactions. The approach presented here makes it feasible to compute GC between brain regions without the need for averaging. Our results suggest that in the analysis of functional brain networks, careful consideration must be given to the way that network nodes and edges are defined because those definitions may have important implications for the validity of the analysis.

Graph analysis of functional brain networks for cognitive control of action in traumatic brain injury

Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly dispersed frontal and parietal activity during performance of cognitive control tasks. We constructed binary and weighted functional networks and calculated their topological properties using a graph theoretical approach. Twenty-three adults with traumatic brain injury and 26 age-matched controls were instructed to switch between coordination modes while making spatially and temporally coupled circular motions with joysticks during event-related functional magnetic resonance imaging. Results demonstrated that switching performance was significantly lower in patients with traumatic brain injury compared with control subjects. Furthermore, although brain networks of both groups exhibited economical small-world topology, altered functional connectivity was demonstrated in patients with traumatic brain injury. In particular, compared with controls, patients with traumatic brain injury showed increased connectivity degree and strength, and higher values of local efficiency, suggesting adaptive mechanisms in this group. Finally, the degree of increased connectivity was significantly correlated with poorer switching task performance and more severe brain injury. We conclude that analysing the functional brain network connectivity provides new insights into understanding cognitive control changes following brain injury.

Different brain networks underlying the acquisition and expression of contextual fear conditioning: a metabolic mapping study

The specific brain regions and circuits involved in the acquisition and expression of contextual fear conditioning are still a matter of debate. To address this issue, regional changes in brain metabolic capacity were mapped during the acquisition and expression of contextual fear conditioning using cytochrome oxidase (CO) quantitative histochemistry. In comparison with a group briefly exposed to a conditioning chamber, rats that received a series of randomly presented footshocks in the same conditioning chamber (fear acquisition group) showed increased CO activity in anxiety-related brain regions like the ventral periaqueductal gray, the ventral hippocampus, the lateral habenula, the mammillary bodies, and the laterodorsal thalamic nucleus. Another group received randomly presented footshocks, and it was re-exposed to the same conditioning chamber one week later (fear expression group). The conditioned group had significantly higher CO activity as compared with the matched control group in the following brain regions: the ventral periaqueductal gray, the central and lateral nuclei of the amygdala, and the bed nucleus of the stria terminalis. In addition, analysis of functional brain networks using interregional CO activity correlations revealed different patterns of functional connectivity between fear acquisition and fear expression groups. In particular, a network comprising the ventral hippocampus and amygdala nuclei was found in the fear acquisition group, whereas a closed reciprocal dorsal hippocampal network was detected in the fear expression group. These results suggest that contextual fear acquisition and expression differ as regards to the brain networks involved, although they share common brain regions involved in fear, anxiety, and defensive behavior.