Integration Of Brain Networks Research Articles

Morphometric Integration of Brain Networks in Young Children Exposed to Maternal Depression in a South African Birth Cohort

Morphometric Integration of Brain Networks in Young Children Exposed to Maternal Depression in a South African Birth Cohort

Pervasive alterations of intra-axonal volume and network organization in young children with a 16p11.2 deletion

Reciprocal Copy Number Variants (CNVs) at the 16p11.2 locus confer high risk for autism spectrum disorder (ASD) and other neurodevelopmental disorders (NDDs). Morphometric MRI studies have revealed large and pervasive volumetric alterations in carriers of a 16p11.2 deletion. However, the specific neuroanatomical mechanisms underlying such alterations, as well as their developmental trajectory, are still poorly understood. Here we explored differences in microstructural brain connectivity between 24 children carrying a 16p11.2 deletion and 66 typically developing (TD) children between 2 and 8 years of age. We found a large pervasive increase of intra-axonal volume widespread over a high number of white matter tracts. Such microstructural alterations in 16p11.2 deletion children were already present at an early age, and led to significant changes in the global efficiency and integration of brain networks mainly associated to language, motricity and socio-emotional behavior, although the widespread pattern made it unlikely to represent direct functional correlates. Our results shed light on the neuroanatomical basis of the previously reported increase of white matter volume, and align well with analogous evidence of altered axonal diameter and synaptic function in 16p11.2 mice models. We provide evidence of a prevalent mechanistic deviation from typical maturation of brain structural connectivity associated with a specific biological risk to develop ASD. Future work is warranted to determine how this deviation contributes to the emergence of symptoms observed in young children diagnosed with ASD and other NDDs.

Measures of resting-state brain network segregation and integration vary in relation to data quantity: implications for within and between subject comparisons of functional brain network organization.

Measures of functional brain network segregation and integration vary with an individual's age, cognitive ability, and health status. Based on these relationships, these measures are frequently examined to study and quantify large-scale patterns of network organization in both basic and applied research settings. However, there is limited information on the stability and reliability of the network measures as applied to functional time-series; these measurement properties are critical to understand if the measures are to be used for individualized characterization of brain networks. We examine measurement reliability using several human datasets (Midnight Scan Club and Human Connectome Project [both Young Adult and Aging]). These datasets include participants with multiple scanning sessions, and collectively include individuals spanning a broad age range of the adult lifespan. The measurement and reliability of measures of resting-state network segregation and integration vary in relation to data quantity for a given participant's scan session; notably, both properties asymptote when estimated using adequate amounts of clean data. We demonstrate how this source of variability can systematically bias interpretation of differences and changes in brain network organization if appropriate safeguards are not included. These observations have important implications for cross-sectional, longitudinal, and interventional comparisons of functional brain network organization.

Synergistic integration of Multi-View Brain Networks and advanced machine learning techniques for auditory disorders diagnostics

In the field of audiology, achieving accurate discrimination of auditory impairments remains a formidable challenge. Conditions such as deafness and tinnitus exert a substantial impact on patients’ overall quality of life, emphasizing the urgent need for precise and efficient classification methods. This study introduces an innovative approach, utilizing Multi-View Brain Network data acquired from three distinct cohorts: 51 deaf patients, 54 with tinnitus, and 42 normal controls. Electroencephalogram (EEG) recording data were meticulously collected, focusing on 70 electrodes attached to an end-to-end key with 10 regions of interest (ROI). This data is synergistically integrated with machine learning algorithms. To tackle the inherently high-dimensional nature of brain connectivity data, principal component analysis (PCA) is employed for feature reduction, enhancing interpretability. The proposed approach undergoes evaluation using ensemble learning techniques, including Random Forest, Extra Trees, Gradient Boosting, and CatBoost. The performance of the proposed models is scrutinized across a comprehensive set of metrics, encompassing cross-validation accuracy (CVA), precision, recall, F1-score, Kappa, and Matthews correlation coefficient (MCC). The proposed models demonstrate statistical significance and effectively diagnose auditory disorders, contributing to early detection and personalized treatment, thereby enhancing patient outcomes and quality of life. Notably, they exhibit reliability and robustness, characterized by high Kappa and MCC values. This research represents a significant advancement in the intersection of audiology, neuroimaging, and machine learning, with transformative implications for clinical practice and care.

Top-down threat bias in pain perception is predicted by higher segregation between resting-state networks.

Top-down processes such as expectations have a strong influence on pain perception. Predicted threat of impending pain can affect perceived pain even more than the actual intensity of a noxious event. This type of threat bias in pain perception is associated with fear of pain and low pain tolerance, and hence the extent of bias varies between individuals. Large-scale patterns of functional brain connectivity are important for integrating expectations with sensory data. Greater integration is necessary for sensory integration; therefore, here we investigate the association between system segregation and top-down threat bias in healthy individuals. We show that top-down threat bias is predicted by less functional connectivity between resting-state networks. This effect was significant at a wide range of network thresholds and specifically in predefined parcellations of resting-state networks. Greater system segregation in brain networks also predicted higher anxiety and pain catastrophizing. These findings highlight the role of integration in brain networks in mediating threat bias in pain perception.

Spatial Dynamic Subspaces Encode Sex-Specific Schizophrenia Disruptions in Transient Network Overlap and its Links to Genetic Risk

BackgroundSchizophrenia research reveals sex differences in incidence, symptoms, genetic risk factors, and brain function. However, a knowledge gap remains regarding sex-specific schizophrenia alterations in brain function. Schizophrenia is considered a dysconnectivity syndrome, but the dynamic integration and segregation of brain networks are poorly understood. Recent advances in resting-state fMRI allow us to study spatial dynamics, the phenomenon of brain networks spatially evolving over time. Nevertheless, estimating time-resolved networks remains challenging due to low signal-to-noise, limited short-time information, and uncertain network identification. MethodsWe adapt a reference-informed network estimation technique to capture time-resolved networks and their dynamic spatial integration and segregation for 315 controls and 193 schizophrenia individuals. We focus on time-resolved spatial functional network connectivity (spFNC), an estimate of network spatial coupling, to study sex-specific alterations in schizophrenia and their links to genomic data. ResultsOur findings are consistent with the dysconnectivity and neurodevelopment hypotheses and align with the cerebello-thalamo-cortical, triple-network, and frontoparietal dysconnectivity models, helping to unify them. The potential unification offers a new understanding of the underlying mechanisms. Notably, the posterior default mode/salience spFNC exhibits sex-specific schizophrenia alteration during the state with the highest global network integration and correlates with schizophrenia genetic risk. This dysfunction is reflected in regions with weak functional connectivity to corresponding networks. ConclusionsOur method can effectively capture spatially dynamic networks, detect nuanced schizophrenia effects including sex-specific ones, and reveal the intricate relationship of dynamic information to genomic data. The results also underscore the clinical potential of dynamic spatial dependence and weak connectivity.

Effective Connectivity Changes among Brain Hierarchical Architecture of Pre-Supplementary Motor Area in Taxi Drivers

Much effort has been devoted towards the identification of brain areas recruited during driving—as one of the most common motor skills of human beings. However, how driving experience impacts on the brain’s intrinsic functional architecture has not been fully investigated. Using resting-state fMRI data collected from 20 taxi drivers and 20 nondrivers, this paper asks whether there exists specific brain network integration encoding driving behavior. First, to address this, we proposed a general framework combining whole-brain functional connectivity analysis with effective connectivity analysis based on spectral Dynamic Causal Modeling. The validation results indicated that the application of this framework could effectively discover the brain network that best explained the observed BOLD fluctuations. Second, by segmenting supplementary motor area (SMA) into pre-SMA and SMA proper sub-regions, we used the above framework and discovered a hierarchical architecture with pre-SMA located at the higher level in both driver and control groups. Third, we further evaluated the possibility that driving behavior could be encoded by directed connections among the hierarchy, and found that the effective connectivity from pre-SMA to left superior frontal gyrus could distinguish drivers from nondrivers with a sensitivity of 80%. Our findings provide a new paradigm for analyzing the brain’s intrinsic functional integration, and may shed new light on the theory of neuroplasticity that training and experience can remodel the patterns of correlated spontaneous brain activity between specific processing regions. Meanwhile, from a methodological advantage perspective, our proposed framework takes the functional connectivity results as a prior, enabling subsequent spectral DCM to efficiently assess functional integration at a whole-brain scale, which is not available by only using other DCM methods, such as stochastic DCM or the State-of-the-Art multimodal DCM.

Brain network integration underpins differential susceptibility of adolescent anxiety - ERRATUM.

Brain network integration underpins differential susceptibility of adolescent anxiety - ERRATUM.

Brain network integration underpins differential susceptibility of adolescent anxiety.

Parenting is a common and potent environmental factor influencing adolescent anxiety. Yet, the underlying neurobiological susceptibility signatures remain elusive. Here, we used a longitudinal twin neuroimaging study to investigate the brain network integration and its heritable relation to underpin the neural differential susceptibility of adolescent anxiety to parenting environments. 216 twins from the Beijing Twin Study completed the parenting and anxiety assessments and fMRI scanning. We first identified the brain network integration involved in the influences of parenting at age 12 on anxiety symptoms at age 15. We then estimated to what extent heritable sensitive factors are responsible for the susceptibility of brain network integration. Consistent with the differential susceptibility theory, the results showed that hypo-connectivity within the central executive network amplified the impact of maternal hostility on anxiety symptoms. A high anti-correlation between the anterior salience and default mode networks played a similar modulatory role in the susceptibility of adolescent anxiety to paternal hostility. Genetic influences (21.18%) were observed for the connectivity pattern in the central executive network. Brain network integration served as a promising neurobiological signature of the differential susceptibility to adolescent anxiety. Our findings deepen the understanding of the neural sensitivity in the developing brain and can inform early identification and personalized interventions for adolescents at risk of anxiety disorders.

Associations of resilience, white matter topological organization, and cognitive functions in first-episode, drug-naïve schizophrenia patients: A moderated mediation analysis

BackgroundCognitive deficits are core symptoms of schizophrenia (SZ) and are associated with impaired resilience to stress. Different cognitive functions appeared to be interrelated, and the mechanism may involve neural alterations. The disrupted topological organization indicated abnormalities in the segregation and integration of brain networks that support various cognitive processes in SZ patients. Therefore, this study aimed to assess the direct and indirect effects of resilience on cognitive functions. We hypothesized that topological properties would moderate these associations. MethodsForty-nine SZ patients and fifty-two healthy controls (HCs) were recruited in this study. The Connor-Davidson Resilience Scale and the MATRICS Consensus Cognitive Battery were used to examine resilience and cognitive functions, respectively, and a graph theory approach was used to assess white matter topological organization. ResultsCompared to HCs, SZ patients showed lower levels of resilience and cognitive functions in multiple domains as well as abnormal global properties and nodal metrics. In addition, shorter characteristic path length was associated with a stronger indirect effect of resilience on working memory through processing speed in SZ patients. ConclusionCharacteristic path length might moderate the mediating effects of processing speed in the relationship between resilience and working memory in schizophrenia patients.

Differences in Brain Functional Network Topology in High and Low Working Memory Performance

Nowadays the network approach in neuroscience provides a promising way of analyzing neurophysiological mechanisms that underlie psychological functions and is widely used to study working memory. To date, data obtained in neuroimaging studies links working memory with topological features of brain networks, such as increased connectivity between frontal, parietal, and temporal regions, as well as increased integration in brain networks as a whole. The present study examines the relationship between the topological characteristics of functional brain networks with the performance in the Sternberg item recognition paradigm based on electroencephalographic data. It is shown that the higher performance in Sternberg paradigm, implying a higher efficiency of the processes of encoding, storage, and retrieval of information from working memory, is associated with an increase in the integration of functional networks, expressed in differences in the clustering coefficient, participation coefficient, Wiener index and eigenvector centrality between the groups of high and low working memory task performance (p < .01). In addition, our data suggest the variability in the topological pattern of connectivity, which can be traced through changes in the magnitude of the standard deviation of the values of topological metrics during the task.

Altered Brain Connectivity and Network Topological Organization in a Non-ordinary State of Consciousness Induced by Hypnosis.

Hypnosis has been shown to be of clinical utility; however, its underlying neural mechanisms remain unclear. This study aims to investigate altered brain dynamics during the non-ordinary state of consciousness induced by hypnosis. We studied high-density EEG in 9 healthy participants during eyes-closed wakefulness and during hypnosis, induced by a muscle relaxation and eyes fixation procedure. Using hypotheses based on internal and external awareness brain networks, we assessed region-wise brain connectivity between six ROIs (right and left frontal, right and left parietal, upper and lower midline regions) at the scalp level and compared across conditions. Data-driven, graph-theory analyses were also carried out to characterize brain network topology in terms of brain network segregation and integration. During hypnosis, we observed (1) increased delta connectivity between left and right frontal, as well as between right frontal and parietal regions; (2) decreased connectivity for alpha (between right frontal and parietal and between upper and lower midline regions) and beta-2 bands (between upper midline and right frontal, frontal and parietal, also between upper and lower midline regions); and (3) increased network segregation (short-range connections) in delta and alpha bands, and increased integration (long-range connections) in beta-2 band. This higher network integration and segregation was measured bilaterally in frontal and right parietal electrodes, which were identified as central hub regions during hypnosis. This modified connectivity and increased network integration-segregation properties suggest a modification of the internal and external awareness brain networks that may reflect efficient cognitive-processing and lower incidences of mind-wandering during hypnosis.

Neural pathways of attitudes toward foreign languages predict academic performance.

Learning attitude is thought to impact students' academic achievement and success, but the underlying neurocognitive mechanisms of learning attitudes remain unclear. The purpose of the present study was to investigate the neural markers linked to attitudes toward foreign languages and how they contribute to foreign-language performance. Forty-one Chinese speakers who hold differentiated foreign language (English) attitudes were asked to complete an English semantic judgment task during a functional magnetic resonance imaging (fMRI) experiment. Multimethod brain imaging analyses showed that, compared with the positive attitude group (PAG), the negative attitude group (NAG) showed increased brain activation in the left STG and functional connectivity between the left STG and the right precentral gyrus (PCG), as well as changed functional segregation and integration of brain networks under the English reading task, after controlling for English reading scores. Mediation analysis further revealed that left STG activity and STG-PCG connectivity mediated the relationships between English attitudes and English reading performance. Taken together, these findings suggest that objective neural markers related to subjective foreign language attitudes (FLAs) exist and that attitude-related neural pathways play important roles in determining students' academic performance. Our findings provide new insights into the neurobiological mechanisms by which attitudes regulate academic performance.

Functional brain network features specify DBS outcome for patients with treatment resistant depression.

Deep brain stimulation (DBS) has shown therapeutic benefits for treatment resistant depression (TRD). Stimulation of the subcallosal cingulate gyrus (SCG) aims to alter dysregulation between subcortical and cortex. However, the 50% response rates for SCG-DBS indicates that selection of appropriate patients is challenging. Since stimulation influences large-scale network function, we hypothesized that network features can be used as biomarkers to inform outcome. In this pilot project, we used resting-state EEG recorded longitudinally from 10 TRD patients with SCG-DBS (11 at baseline). EEGs were recorded before DBS-surgery, 1-3 months, and 6 months post surgery. We used graph theoretical analysis to calculate clustering coefficient, global efficiency, eigenvector centrality, energy, and entropy of source-localized EEG networks to determine their topological/dynamical features. Patients were classified as responders based on achieving a 50% or greater reduction in Hamilton Depression (HAM-D) scores from baseline to 12 months post surgery. In the delta band, false discovery rate analysis revealed that global brain network features (segregation, integration, synchronization, and complexity) were significantly lower and centrality of subgenual anterior cingulate cortex (ACC) was higher in responders than in non-responders. Accordingly, longitudinal analysis showed SCG-DBS increased global network features and decreased centrality of subgenual ACC. Similarly, a clustering method separated two groups by network features and significant correlations were identified longitudinally between network changes and depression symptoms. Despite recent speculation that certain subtypes of TRD are more likely to respond to DBS, in the SCG it seems that underlying brain network features are associated with ability to respond to DBS. SCG-DBS increased segregation, integration, and synchronizability of brain networks, suggesting that information processing became faster and more efficient, in those patients in whom it was lower at baseline. Centrality results suggest these changes may occur via altered connectivity in specific brain regions especially ACC. We highlight potential mechanisms of therapeutic effect for SCG-DBS.

Altered dynamic functional network connectivity and topological organization variance in patients with white matter hyperintensities.

White matter hyperintensities (WMHs) of presumed vascular origin are important imaging biomarkers of cerebral small vessel disease (CSVD). Previous studies have verified abnormal functional brain networks in CSVD. However, most of these studies rely on static functional connectivity, and only a few focus on the varying severity of the WMHs. Hence, our study primarily explored the disrupted dynamic functional network connectivity (dFNC) and topological organization variance in patients with WMHs. This study included 38 patients with moderate WMHs, 47 with severe WMHs, and 68 healthy controls (HCs). Ten independent components were chosen using independent component analysis based on resting-state functional magnetic resonance imaging. The dFNC of each participant was estimated using sliding windows and k-means clustering. We identified three reproducible dFNC states. Among them, patients with WMHs had a significantly higher occurrence in the sparsely connected State 1, but a lower occurrence and shorter duration in the positive and stronger connected State 3. Regarding topological organization variance, patients with WMHs showed higher variance in local efficiency but not global efficiency compared to HCs. Among the WMH subgroups, patients with severe WMHs showed similar but more obvious alterations than those with moderate WMHs. These altered network characteristics indicated an imbalance between the functional segregation and integration of brain networks, which was correlated with global cognition, memory, executive functions, and visuospatial abilities. Our study confirmed aberrant dFNC state metrics and topological organization variance in patients with moderate-to-severe WMHs; thus, it might provide a new pathway for exploring the pathogenesis of cognitive impairment.

The Cerebellum’s Orchestra: Understanding the Functional Connectivity of Its Lobes and Deep Nuclei in Coordination and Integration of Brain Networks

The cerebellum, a crucial brain region, significantly contributes to various brain functions. Although it occupies a small portion of the brain, it houses nearly half of the neurons in the nervous system. Previously thought to be solely involved in motor activities, the cerebellum has since been found to play a role in cognitive, sensory, and associative functions. To further elucidate the intricate neurophysiological characteristics of the cerebellum, we investigated the functional connectivity of cerebellar lobules and deep nuclei with 8 major functional brain networks in 198 healthy subjects. Our findings revealed both similarities and differences in the functional connectivity of key cerebellar lobules and nuclei. Despite robust functional connectivity among these lobules, our results demonstrated that they exhibit heterogeneous functional integration with different functional networks. For instance, lobules 4, 5, 6, and 8 were linked to sensorimotor networks, while lobules 1, 2, and 7 were associated with higher-order, non-motor, and complex functional networks. Notably, our study uncovered a lack of functional connectivity in lobule 3, strong connections between lobules 4 and 5 with the default mode networks, and connections between lobules 6 and 8 with the salience, dorsal attention, and visual networks. Additionally, we found that cerebellar nuclei, particularly the dentate cerebellar nuclei, were connected to sensorimotor, salience, language, and default-mode networks. This study provides valuable insights into the diverse functional roles of the cerebellum in cognitive processing.

Opposite effects of positive and negative symptoms on resting-state brain networks in schizophrenia

Schizophrenia is a severe psychotic disorder characterized by positive and negative symptoms, but their neural bases remain poorly understood. Here, we utilized a nested-spectral partition (NSP) approach to detect hierarchical modules in resting-state brain functional networks in schizophrenia patients and healthy controls, and we studied dynamic transitions of segregation and integration as well as their relationships with clinical symptoms. Schizophrenia brains showed a more stable integrating process and a more variable segregating process, thus maintaining higher segregation, especially in the limbic system. Hallucinations were associated with higher integration in attention systems, and avolition was related to a more variable segregating process in default-mode network (DMN) and control systems. In a machine-learning model, NSP-based features outperformed graph measures at predicting positive and negative symptoms. Multivariate analysis confirmed that positive and negative symptoms had opposite effects on dynamic segregation and integration of brain networks. Gene ontology analysis revealed that the effect of negative symptoms was related to autistic, aggressive and violent behavior; the effect of positive symptoms was associated with hyperammonemia and acidosis; and the interaction effect was correlated with abnormal motor function. Our findings could contribute to the development of more accurate diagnostic criteria for positive and negative symptoms in schizophrenia.

Brain network integration, segregation and quasi‐periodic activation and deactivation during tasks and rest

Previous studies have shown that a re-organization of the brain's functional connectome expressed in terms of network integration and segregation may play a pivotal role for brain function. However, it has been proven difficult to fully capture both processes independently in a single methodological framework. In this study, by starting from pair-wise assessments of instantaneous phase synchronization and community membership, we assemble spatiotemporally flexible networks that reflect changes in integration/segregation that occur at a spectrum of spatial as well as temporal scales. This is achieved by iteratively assembling smaller networks into larger units under the constraint that the smaller units should be internally integrated, i.e. belong to the same community. The assembled subnetworks can be partly overlapping and differ in size across time. Our results show that subnetwork integration and segregation occur simultaneously in the brain. During task performance, global changes in synchronization between networks arise that are tied to the underlying temporal design of the experiment. We show that a hallmark property of the dynamics of the brain's functional connectome is a presence of quasi-periodic patterns of network activation and deactivation, which during task performance becomes intertwined with the underlying temporal structure of the experimental paradigm. Additionally, we show that the degree of network integration throughout a n-back working memory task is correlated to performance.

Individual differences in harm-related moral values are associated with functional integration of large-scale brain networks of emotional regulation.

Emotions affects moral judgements, and controlled cognitive processes regulate those emotional responses during moral decision making. However, the neurobiological basis of this interaction is unclear. We used a graph theory measurement called participation coefficient ('PC') to quantify the resting-state functional connectivity within and between four meta-analytic groupings (MAGs) associated with emotion generation and regulation, to test whether that measurement predicts individual differences in moral foundations-based values. We found that the PC of one of the MAGs (MAG2) was positively correlated with one of the five recognized moral foundations-the one based on harm avoidance. We also found that increased inter-module connectivity between the ventromedial prefrontal cortex, dorsolateral prefrontal cortex and middle temporal gyrus with other nodes in the four MAGs was likewise associated with higher endorsement of the Harm foundation. These results suggest that individuals' sensitivity to harm is associated with functional integration of large-scale brain networks of emotional regulation. These findings add to our knowledge of how individual variations in our moral values could be reflected by intrinsic brain network organization and deepen our understanding of the relationship between emotion and cognition during evaluations of moral values.

Recovery of Brain Network Integration and Segregation During the Loss and Recovery of Consciousness Induced by Sevoflurane.

Anesthetic-induced loss of consciousness (LOC) has been studied using functional connectivity (FC) and functional network analysis (FNA), manifested as fragmentation of the whole-brain functional network. However, how the fragmented brain networks reversibly recover during the recovery of consciousness (ROC) remains vague. This study aims to investigate the changes in brain network structure during ROC, to better understand the network fragmentation during anesthesia, thus providing insights into consciousness monitoring. We analyzed EEG data recorded from 15 individuals anesthetized by sevoflurane. By investigating the properties of functional networks generated using different brain atlases and performing community detection for functional networks, we explored the changes in brain network structure to understand how fragmented brain networks recover during the ROC. We observed an overall larger FC magnitude during LOC than in the conscious state. The ROC was accompanied by the increasing binary network efficiency, decreasing FC magnitude, and decreasing community similarity with the functional atlas. Furthermore, we observed a negative correlation between modularity and community number ( [Formula: see text] and , linear regression test), in which modularity increased and community number decreased during ROC. Our results show that a larger FC magnitude reveals excessive synchronization of neuronal activities during LOC. The increasing binary network efficiency, decreasing community number, and decreasing community similarity indicate the recovery of functional network integration. The increasing modularity implies the recovery of functional network segregation during ROC. The results suggest the limitation of FC magnitude and modularity in monitoring anesthetized states and the potential of integrated information theory to evaluate consciousness.