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AIM: Mild cognitive impairment (MCI) includes two distinct subtypes, namely progressive MCI (pMCI) and stable MCI (sMCI). The objective of this study was to identify the topological reorganization of brain functional networks in patients with pMCI and sMCI. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was applied to patients with pMCI, sMCI and healthy controls. Graph theory was applied to study the topological characteristics of the brain's functional networks, examining global and nodal metrics, modularity, and rich-club organization. Analysis of covariance and two sample t-tests were applied to assess differences in topological attributes between patient groups, alongside correlation analysis, which examined the value of changing topological attributes in predicting various clinical outcomes. Results: Significant differences between each group with regard to network metrics were observed. These included clustering coefficients and small-worldness. At the nodal level, several nodes with an abnormal degree centrality and nodal efficiency were detected. In rich club, pMCI and sMCI patients showed declined connectivity compared with HC. Significant differences were observed in the intra- and inter-module connections among the three groups. Particularly noteworthy was the irreplaceable role of the cerebellar module in network interactions. Conclusion: Our study revealed significant differences in network topological properties among sMCI, pMCI and HC patients, which were significantly correlated with cognitive function. Most notably, the cerebellar module played a crucial role in the overall network interactions. In conclusion, these findings could aid in the development of imaging markers used to expedite diagnosis and intervention prior to Alzheimer's disease onset. [ABSTRACT FROM AUTHOR]

Background: Studies on potential disruptions in rich club structure in nursing staff with occupational burnout are lacking. Moreover, existing studies on nurses with burnout are limited by their cross‐sectional design. Purpose: To investigate rich club reorganization in nursing staff before and after the onset of burnout and the underlying impact of anatomical distance on such reconfiguration. Study Type: Prospective, longitudinal. Population: Thirty‐nine hospital nurses (23.67±1.03 years old at baseline, 24.67±1.03 years old at a follow‐up within 1.5 years, 38 female). Field Strength/Sequence: Magnetization‐prepared rapid gradient‐echo and gradient‐echo echo‐planar imaging sequences at 3.0 T. Assessment: The Maslach Burnout Inventory and Symptom Check‐List 90 testing were acquired at each MRI scan. Rich club structure was assessed at baseline and follow‐up to determine whether longitudinal changes were related to burnout and to changes in connectivities with different anatomical distances (short‐, mid‐, and long range). Statistical Tests: Chi‐square, paired‐samples t, two‐sample t, Mann–Whitney U tests, network‐based statistic, Spearman correlation analysis, and partial least squares regression analysis. Significance level: Bonferroni‐corrected P<0.05. Results: In nurses who developed burnout: 1) Strengths of rich club, feeder, local, short‐, mid‐, and long‐range connectivities were significantly decreased at follow‐up compared with baseline. 2) At follow‐up, strengths of above connectivities and that between A5m.R and dlPu.L were significantly correlated with emotional exhaustion (r ranges from −0.57 to −0.73) and anxiety scores (r = −0.56), respectively. 3) Longitudinal change (follow‐up minus baseline) in connectivity strength between A5m.R and dlPu.L reflected change in emotional exhaustion score (r = 0.87). Longitudinal changes in strength of connectivities mainly involving parietal lobe were significantly decreased in nurses who developed burnout compared with those who did not. Data Conclusion: In nurses after the onset of burnout, rich club reorganization corresponded to significant reductions in strength of connectivities with different anatomical distances. Level of Evidence: 1 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by significant cerebral dysfunction, including increased amyloid deposition, gray matter atrophy, and changes in brain function. The involvement of highly connected network hubs, known as the "rich club," in the pathology of the disease remains inconclusive despite previous research efforts. In this study, we aimed to systematically assess the link between the rich club and AD using a multimodal neuroimaging approach. We employed network analyses of diffusion magnetic resonance imaging (MRI), longitudinal assessments of gray matter atrophy, amyloid deposition measurements using positron emission tomography (PET) imaging, and meta‐analytic data on functional activation differences. Our study focused on evaluating the role of both the structural brain network's core and extended rich club regions in individuals with mild cognitive impairment (MCI) and those diagnosed with AD. Our findings revealed that structural rich club regions exhibited accelerated gray matter atrophy and increased amyloid deposition in both MCI and AD. Importantly, these regions remained unaffected by altered functional activation patterns observed outside the core rich club regions. These results shed light on the connection between two major AD biomarkers and the rich club, providing valuable insights into AD as a potential disconnection syndrome. [ABSTRACT FROM AUTHOR]

AIMMild cognitive impairment (MCI) includes two distinct subtypes, namely progressive MCI (pMCI) and stable MCI (sMCI). The objective of this study was to identify the topological reorganization of brain functional networks in patients with pMCI and sMCI.MethodsResting-state functional magnetic resonance imaging (rs-fMRI) was applied to patients with pMCI, sMCI and healthy controls. Graph theory was applied to study the topological characteristics of the brain’s functional networks, examining global and nodal metrics, modularity, and rich-club organization. Analysis of covariance and two sample t-tests were applied to assess differences in topological attributes between patient groups, alongside correlation analysis, which examined the value of changing topological attributes in predicting various clinical outcomes.ResultsSignificant differences between each group with regard to network metrics were observed. These included clustering coefficients and small-worldness. At the nodal level, several nodes with an abnormal degree centrality and nodal efficiency were detected. In rich club, pMCI and sMCI patients showed declined connectivity compared with HC. Significant differences were observed in the intra- and inter-module connections among the three groups. Particularly noteworthy was the irreplaceable role of the cerebellar module in network interactions.ConclusionOur study revealed significant differences in network topological properties among sMCI, pMCI and HC patients, which were significantly correlated with cognitive function. Most notably, the cerebellar module played a crucial role in the overall network interactions. In conclusion, these findings could aid in the development of imaging markers used to expedite diagnosis and intervention prior to Alzheimer’s disease onset.

The brain's structural network follows a hierarchy that is described as rich club (RC) organization, with RC hubs forming the well‐interconnected top of this hierarchy. In this study, we tested whether RC hubs are involved in the processing of hierarchically higher structures in stimulus sequences. Moreover, we explored the role of previously suggested cortical gradients along anterior‐posterior and medial‐lateral axes throughout the frontal cortex. To this end, we conducted a functional magnetic resonance imaging (fMRI) experiment and presented participants with blocks of digit sequences that were structured on different hierarchically nested levels. We additionally collected diffusion weighted imaging data of the same subjects to identify RC hubs. This classification then served as the basis for a region of interest analysis of the fMRI data. Moreover, we determined structural network centrality measures in areas that were found as activation clusters in the whole‐brain fMRI analysis. Our findings support the previously found anterior and medial shift for processing hierarchically higher structures of stimuli. Additionally, we found that the processing of hierarchically higher structures of the stimulus structure engages RC hubs more than for lower levels. Areas involved in the functional processing of hierarchically higher structures were also more likely to be part of the structural RC and were furthermore more central to the structural network. In summary, our results highlight the potential role of the structural RC organization in shaping the cortical processing hierarchy. [ABSTRACT FROM AUTHOR]

Introduction: It has been suggested that the rich club organization in major depressive disorder (MDD) was altered. However, it remained unclear whether the rich club organization could be served as a biomarker that predicted the improvement of clinical symptoms in MDD. Methods: The current study included 29 mild or moderate patients with MDD, who were grouped into a treatment group (receiving cognitive behavioral therapy or real‐time fMRI feedback treatment) and a no‐treatment group. Resting‐state MRI scans were obtained for all participants. Graph theory was employed to investigate the treatment‐related changes in network properties and rich club organization. Results: We found that patients in the treatment group had decreased depressive symptom scores and enhanced rich club connectivity following the nonpharmacological treatment. Moreover, the changes in rich club connectivity were significantly correlated with the changes in depressive symptom scores. In addition, the nonpharmacological treatment on patients with MDD increased functional connectivity mainly among the salience network, default mode network, frontoparietal network, and subcortical network. Patients in the no‐treatment group did not show significant changes in depressive symptom scores and rich club organization. Conclusions: Those results suggested that the remission of depressive symptoms after nonpharmacological treatment in MDD patients was associated with the increased efficiency of global information processing. [ABSTRACT FROM AUTHOR]

Studies of brain network organisation have swiftly adopted graph theory-based quantitative analysis of complicated networks. Small-world topology, densely connected hubs, and modularity characterise the brain's structural and functional systems. Many measures quantify graph topology. It has not yet been determined which measurements are most appropriate for brain network analysis. This work introduces a new parameter applicable to brain network analysis. This parameter may help in the identification of symmetry and the study of symmetry breakdown in the brain. This is important because decreased symmetry in the brain is associated with a decreased chance of developing neurodevelopmental and psychiatric disorders. This work is to study brain networks using maximal independent set-based topological indices. These indices seem to depict significant properties of brain networks, such as clustering, small-worldness, etc. One new parameter introduced in this paper for brain network analysis depends on Zagreb topological indices and independence degree. This parameter is useful for analyzing clusters, rich clubs, small-worldness, and connectivity in modules. [ABSTRACT FROM AUTHOR]

Internet gaming disorder (IGD) has a great negative impact on teenagers’ study and life. It has been included in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders in 2013. However, the neural mechanism of its effect is yet to be unveiled. In this study, we used resting-state functional magnetic resonance imaging (resting-state fMRI) to explore the differences of rich club structures in the functional brain networks of 30 IGD subjects and 30 age/sex-matched healthy controls. The rich club was found in both IGD subjects and healthy controls, involving important brain regions in default mode, executive control, salience, sensorimotor, auditory and visual networks. IGD subjects had significantly higher rich club connection and higher degree in the right pars orbitalis of inferior frontal gyrus than healthy controls. These findings might suggest that IGD might be more correlated with damage to the rich club connection.

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich‐club) brain regions on functional outcome post‐stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3‐months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI‐GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas‐defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non‐rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non‐rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex‐specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female‐specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club‐combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long‐term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women. [ABSTRACT FROM AUTHOR]

Many organizational principles of structural brain networks are established before birth and undergo considerable developmental changes afterwards. These include the topologically central hub regions and a densely connected rich club. While several studies have mapped developmental trajectories of brain connectivity and brain network organization across childhood and adolescence, comparatively little is known about subsequent development over the course of the lifespan. Here, we present a cross‐sectional analysis of structural brain network development in N = 8066 participants aged 5–80 years. Across all brain regions, structural connectivity strength followed an "inverted‐U"‐shaped trajectory with vertex in the early 30s. Connectivity strength of hub regions showed a similar trajectory and the identity of hub regions remained stable across all age groups. While connectivity strength declined with advancing age, the organization of hub regions into a rich club did not only remain intact but became more pronounced, presumingly through a selected sparing of relevant connections from age‐related connectivity loss. The stability of rich club organization in the face of overall age‐related decline is consistent with a "first come, last served" model of neurodevelopment, where the first principles to develop are the last to decline with age. Rich club organization has been shown to be highly beneficial for communicability and higher cognition. A resilient rich club might thus be protective of a functional loss in late adulthood and represent a neural reserve to sustain cognitive functioning in the aging brain. [ABSTRACT FROM AUTHOR]

Objective: The diagnosis of Parkinson's disease (PD) remains challenging. Although 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has revealed the metabolic abnormalities associated with PD at systemic levels, the underlying rich-club organization of the metabolic connectome in these patients remains largely unknown. Materials and Methods: The data of 49 PD patients and 49 well-matched healthy controls (HCs) were retrieved and assessed. An individual metabolic connectome based on the standard uptake value (SUV) was built using the Jensen-Shannon Divergence Similarity Estimation (JSSE) method to compare the rich-club properties between PD patients and HC. Results: Our results showed the rich-club organization of metabolic networks (normalized rich-club coefficients > 1) in the PD and HC group were within a range of thresholds. Further, patients with PD demonstrated lower strength and degree in rich-club connections compared with HCs (strength: HCs = 55.70 8.52, PDs = 52.03 10.49, p = 0.028; degree: HCs = 56.55 8.60, PDs = 52.85 10.62, p = 0.029), but difference between their feeder and local connections was not significant. Conclusion: Individual metabolic networks combined with rich club analysis indicated that PD patients had decreased rich club connections but similar feeder and local connections compared with HCs, indicating rich club connections as a promising marker for early diagnosis of PD. [ABSTRACT FROM AUTHOR]

Objective: Even with successful combination antiretroviral therapy (cART), patients with human immunodeficiency virus positive (HIV+) continue to present structural alterations and neuropsychological impairments. The purpose of this study is to investigate structural brain connectivity alterations and identify the hub regions in HIV+ patients with fully suppressed plasma viral loads. Methods: In this study, we compared the brain structural connectivity in 48 patients with HIV+ treated with a combination of antiretroviral therapy and 48 healthy controls, using diffusion tensor imaging. Further comparisons were made in 24 patients with asymptomatic neurocognitive impairment (ANI) and 24 individuals with non-HIV-associated neurocognitive disorders forming a subset of HIV+ patients. The graph theory model was used to establish the topological metrics. Rich-club analysis was used to identify hub nodes across groups and abnormal rich-club connections. Correlations of connectivity metrics with cognitive performance and clinical variables were investigated as well. Results: At the regional level, HIV+ patients demonstrated lower degree centrality (DC), betweenness centrality (BC), and nodal efficiency (NE) at the occipital lobe and the limbic cortex; and increased BC and nodal cluster coefficient (NCC) in the occipital lobe, the frontal lobe, the insula, and the thalamus. The ANI group demonstrated a significant reduction in the DC, NCC, and NE in widespread brain regions encompassing the occipital lobe, the frontal lobe, the temporal pole, and the limbic system. These results did not survive the Bonferroni correction. HIV+ patients and the ANI group had similar hub nodes that were mainly located in the occipital lobe and subcortical regions. The abnormal connections were mainly located in the occipital lobe in the HIV+ group and in the parietal lobe in the ANI group. The BC in the calcarine fissure was positively correlated with complex motor skills. The disease course was negatively correlated with NE in the middle occipital gyrus. Conclusion: The results suggest that the occipital lobe and the subcortical regions may be important in structural connectivity alterations and cognitive impairment. Rich-club analysis may contribute to our understanding of the neuropathology of HIV-associated neurocognitive disorders. [ABSTRACT FROM AUTHOR]

ObjectiveEven with successful combination antiretroviral therapy (cART), patients with human immunodeficiency virus positive (HIV+) continue to present structural alterations and neuropsychological impairments. The purpose of this study is to investigate structural brain connectivity alterations and identify the hub regions in HIV+ patients with fully suppressed plasma viral loads.MethodsIn this study, we compared the brain structural connectivity in 48 patients with HIV+ treated with a combination of antiretroviral therapy and 48 healthy controls, using diffusion tensor imaging. Further comparisons were made in 24 patients with asymptomatic neurocognitive impairment (ANI) and 24 individuals with non-HIV-associated neurocognitive disorders forming a subset of HIV+ patients. The graph theory model was used to establish the topological metrics. Rich-club analysis was used to identify hub nodes across groups and abnormal rich-club connections. Correlations of connectivity metrics with cognitive performance and clinical variables were investigated as well.ResultsAt the regional level, HIV+ patients demonstrated lower degree centrality (DC), betweenness centrality (BC), and nodal efficiency (NE) at the occipital lobe and the limbic cortex; and increased BC and nodal cluster coefficient (NCC) in the occipital lobe, the frontal lobe, the insula, and the thalamus. The ANI group demonstrated a significant reduction in the DC, NCC, and NE in widespread brain regions encompassing the occipital lobe, the frontal lobe, the temporal pole, and the limbic system. These results did not survive the Bonferroni correction. HIV+ patients and the ANI group had similar hub nodes that were mainly located in the occipital lobe and subcortical regions. The abnormal connections were mainly located in the occipital lobe in the HIV+ group and in the parietal lobe in the ANI group. The BC in the calcarine fissure was positively correlated with complex motor skills. The disease course was negatively correlated with NE in the middle occipital gyrus.ConclusionThe results suggest that the occipital lobe and the subcortical regions may be important in structural connectivity alterations and cognitive impairment. Rich-club analysis may contribute to our understanding of the neuropathology of HIV-associated neurocognitive disorders.

The purpose of this study was to reveal the patterns of reorganization of rich club organization in brain functional networks in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). The study found that the rich club node shifts from sensory/somatomotor network to fronto-parietal network in DLB. For AD, the rich club nodes switch between the temporal lobe with obvious structural atrophy and the frontal lobe, parietal lobe and cerebellum with relatively preserved structure and function. In addition, compared with healthy controls, rich club connectivity was enhanced in the DLB and AD groups. The connection strength of DLB patients was related to cognitive assessment. In conclusion, we revealed the different functional reorganization patterns of DLB and AD. The conversion and redistribution of rich club members may play a causal role in disease-specific outcomes. It may be used as a potential biomarker to provide more accurate prevention and treatment strategies.

Found in varied contexts from neurons to ants to fish, binary decision-making is one of the simplest forms of collective computation. In this process, information collected by individuals about an uncertain environment is accumulated to guide behavior at the aggregate scale. We study binary decision-making dynamics in networks responding to inputs with small signal-to-noise ratios, looking for quantitative measures of collectivity that control performance in this task. We find that decision accuracy is directly correlated with the speed of collective dynamics, which is in turn controlled by three factors: the leading eigenvalue of the network adjacency matrix, the corresponding eigenvector's participation ratio, and distance from the corresponding symmetry-breaking bifurcation. A novel approximation of the maximal attainable timescale near such a bifurcation allows us to predict how decision-making performance scales in large networks based solely on their spectral properties. Specifically, we explore the effects of localization caused by the hierarchical assortative structure of a "rich club" topology. This gives insight into the trade-offs involved in the higher-order structure found in living networks performing collective computations. [ABSTRACT FROM AUTHOR]

Diffusion imaging can assess the white matter connections within the brain, revealing how neural pathways break down in Alzheimer's disease (AD). We analyzed 3-Tesla whole-brain diffusion-weighted images from 202 participants scanned by the Alzheimer's Disease Neuroimaging Initiative-50 healthy controls, 110 with mild cognitive impairment (MCI) and 42 AD patients. From whole-brain tractography, we reconstructed structural brain connectivity networks to map connections between cortical regions. We tested whether AD disrupts the "rich club" - a network property where high-degree network nodes are more interconnected than expected by chance. We calculated the rich club properties at a range of degree thresholds, as well as other network topology measures including global degree, clustering coefficient, path length, and efficiency. Network disruptions predominated in the low-degree regions of the connectome in patients, relative to controls. The other metrics also showed alterations, suggesting a distinctive pattern of disruption in AD, less pronounced in MCI, targeting global brain connectivity, and focusing on more remotely connected nodes rather than the central core of the network. AD involves severely reduced structural connectivity; our step-wise rich club coefficients analyze points to disruptions predominantly in the peripheral network components; other modalities of data are needed to know if this indicates impaired communication among non rich club regions. The highly connected core was relatively preserved, offering new evidence on the neural basis of progressive risk for cognitive decline.

Neurodevelopmental benefits of increased gestation have not been fully characterized in terms of network organization. Since brain function can be understood as an integrated network of neural information from distributed brain regions, investigation of the effects of gestational length on network properties is a critical goal of human developmental neuroscience. Using diffusion tensor imaging and fiber tractography, we investigated the effects of gestational length on the small-world attributes and rich club organization of 147 preadolescent children, whose gestational length ranged from 29 to 42 weeks. Higher network efficiency was positively associated with longer gestation. The longer gestation was correlated with increased local efficiency in the posterior medial cortex, including the precuneus, cuneus, and superior parietal regions. Rich club organization was also observed indicating the existence of highly interconnected structural hubs formed in preadolescent children. Connectivity among rich club members and from rich club regions was positively associated with the length of gestation, indicating the higher level of topological benefits of structural connectivity from longer gestation in the predominant regions of brain networks. The findings provide evidence that longer gestation is associated with improved topological organization of the preadolescent brain, characterized by the increased communication capacity of the brain network and enhanced directional strength of brain connectivity with central hub regions.

Principles of network topology have been widely studied in the human connectome. Of particular interest is the modularity of the human brain, where the connectome is divided into subnetworks from which changes with development, aging or disease can be investigated. We present a weighted network measure, the Network Dependency Index (NDI), to identify an individual region’s importance to the global functioning of the network. Importantly, we utilize NDI to differentiate four subnetworks (Tiers) in the human connectome following Gaussian mixture model fitting. We analyze the topological aspects of each subnetwork with respect to age and compare it to rich club-based subnetworks (rich club, feeder, and seeder). Our results first demonstrate the efficacy of NDI to identify more consistent, central nodes of the connectome across age groups, when compared with the rich club framework. Stratifying the connectome by NDI led to consistent subnetworks across the life-span, revealing distinct patterns associated with age where, for example, the key relay nuclei and cortical regions are contained in a subnetwork with highest NDI. The divisions of the human connectome derived from our data-driven NDI framework have the potential to reveal topological alterations described by network measures through the life-span.

The brain network is one specific type of critical infrastructure networks, which supports the cognitive function of biological systems. With the importance of network reliability in system design, evaluation, operation, and maintenance, we use the percolation methods of network reliability on brain networks and study the network resistance to disturbances and relevant failure modes. In this paper, we compare the brain networks of different species, including cat, fly, human, mouse, and macaque. The differences in structural features reflect the requirements for varying levels of functional specialization and integration, which determine the reliability of brain networks. In the percolation process, we apply different forms of disturbances to the brain networks based on metrics that characterize the network structure. Our findings suggest that the brain networks are mostly reliable against random or k-core-based percolation with their structure design, yet becomes vulnerable under betweenness or degree-based percolation. Our results might be useful to identify and distinguish brain connectivity failures that have been shown to be related to brain disorders, as well as the reliability design of other technological networks.

Cushing disease (CD) is a rare clinical disease in which brain structural and function are impaired as the result of excessive cortisol. However, little is known whether rich-club organization changes in patients with CD, as visualized on resting-state magnetic resonance imaging (fMRI), can reverse to normal conditions after transsphenoidal surgery (TSS). In this study, we aimed to investigate whether the functional connectivity of rich-club organization is affected and whether any abnormal changes may reverse after TSS. In this study, 38 patients with active CD, 33 with patients with CD in remission, and 41 age-, sex-, and education-matched healthy control participants underwent resting-state fMRI. Brain functional connectivity was constructed based on fMRI and rich club was calculated with graph theory approach. We constructed the functional brain networks for all participants and calculated rich-club connectivity based on fMRI. We identified left precuneus, right precuneus, left middle cingulum, right middle cingulum, right inferior temporal, right middle temporal, right lingual, right postcentral, right middle occipital, and right precentral regions as rich club nodes. Compared with healthy control participants, rich-club connectivity was significantly lower in patients with active CD (P < 0.001). Moreover, abnormal rich-club connectivity improved to normal after TSS. Our results show rich-club organization was disrupted in patients with active CD with excessive cortisol production. TSS can reverse abnormal rich-club connectivity. Rich club may be a new indicator to investigate the outcomes of TSS and to increase our understanding of the effect of excessive cortisol on brain functional connectivity in patients with CD. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate whether the large-scale structural rich club organization was abnormal in patients with Leber's hereditary optic neuropathy (LHON) using diffusion tensor imaging (DTI), and the associations among disrupted brain structural connectivity, disease duration, and neuro-ophthalmological impairment. Methods: Nineteen acute, 34 chronic LHON patients, and 36 healthy controls (HC) underwent DTI and neuro-ophthalmological measurements. The brain structural network and rich club organization were constructed based on deterministic fiber tracking at the individual level. Then intergroup differences among the acute, chronic LHON patients and healthy controls (HC) in three types of structural connections, including rich club, feeder, and local ones, were compared. Network-based Statistics (NBS) was also used to test the intergroup connectivity differences for each fiber. Several linear and nonlinear curve fit models were applied to explore the associations among large-scale brain structural connectivity, disease duration, and neuro-ophthalmological metrics. Results: Compared to the HC, both the acute and chronic LHON patients had consistently significantly lower fractional anisotropy (FA) and higher radial diffusion (RD) for feeder connections (p 0.05, FDR correction). NBS also identified reduced FA of three feeder connections and five local ones linking visual, auditory, and basal ganglia areas in LHON patients (p 0.05, FDR correction). A significant negative correlation was shown between the retinal nerve fiber layer (RNFL) thickness and disease duration (p

BackgroundSubjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) were considered to be a continuum of Alzheimer’s disease (AD) spectrum. The abnormal topological architecture and rich-club organization in the brain functional network can reveal the pathology of the AD spectrum. However, few studies have explored the disrupted patterns of diverse club organizations and the combination of rich- and diverse-club organizations in SCD and aMCI.MethodsWe collected resting-state functional magnetic resonance imaging data of 19 SCDs, 29 aMCIs, and 28 healthy controls (HCs) from the Alzheimer’s Disease Neuroimaging Initiative. Graph theory analysis was used to analyze the network metrics and rich- and diverse-club organizations simultaneously.ResultsCompared with HC, the aMCI group showed altered small-world and network efficiency, whereas the SCD group remained relatively stable. The aMCI group showed reduced rich-club connectivity compared with the HC. In addition, the aMCI group showed significantly increased feeder connectivity and decreased local connectivity of the diverse club compared with the SCD group. The overlapping nodes of the rich club and diverse club showed a significant difference in nodal efficiency and shortest path length (Lp) between groups. Notably, the Lp values of overlapping nodes in the SCD and aMCI groups were significantly associated with episodic memory.ConclusionThe present study demonstrates that the network properties of SCD and aMCI have varying degrees of damage. The combination of the rich club and the diverse club can provide a novel insight into the pathological mechanism of the AD spectrum. The altered patterns in overlapping nodes might be potential biomarkers in the diagnosis of the AD spectrum.

PurposeInsomnia is the most prevalent sleep complaint in the general population but is often intractable due to uncertainty regarding the underlying pathomechanisms. Sleep is regulated by a network of neural structures interconnected with the core nodes of the brain connectome referred to as the “rich club”. We examined alterations in brain rich-club organization as revealed by diffusion tensor imaging (DTI) and the statistical relationships between abnormalities in rich-club metrics and the clinical features of primary insomnia (PI).MethodsThis study recruited 43 primary insomnia (PI) patients and 42 age-, sex-, and education level-matched healthy controls (HCs). Differences in global and regional network parameters between PI and healthy control groups were compared by nonparametric tests, and Spearman's correlations were calculated to assess associations of these network metrics with PI-related clinical features, including disease duration and scores on the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Self-Rating Anxiety Scale, and Self-Rating Depression Scale.ResultsWeighted white matter networks exhibited weaker rich-club organization in PI patients than HCs across different thresholds (50%, 75%, and 90%) and parcellation schemes [automated anatomical labeling (AAL)-90 and AAL-1024]. Aberrant rich-club organization was found mainly in limbic-cortical-basal ganglia circuits and the default-mode network.ConclusionsAbnormal rich-club metrics are a characteristic feature of PI-related to disease severity. These metrics provide potential clues to PI pathogenesis and may be useful as diagnostic markers and for assessment of treatment response.

Processing speed (PS) impairment is one of the most severe and common cognitive deficits in schizophrenia. Previous studies have reported correlations between PS and white matter diffusion properties, including fractional anisotropy (FA), in several fiber bundles in schizophrenia, suggesting that white matter alterations could underpin decreased PS. In schizophrenia, white matter alterations are most prevalent within inter-hub connections of the rich club. However, the spatial and topological characteristics of this association between PS and FA have not been investigated in patients. In this context, we tested whether structural connections comprising the rich club network would underlie PS impairment in 298 patients with schizophrenia or schizoaffective disorder and 190 healthy controls from the Australian Schizophrenia Research Bank. PS, measured using the digit symbol coding task, was largely (Cohen's d = 1.33) and significantly (P < .001) reduced in the patient group when compared with healthy controls. Significant associations between PS and FA were widespread in the patient group, involving all cerebral lobes. FA was not associated with other cognitive measures of phonological fluency and verbal working memory in patients, suggesting specificity to PS. A topological analysis revealed that despite being spatially widespread, associations between PS and FA were over-represented among connections forming the rich club network. These findings highlight the need to consider brain network topology when investigating high-order cognitive functions that may be spatially distributed among several brain regions. They also reinforce the evidence that brain hubs and their interconnections may be particularly vulnerable parts of the brain in schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) were considered to be a continuum of Alzheimer's disease (AD) spectrum. The abnormal topological architecture and rich-club organization in the brain functional network can reveal the pathology of the AD spectrum. However, few studies have explored the disrupted patterns of diverse club organizations and the combination of rich- and diverse-club organizations in SCD and aMCI. Methods: We collected resting-state functional magnetic resonance imaging data of 19 SCDs, 29 aMCIs, and 28 healthy controls (HCs) from the Alzheimer's Disease Neuroimaging Initiative. Graph theory analysis was used to analyze the network metrics and rich- and diverse-club organizations simultaneously. Results: Compared with HC, the aMCI group showed altered small-world and network efficiency, whereas the SCD group remained relatively stable. The aMCI group showed reduced rich-club connectivity compared with the HC. In addition, the aMCI group showed significantly increased feeder connectivity and decreased local connectivity of the diverse club compared with the SCD group. The overlapping nodes of the rich club and diverse club showed a significant difference in nodal efficiency and shortest path length (L p) between groups. Notably, the L p values of overlapping nodes in the SCD and aMCI groups were significantly associated with episodic memory. Conclusion: The present study demonstrates that the network properties of SCD and aMCI have varying degrees of damage. The combination of the rich club and the diverse club can provide a novel insight into the pathological mechanism of the AD spectrum. The altered patterns in overlapping nodes might be potential biomarkers in the diagnosis of the AD spectrum. [ABSTRACT FROM AUTHOR]

Late-life depression (LLD) and mild cognitive impairment (MCI) are risk factors for Alzheimer disease (AD). However, the interactive effect between LLD and MCI in the progression to AD remains unknown. The purpose of this research is to clarify whether this interaction exists and determined the characteristics of the structural change patterns in LLD and MCI. To address this question, a total 225 participants (91 with intact cognitive function (IC), 34 with MCI, 35 with LLD-IC, 47 with LLD-MCI and 18 with AD) were recruited for the current study and their T1 scanning were acquired. Machine learning was applied to estimate the brain's age gap according to grey matter information (thickness and volume was calculated based on the Human Connectome Project Multi-Modal Parcellation version 1.0 and the Desikan atlas). A structural covariance network (SCN) was constructed based on grey matter volume. Rich-club analysis, global network properties and the Jaccard distance were utilized to describe the topological features in each cohort. Their cognitive functions (executive function, processing speed and memory) were evaluated by a full-scale battery of neuropsychological tests. The interactive effect between LLD and MCI was detected through the brain age gap. The estimated age was positively correlated with processing speed and memory in LLD and non-LLD subjects. In the SCN analysis, the rich-club coefficient and global network properties were disrupted in the MCI group, but remained normal in the LLD-IC, LLD-MCI and AD groups. There was a significant discrepancy in brain structural change patterns between the AD and other cohorts by the Jaccard distance. The application of machine learning reflects that synergies between LLD and MCI could increase the risk of developing AD. According to the SCN, the structural coordination was disrupted in MCI and was kept normal in the other cohorts, while the discrepancies in brain structural change patterns appeared in AD. Overall, the brain age gap could be a potential predictor of AD, and the Jaccard distance has the potential to be a new type of SCN analysis indicator. • Explore the brain age gap by a machine learning method. • Analysis the structural covariance network characteristic. [ABSTRACT FROM AUTHOR]

Conventional brain functional networks are constructed by extracting the entire time series from functional Magnetic Resonance Imaging (fMRI). Yet such a method is easy to ignore the dynamic interaction patterns of brain regions that essentially change across time. In this study, we analyze the functional connectivity characteristics of Rich Club in resting-state brain functional networks, and study the dynamic functional differences of core brain regions at different time periods. First, the time series is extracted from resting-state fMRI to construct a dynamic brain functional network. Then, Rich Clubs of different time periods are determined by the Rich Club coefficients. In particular, the efficiency of each Rich Club is calculated to examine the influences of the Rich Connections, Feeder Connections and Local Connections. Finally, the node degree, clustering coefficient and efficiency for Rich Club nodes are calculated to quantify the dynamic processes of Rich Clubs, and the functional connectivity of Rich Clubs are compared with those of the functional networks constructed by the entire fMRI time series. Experimental results demonstrate that the distribution of Rich Clubs in the dynamic brain functional network is consistent with that from the entire fMRI time series, while the composition and functional connectivity of Rich Club dynamically change across time. Moreover, Rich connection and Local connection in the brain functional networks show a significant correlation with the efficiency of Rich Club, and the local and the global efficiency of Rich Clubs are greater than that of the global network. These results further illustrate the viewpoint that Rich Clubs have significant influence on the functional characteristics of global brain functional networks. [ABSTRACT FROM AUTHOR]

Purpose: Insomnia is the most prevalent sleep complaint in the general population but is often intractable due to uncertainty regarding the underlying pathomechanisms. Sleep is regulated by a network of neural structures interconnected with the core nodes of the brain connectome referred to as the "rich club". We examined alterations in brain rich-club organization as revealed by diffusion tensor imaging (DTI) and the statistical relationships between abnormalities in rich-club metrics and the clinical features of primary insomnia (PI). Methods: This study recruited 43 primary insomnia (PI) patients and 42 age-, sex-, and education level-matched healthy controls (HCs). Differences in global and regional network parameters between PI and healthy control groups were compared by nonparametric tests, and Spearman's correlations were calculated to assess associations of these network metrics with PI-related clinical features, including disease duration and scores on the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Self-Rating Anxiety Scale, and Self-Rating Depression Scale. Results: Weighted white matter networks exhibited weaker rich-club organization in PI patients than HCs across different thresholds (50%, 75%, and 90%) and parcellation schemes [automated anatomical labeling (AAL)-90 and AAL-1024]. Aberrant rich-club organization was found mainly in limbic-cortical-basal ganglia circuits and the default-mode network. Conclusions: Abnormal rich-club metrics are a characteristic feature of PI-related to disease severity. These metrics provide potential clues to PI pathogenesis and may be useful as diagnostic markers and for assessment of treatment response. [ABSTRACT FROM AUTHOR]

Introduction: Human brain was a complex network of interconnected regions. Recent neuroimaging studies had showed that the disruption of brain connectivity was associated with psychological disorders. Abnormal rich club and robustness of brain networks might have a key role in the pathophysiology of psychogenic erectile dysfunction (pED). Methods: Both diffusion and functional magnetic resonance imaging were performed in pED patients and healthy controls (HC). Measures of rich club organization and robustness under targeted attack were explored. Results: Both pED and HC showed structural and functional rich club organization. However, reduced rich club coefficient was found in pED and different regions in the rich club of structural brain network were less than that of functional brain network. Moreover, decreased connectivity density and strength were only found in feeder connections of functional brain network in pED. In addition, pED showed remarkably reduced resilient to targeted attack and the stability of the functional brain network organization showed more vulnerable to targeted attack in pED. Conclusion: Together, our results provided evidence that pED was characterized by a selective disruption of rich club organization and reduced robustness to attack. The abnormal hub regions and connections of functional brain network, less stable organization of structural brain network, and the abnormal psychological factors might lead to the development of erectile dysfunction in pED. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates that a disruption in brain network organization may play an important role in the pathophysiology of schizophrenia. The neuroimaging fingerprint reflecting the pathophysiology of first-episode schizophrenia remains to be identified. Here, we aimed at characterizing the connectome organization of first-episode medication-naïve patients with schizophrenia. A cross-sectional structural and functional neuroimaging study using two independent samples (principal dataset including 42 medication-naïve, previously untreated patients and 48 healthy controls; replication dataset including 39 first-episode patients [10 untreated patients] and 66 healthy controls) was performed. Brain network architecture was assessed by means of white matter fiber integrity measures derived from diffusion-weighted imaging (DWI) and by means of structural-functional (SC-FC) coupling measured by combining DWI and resting-state functional magnetic resonance imaging. Connectome rich club organization was found to be significantly disrupted in medication-naïve patients as compared with healthy controls (P =.012, uncorrected), with rich club connection strength (P =.032, uncorrected) and SC-FC coupling (P <.001, corrected for false discovery rate) decreased in patients. Similar results were found in the replication dataset. Our findings suggest that a disruption of rich club organization and functional dynamics may reflect an early feature of schizophrenia pathophysiology. These findings add to our understanding of the neuropathological mechanisms of schizophrenia and provide new insights into the early stages of the disorder. [ABSTRACT FROM AUTHOR]

Aberrant structural (diffusion tensor imaging [DTI]) and resting‐state functional magnetic resonance imagining connectivity are core features of bipolar disorder. However, few studies have explored the integrity agreement between structural and functional connectivity (SC–FC) in bipolar disorder. We examine SC connectivity coupling index whether could potentially provide additional clinical predictive value for bipolar disorder spectrum disorders besides the intramodality network measures. By examining the structural (DTI) and resting‐state functional network properties, as well as their coupling index, among 57 euthymic bipolar disorder patients (age 13–28 years, 18 females) and 42 age‐ and gender‐matched healthy controls (age 13–28 years, 16 females), we found that compared to controls, bipolar disorder patients showed increased structural rich‐club connectivity as well as decreased functional modularity. Importantly, the coupling strength between structural and functional connectome was decreased in patients compared to controls, which emerged as the most powerful feature discriminating the two groups. Our findings suggest that structural–functional coupling strength could serve as a valuable biological trait‐like feature for bipolar disorder over and above the intramodality network measures. Such measure can have important clinical implications for early identification of bipolar disorder individuals, and inform strategies for prevention of bipolar disorder onset and relapse. [ABSTRACT FROM AUTHOR]

We aimed to examine the whole-brain white matter connectivity and local topology of reward system nodes in patients with alcohol use disorder (AUD) and unaffected siblings, relative to healthy comparison individuals. Diffusion-weighted magnetic resonance imaging scans were acquired from 18 patients with AUD, 15 unaffected siblings of AUD patients and 15 healthy controls. Structural networks were examined using network-based statistic and connectomic analysis. Connectomic analysis showed a significant ordered difference in normalized rich club organization (AUD < Siblings < Controls). We also found rank ordered differences (Control > Sibling > AUD) for both nodal clustering coefficient and nodal local efficiency in reward system nodes, particularly left caudate, right putamen and left hippocampus. Network-based statistic analyses showed that AUD group had significantly weaker connectivity than controls in the right hemisphere, mostly in the edges connecting putamen and hippocampus with other brain regions. Our results suggest that reward system network abnormalities, especially in subcortical structures, and impairments in rich-club organization might be related to the familial predisposition for AUD. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) has been associated with altered brain structural and functional connectivity. However, little is known regarding alterations of the structural brain connectome in BD. The present study aimed to use diffusion-tensor imaging (DTI) and graph theory approaches to investigate the rich club organization and white matter structural connectome in BD. Methods: Forty-two patients with unmedicated BD depression and 59 age-, sex- and handedness-matched healthy control participants underwent DTI. The whole-brain structural connectome was constructed by a deterministic fiber tracking approach. Graph theory analysis was used to examine the group-specific global and nodal topological properties, and rich club organizations, and then nonparametric permutation tests were used for group comparisons of network parameters. Results: Compared with healthy control participants, the patients with BD showed abnormal global properties, including increased characteristic path length, and decreased global efficiency and local efficiency. Locally, the patients with BD showed abnormal nodal parameters (nodal strength, nodal efficiency, and nodal betweenness) predominantly in the parietal, orbitofrontal, occipital, and cerebellar regions. Moreover, the patients with BD showed decreased rich club and feeder connectivity density. Conclusions: Our results may reflect the disrupted white matter topological organization in the whole-brain, and abnormal regional connectivity supporting cognitive and affective functioning in depressed BD, which, in part, be due to impaired rich club connectivity. [ABSTRACT FROM AUTHOR]