Human Brain Functional Networks Research Articles

Trajectories of human brain functional connectome maturation across the birth transition.

Understanding the sequence and timing of brain functional network development at the beginning of human life is critically important from both normative and clinical perspectives. Yet, we presently lack rigorous examination of the longitudinal emergence of human brain functional networks over the birth transition. Leveraging a large, longitudinal perinatal functional magnetic resonance imaging (fMRI) data set, this study models developmental trajectories of brain functional networks spanning 25 to 55 weeks of post-conceptual gestational age (GA). The final sample includes 126 fetal scans (GA = 31.36 ± 3.83 weeks) and 58 infant scans (GA = 48.17 ± 3.73 weeks) from 140 unique subjects. In this study, we document the developmental changes of resting-state functional connectivity (RSFC) over the birth transition, evident at both network and graph levels. We observe that growth patterns are regionally specific, with some areas showing minimal RSFC changes, while others exhibit a dramatic increase at birth. Examples with birth-triggered dramatic change include RSFC within the subcortical network, within the superior frontal network, within the occipital-cerebellum joint network, as well as the cross-hemisphere RSFC between the bilateral sensorimotor networks and between the bilateral temporal network. Our graph analysis further emphasized the subcortical network as the only region of the brain exhibiting a significant increase in local efficiency around birth, while a concomitant gradual increase was found in global efficiency in sensorimotor and parietal-frontal regions throughout the fetal to neonatal period. This work unveils fundamental aspects of early brain development and lays the foundation for future work on the influence of environmental factors on this process.

Human adolescent brain similarity development is different for paralimbic versus neocortical zones

Adolescent development of human brain structural and functional networks is increasingly recognized as fundamental to emergence of typical and atypical adult cognitive and emotional proodal magnetic resonance imaging (MRI) data collected from N [Formula: see text] 300 healthy adolescents (51%; female; 14 to 26 y) each scanned repeatedly in an accelerated longitudinal design, to provide an analyzable dataset of 469 structural scans and 448 functional MRI scans. We estimated the morphometric similarity between each possible pair of 358 cortical areas on a feature vector comprising six macro- and microstructural MRI metrics, resulting in a morphometric similarity network (MSN) for each scan. Over the course of adolescence, we found that morphometric similarity increased in paralimbic cortical areas, e.g., insula and cingulate cortex, but generally decreased in neocortical areas, and these results were replicated in an independent developmental MRI cohort (N [Formula: see text] 304). Increasing hubness of paralimbic nodes in MSNs was associated with increased strength of coupling between their morphometric similarity and functional connectivity. Decreasing hubness of neocortical nodes in MSNs was associated with reduced strength of structure-function coupling and increasingly diverse functional connections in the corresponding fMRI networks. Neocortical areas became more structurally differentiated and more functionally integrative in a metabolically expensive process linked to cortical thinning and myelination, whereas paralimbic areas specialized for affective and interoceptive functions became less differentiated, as hypothetically predicted by a developmental transition from periallocortical to proisocortical organization of the cortex. Cytoarchitectonically distinct zones of the human cortex undergo distinct neurodevelopmental programs during typical adolescence.

A Hybrid Routing Pattern in Human Brain Structural Network Revealed By Evolutionary Computation.

The human brain functional connectivity network (FCN) is constrained and shaped by the communication processes in the structural connectivity network (SCN). The underlying communication mechanism thus becomes a critical issue for understanding the formation and organization of the FCN. A number of communication models supported by different routing strategies have been proposed, with shortest path (SP), random diffusion (DIF), and spatial navigation (NAV) as the most typical, respectively requiring network global knowledge, local knowledge, and both for path seeking. Yet these models all assumed every brain region to use one routing strategy uniformly, ignoring convergent evidence that supports the regional heterogeneity in both terms of biological substrates and functional roles. In this regard, the current study developed a hybrid communication model that allowed each brain region to choose a routing strategy from SP, DIF, and NAV independently. A genetic algorithm was designed to uncover the underlying region-wise hybrid routing strategy (namely HYB). The HYB was found to outperform the three typical routing strategies in predicting FCN and facilitating robust communication. Analyses on HYB further revealed that brain regions in lower-order functional modules inclined to route signals using global knowledge, while those in higher-order functional modules preferred DIF that requires only local knowledge. Compared to regions that used global knowledge for routing, regions using DIF had denser structural connections, participated in more functional modules, but played a less dominant role within modules. Together, our findings further evidenced that hybrid routing underpins efficient SCN communication and locally heterogeneous structure-function coupling.

Two common and distinct forms of variation in human functional brain networks.

The cortex has a characteristic layout with specialized functional areas forming distributed large-scale networks. However, substantial work shows striking variation in this organization across people, which relates to differences in behavior. While most previous work treats individual differences as linked to boundary shifts between the borders of regions, here we show that cortical 'variants' also occur at a distance from their typical position, forming ectopic intrusions. Both 'border' and 'ectopic' variants are common across individuals, but differ in their location, network associations, properties of subgroups of individuals, activations during tasks, and prediction of behavioral phenotypes. Border variants also track significantly more with shared genetics than ectopic variants, suggesting a closer link between ectopic variants and environmental influences. This work argues that these two dissociable forms of variation-border shifts and ectopic intrusions-must be separately accounted for in the analysis of individual differences in cortical systems across people.

Coupling Visual Semantics of Artificial Neural Networks and Human Brain Function via Synchronized Activations

Artificial neural networks (ANNs), originally inspired by biological neural networks (BNNs), have achieved remarkable successes in many tasks such as visual representation learning. However, whether there exists semantic correlations/connections between the visual representations in ANNs and those in BNNs remains largely unexplored due to both the lack of an effective tool to link and couple two different domains, and the lack of a general and effective framework for representing the visual semantics in BNNs such as human functional brain networks (FBNs). To answer this question, we propose a novel computational framework, Synchronized Activations (Sync-ACT), to couple the visual representation spaces and semantics between ANNs and BNNs in human brain based on naturalistic functional magnetic resonance imaging (nfMRI) data. With this approach, we are able to semantically annotate the neurons in ANNs with biologically meaningful descriptions derived from human brain imaging for the first time. We evaluated the Sync-ACT framework on two publicly available movie-watching nfMRI datasets. The experiments demonstrate a) the significant correlation and similarity of the semantics between the visual representations in FBNs and those in a variety of convolutional neural networks (CNNs) models; b) the close relationship between CNN’s visual representation similarity to BNNs and its performance in image classification tasks. Overall, our study introduces a general and effective paradigm to couple the ANNs and BNNs and provides novel insights for future studies such as brain-inspired artificial intelligence.

Analysis of Cortico-Muscular Coupling and Functional Brain Network under Different Standing Balance Paradigms.

Maintaining standing balance is essential for people to engage in productive activities in daily life. However, the process of interaction between the cortex and the muscles during balance regulation is understudied. Four balance paradigms of different difficulty were designed by closing eyes and laying sponge pad under feet. Ten healthy subjects were recruited to stand for ten 15 s trials in each paradigm. This study used simultaneously acquired electroencephalography (EEG) and electromyography (EMG) to investigate changes in the human cortico-muscular coupling relationship and functional brain network characteristics during balance control. The coherence and causality of EEG and EMG signals were calculated by magnitude-squared coherence (MSC) and transfer entropy (TE). It was found that changes in balance strategies may lead to a shift in cortico-muscular coherence (CMC) from the beta band to the gamma band when the difficulty of balance increased. As subjects performed the four standing balance paradigms, the causality of the beta band and the gamma band was stronger in the descending neural pathway than that in the ascending neural pathway. A multi-rhythmic functional brain network with 19 EEG channels was constructed and analyzed based on graph theory, showing that its topology also changed with changes in balance difficulty. These results show an active adjustment of the sensorimotor system under different balance paradigms and provide new insights into the endogenous physiological mechanisms underlying the control of standing balance.

Network resilience: impact on small-world network

Lots of complex systems in the real world have network structures, and a number of these structures have small-world property. This kind of structures are called small-world networks. Examples include the world's air transportation system, electric power systems, and human functional brain network, and small-world property is one of the key reasons why these systems function efficiently. However, for complex systems, in addition to their efficiency, resilience or robustness is also one of the concerns, as these systems need to ensure that they do not completely collapse on their own in case of failure of a small number of their components. The purpose of this paper is to try to find and explain the factors that affect the robustness of small-world network by comparing different classes of small-world networks and analysing differences between them and possible causes of these differences, in order to get an idea to optimize the robustness of small-world networks while preserving their small-world property.

Discrete Ricci curvatures capture age-related changes in human brain functional connectivity networks.

Geometry-inspired notions of discrete Ricci curvature have been successfully used as markers of disrupted brain connectivity in neuropsychiatric disorders, but their ability to characterize age-related changes in functional connectivity is unexplored. We apply Forman-Ricci curvature and Ollivier-Ricci curvature to compare functional connectivity networks of healthy young and older subjects from the Max Planck Institute Leipzig Study for Mind-Body-Emotion Interactions (MPI-LEMON) dataset (N = 225). We found that both Forman-Ricci curvature and Ollivier-Ricci curvature can capture whole-brain and region-level age-related differences in functional connectivity. Meta-analysis decoding demonstrated that those brain regions with age-related curvature differences were associated with cognitive domains known to manifest age-related changes-movement, affective processing, and somatosensory processing. Moreover, the curvature values of some brain regions showing age-related differences exhibited correlations with behavioral scores of affective processing. Finally, we found an overlap between brain regions showing age-related curvature differences and those brain regions whose non-invasive stimulation resulted in improved movement performance in older adults. Our results suggest that both Forman-Ricci curvature and Ollivier-Ricci curvature correctly identify brain regions that are known to be functionally or clinically relevant. Our results add to a growing body of evidence demonstrating the sensitivity of discrete Ricci curvature measures to changes in the organization of functional connectivity networks, both in health and disease.

Development of brain state dynamics involved in working memory.

Human functional brain networks are dynamically organized to enable cognitive and behavioral flexibility to meet ever-changing environmental demands. Frontal-parietal network (FPN) and default mode network (DMN) are recognized to play an essential role in executive functions such as working memory. However, little is known about the developmental differences in the brain-state dynamics of these two networks involved in working memory from childhood to adulthood. Here, we implemented Bayesian switching dynamical systems approach to identify brain states of the FPN and DMN during working memory in 69 school-age children and 51 adults. We identified five brain states with rapid transitions, which are characterized by dynamic configurations among FPN and DMN nodes with active and inactive engagement in different task demands. Compared with adults, children exhibited less frequent brain states with the highest activity in FPN nodes dominant to high demand, and its occupancy rate increased with age. Children preferred to attain inactive brain states with low activity in both FPN and DMN nodes. Moreover, children exhibited lower transition probability from low-to-high demand states and such a transition was positively correlated with working memory performance. Notably, higher transition probability from low-to-high demand states was associated with a stronger structural connectivity across FPN and DMN, but with weaker structure-function coupling of these two networks. These findings extend our understanding of how FPN and DMN nodes are dynamically organized into a set of transient brain states to support moment-to-moment information updating during working memory and suggest immature organization of these functional brain networks in childhood, which is constrained by the structural connectivity.

State and Trait Anxiety Share Common Network Topological Mechanisms of Human Brain.

Anxiety is a future-oriented unpleasant and negative mental state induced by distant and potential threats. It could be subdivided into momentary state anxiety and stable trait anxiety, which play a complex and combined role in our mental and physical health. However, no studies have systematically investigated whether these two different dimensions of anxiety share a common or distinct topological mechanism of human brain network. In this study, we used macroscale human brain morphological similarity network and functional connectivity network as well as their spatial and temporal variations to explore the topological properties of state and trait anxiety. Our results showed that state and trait anxiety were both negatively correlated with the coefficient of variation of nodal efficiency in the left frontal eyes field of volume network; state and trait anxiety were both positively correlated with the median and mode of pagerank centrality distribution in the right insula for both static and dynamic functional networks. In summary, our study confirmed that state and trait anxiety shared common human brain network topological mechanisms in the insula and the frontal eyes field, which were involved in preliminary cognitive processing stage of anxiety. Our study also demonstrated that the common brain network topological mechanisms had high spatiotemporal robustness and would enhance our understanding of human brain temporal and spatial organization.

Common variants contribute to intrinsic human brain functional networks.

The human brain forms functional networks of correlated activity, which have been linked with both cognitive and clinical outcomes. However, the genetic variants affecting brain function are largely unknown. Here, we used resting-state functional magnetic resonance images from 47,276 individuals to discover and validate common genetic variants influencing intrinsic brain activity. We identified 45 new genetic regions associated with brain functional signatures (P < 2.8 × 10-11), including associations to the central executive, default mode, and salience networks involved in the triple-network model of psychopathology. A number of brain activity-associated loci colocalized with brain disorders (e.g., the APOE ε4 locus with Alzheimer's disease). Variation in brain function was genetically correlated with brain disorders, such as major depressive disorder and schizophrenia. Together, our study provides a step forward in understanding the genetic architecture of brain functional networks and their genetic links to brain-related complex traits and disorders.

The overlapping modular organization of human brain functional networks across the adult lifespan

Previous studies have demonstrated that the brain functional modular organization, which is a fundamental feature of the human brain, would change along the adult lifespan. However, these studies assumed that each brain region belonged to a single functional module, although there has been convergent evidence supporting the existence of overlap among functional modules in the human brain. To reveal how age affects the overlapping functional modular organization, this study applied an overlapping module detection algorithm that requires no prior knowledge to the resting-state fMRI data of a healthy cohort (N = 570) aged from 18 to 88 years old. A series of measures were derived to delineate the characteristics of the overlapping modular structure and the set of overlapping nodes (brain regions participating in two or more modules) identified from each participant. Age-related regression analyses on these measures found linearly decreasing trends in the overlapping modularity and the modular similarity. The number of overlapping nodes was found increasing with age, but the increment was not even over the brain. In addition, across the adult lifespan and within each age group, the nodal overlapping probability consistently had positive correlations with both functional gradient and flexibility. Further, by correlation and mediation analyses, we showed that the influence of age on memory-related cognitive performance might be explained by the change in the overlapping functional modular organization. Together, our results revealed age-related decreased segregation from the brain functional overlapping modular organization perspective, which could provide new insight into the adult lifespan changes in brain function and the influence of such changes on cognitive performance.

Variations of Resting-State EEG-Based Functional Networks in Brain Maturation From Early Childhood to Adolescence.

Background and PurposeAlterations in human brain functional networks with maturation have been explored extensively in numerous electroencephalography (EEG) and functional magnetic resonance imaging studies. It is known that the age-related changes in the functional networks occurring prior to adulthood deviate from ordinary trajectories of network-based brain maturation across the adult lifespan.MethodsThis study investigated the longitudinal evolution of resting-state EEG-based functional networks from early childhood to adolescence among 212 pediatric patients (age 12.2±3.5 years, range 4.4–17.9) in 6 frequency bands using 8 types of functional connectivity measures in the amplitude, frequency, and phase domains.ResultsElectrophysiological aspects of network-based pediatric brain maturation were characterized by increases in both functional segregation and integration up to middle adolescence. EEG oscillations in the upper alpha band reflected the age-related increases in mean node strengths and mean clustering coefficients and a decrease in the characteristic path lengths better than did those in the other frequency bands, especially for the phase-domain functional connectivity. The frequency-band-specific age-related changes in the global network metrics were influenced more by volume-conduction effects than by the domain specificity of the functional connectivity measures.ConclusionsWe believe that this is the first study to reveal EEG-based functional network properties during preadult brain maturation based on various functional connectivity measures. The findings potentially have clinical applications in the diagnosis and treatment of age-related brain disorders.

Age- and Sex-Related Topological Organization of Human Brain Functional Networks and Their Relationship to Cognition.

Age and sex associated with changes in the functional brain network topology and cognition in large population of older adults have been poorly understood. We explored this question further by examining differences in 11 resting-state graph theory measures with respect to age, sex, and their relationships with cognitive performance in 17,127 United Kingdom Biobank participants (mean = 62.83 ± 7.41 years). Age was associated with an overall decrease in the effectiveness of network communication (i.e., integration) and loss of functional specialization (i.e., segregation) of specific brain regions. Sex differences were also observed, with women showing more efficient networks, which were less segregated than in men (FDR adjusted p < 0.05). The age-related changes were also more apparent in men than in women, which suggests that men may be more vulnerable to cognitive decline with age. Interestingly, while network segregation and strength of limbic network were only nominally associated with cognitive performance, the network measures collectively were significantly associated with cognition (FDR adjusted p ≤ 0.002). This may imply that individual measures may be inadequate to capture much of the variance in the neural activity or its output and need further refinement. The complexity of the organization of the functional brain may be shaped by the age and sex of an individual, which ultimately may influence the cognitive performance of older adults. Age and sex stratification may be used to inform clinical neuroscience research to identify older adults at risk of cognitive dysfunction.

Novel genetic variants associated with brain functional networks in 18,445 adults from the UK Biobank

Here, we investigated the genetics of weighted functional brain network graph theory measures from 18,445 participants of the UK Biobank (44–80 years). The eighteen measures studied showed low heritability (mean h2SNP = 0.12) and were highly genetically correlated. One genome-wide significant locus was associated with strength of somatomotor and limbic networks. These intergenic variants were located near the PAX8 gene on chromosome 2. Gene-based analyses identified five significantly associated genes for five of the network measures, which have been implicated in sleep duration, neuronal differentiation/development, cancer, and susceptibility to neurodegenerative diseases. Further analysis found that somatomotor network strength was phenotypically associated with sleep duration and insomnia. Single nucleotide polymorphism (SNP) and gene level associations with functional network measures were identified, which may help uncover novel biological pathways relevant to human brain functional network integrity and related disorders that affect it.

Probabilistic mapping of human functional brain networks identifies regions of high group consensus

Many recent developments surrounding the functional network organization of the human brain have focused on data that have been averaged across groups of individuals. While such group-level approaches have shed considerable light on the brain's large-scale distributed systems, they conceal individual differences in network organization, which recent work has demonstrated to be common and widespread. This individual variability produces noise in group analyses, which may average together regions that are part of different functional systems across participants, limiting interpretability. However, cost and feasibility constraints may limit the possibility for individual-level mapping within studies. Here our goal was to leverage information about individual-level brain organization to probabilistically map common functional systems and identify locations of high inter-subject consensus for use in group analyses. We probabilistically mapped 14 functional networks in multiple datasets with relatively high amounts of data. All networks show “core” (high-probability) regions, but differ from one another in the extent of their higher-variability components. These patterns replicate well across four datasets with different participants and scanning parameters. We produced a set of high-probability regions of interest (ROIs) from these probabilistic maps; these and the probabilistic maps are made publicly available, together with a tool for querying the network membership probabilities associated with any given cortical location. These quantitative estimates and public tools may allow researchers to apply information about inter-subject consensus to their own fMRI studies, improving inferences about systems and their functional specializations.

Different visual manipulations have similar effects on quasi-static and dynamic balance responses of young and older people.

BackgroundStudies demonstrated that the older adults can be more susceptible to balance instability after acute visual manipulation. There are different manipulation approaches used to investigate the importance of visual inputs on balance, e.g., eyes closed and blackout glasses. However, there is evidence that eyes open versus eyes closed results in a different organization of human brain functional networks. It is, however, unclear how different visual manipulations affect balance, and whether such effects differ between young and elderly persons. Therefore, this study aimed to determine whether different visual manipulation approaches affect quasi-static and dynamic balance responses differently, and to investigate whether balance responses of young and older adults are affected differently by these various visual conditions.MethodsThirty-six healthy participants (20 young and 16 older adults) performed balance tests (quasi-static and unexpected perturbations) under four visual conditions: Eyes Open, Eyes Closed, Blackout Glasses, and Dark Room. Center of pressure (CoP) and muscle activation (EMG) were quantified.ResultsAs expected, visual deprivation resulted in larger CoP excursions and higher muscle activations during balance tests for all participants. Surprisingly, the visual manipulation approach did not influence balance control in either group. Furthermore, quasi-static and dynamic balance control did not differ between young or older adults. The visual system plays an important role in balance control, however, similarly for both young and older adults. Different visual deprivation approaches did not influence balance results, meaning our results are comparable between participants of different ages. Further studies should investigate whether a critical illumination level may elicit different postural responses between young and older adults.

Partial Phase Cohesiveness in Networks of Networks of Kuramoto Oscillators

Partial, instead of complete, synchronization has been widely observed in various networks, including, in particular, brain networks. Motivated by data from human brain functional networks, in this article, we analytically show that partial synchronization can be induced by strong regional connections in coupled subnetworks of Kuramoto oscillators. To quantify the required strength of regional connections, we first obtain a critical value for the algebraic connectivity of the corresponding subnetwork using the incremental two-norm. We then introduce the concept of the <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">generalized complement graph</i> , and obtain another condition on the node strength by using the incremental <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\infty$</tex-math></inline-formula> -norm. Under these two conditions, regions of attraction for partial phase cohesiveness are estimated in the forms of the incremental two- and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\infty$</tex-math></inline-formula> -norms, respectively. Our result based on the incremental <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\infty$</tex-math></inline-formula> -norm is the first known criterion that applies to noncomplete graphs. Numerical simulations are performed on a two-level network to illustrate our theoretical results; more importantly, we use real anatomical brain network data to show how our results may contribute to a better understanding of the interplay between anatomical structure and empirical patterns of synchrony.

Estimation and Clustering in Popularity Adjusted Block Model

AbstractThe paper considers the Popularity Adjusted Block model (PABM) introduced by Sengupta and Chen (Journal of the Royal Statistical Society Series B, 2018, 80, 365–386). We argue that the main appeal of the PABM is the flexibility of the spectral properties of the graph which makes the PABM an attractive choice for modelling networks that appear in biological sciences. We expand the theory of PABM to the case of an arbitrary number of communities which possibly grows with a number of nodes in the network and is not assumed to be known. We produce estimators of the probability matrix and of the community structure and, in addition, provide non-asymptotic upper bounds for the estimation and the clustering errors. We use the Sparse Subspace Clustering (SSC) approach for partitioning the network into communities, the approach that, to the best of our knowledge, has not been used for the clustering network data. The theory is supplemented by a simulation study. In addition, we show advantages of the PABM for modelling a butterfly similarity network and a human brain functional network.

Revisiting Functional Connectivity for Infraslow Scale-Free Brain Dynamics Using Complex Wavelets.

The analysis of human brain functional networks is achieved by computing functional connectivity indices reflecting phase coupling and interactions between remote brain regions. In magneto- and electroencephalography, the most frequently used functional connectivity indices are constructed based on Fourier-based cross-spectral estimation applied to specific fast and band-limited oscillatory regimes. Recently, infraslow arrhythmic fluctuations (below the 1 Hz) were recognized as playing a leading role in spontaneous brain activity. The present work aims to propose to assess functional connectivity from fractal dynamics, thus extending the assessment of functional connectivity to the infraslow arrhythmic or scale-free temporal dynamics of M/EEG-quantified brain activity. Instead of being based on Fourier analysis, new Imaginary Coherence and weighted Phase Lag indices are constructed from complex-wavelet representations. Their performances are first assessed on synthetic data by means of Monte-Carlo simulations, and they are then compared favorably against the classical Fourier-based indices. These new assessments of functional connectivity indices are also applied to MEG data collected on 36 individuals both at rest and during the learning of a visual motion discrimination task. They demonstrate a higher statistical sensitivity, compared to their Fourier counterparts, in capturing significant and relevant functional interactions in the infraslow regime and modulations from rest to task. Notably, the consistent overall increase in functional connectivity assessed from fractal dynamics from rest to task correlated with a change in temporal dynamics as well as with improved performance in task completion, which suggests that the complex-wavelet weighted Phase Lag index is the sole index is able to capture brain plasticity in the infraslow scale-free regime.