Rich club analysis in the Alzheimer's disease connectome reveals a relatively undisturbed structural core network.
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ABSTRACT:
SUBMITTER: Daianu M
PROVIDER: S-EPMC4504816 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Alzheimer's disease (AD) has a preclinical phase that can last for decades prior to clinical dementia onset. Subjective cognitive decline (SCD) is regarded as the last preclinical AD stage prior to the development of amnestic mild cognitive decline (aMCI) and AD dementia (d-AD). The analysis of brain structural networks based on diffusion tensor imaging (DTI) has identified the so-called 'rich club', a set of cortical regions highly connected to each other, with other regions referred to as peripheral. It has been reported that rich club architecture is affected by regional atrophy and connectivity, which are reduced in patients with aMCI and d-AD. Methods: We recruited 62 normal controls, 47 SCD patients, 60 aMCI patients and 55 d-AD patients and collected DTI data to analyze rich-club organization. Results: We demonstrated that rich club organization was disrupted, with reduced structural connectivity among rich club nodes, in aMCI and d-AD patients but remained stable in SCD patients. In addition, SCD, aMCI and d-AD patients showed similar patterns of disrupted peripheral regions and reduced connectivity involving these regions, suggesting that peripheral regions might contribute to cognitive decline and that disruptions here could be regarded as an early marker of SCD. This organization could provide the fundamental structural architecture for complex cognitive functions and explain the low prevalence of cognitive problems in SCD patients. Conclusions: These findings reveal a disrupted pattern of the AD connectome that starts in peripheral regions and then hierarchically propagates to rich club regions, when patients show clinical symptoms. This pattern provides evidence that disruptions in rich club organization are a key factor in the progression of AD that can dynamically reflect the progression of AD, thus representing a potential biomarker for early diagnosis.
| S-EPMC6010989 | biostudies-literature
Project description:Network studies have demonstrated that a small set of highly connected regions may play a central role in global information integration, together forming a rich club organization. Given that generalized tonic-clonic seizure (GTCS) has been conceptualized as a network disorder, we hypothesized that the rich club disturbances may be related to the network abnormalities of GTCS. Here, we used graph theoretical analysis to investigate the rich club organization of both structural and functional connectome in patients with GTCS (n = 50) and healthy controls (n = 60). We further measured the level of global efficiency and clustering in rich club and non-rich club organization. We, respectively, identified a small number of highly connected hubs as rich club organization from structural and functional networks. Patients were found to exhibit significantly reduced rich club connectivity among the central hubs. Meanwhile, both structural and functional network showed changed levels of global efficiency and clustering of rich club organization in GTCS. Furthermore, in patients, lower levels of rich club connectivity were found to be correlated with longer duration of illness and seizure frequency. Together, these findings suggest that GTCS is characterized by a selective disruption of rich club organization due to the long-term injurious effects of epileptic actions on the central hub regions, which potentially contribute to a reduced level of brain integration capacity among different functional domains and an added effect of illness on a preexisting vulnerability. Our findings emphasize a central role for abnormal rich club organization in the pathophysiological mechanism underlying GTCS. Hum Brain Mapp 37:4487-4499, 2016. © 2016 Wiley Periodicals, Inc.
| S-EPMC6867540 | biostudies-literature
Project description:In network analysis, the so-called "rich club" describes the core areas of the brain that are more densely interconnected among themselves than expected by chance, and has been identified as a fundamental aspect of the human brain connectome. This is the first in-depth diffusion imaging study to investigate the rich club along with other organizational changes in the brain's anatomical network in behavioral frontotemporal dementia (bvFTD), and a matched cohort with early-onset Alzheimer's disease (EOAD). Our study sheds light on how bvFTD and EOAD affect connectivity of white matter fiber pathways in the brain, revealing differences and commonalities in the connectome among the dementias. To analyze the breakdown in connectivity, we studied three groups: 20 bvFTD, 23 EOAD, and 37 healthy elderly controls. All participants were scanned with diffusion-weighted magnetic resonance imaging (MRI), and based on whole-brain probabilistic tractography and cortical parcellations, we analyzed the rich club of the brain's connectivity network. This revealed distinct patterns of disruption in both forms of dementia. In the connectome, we detected less disruption overall in EOAD than in bvFTD [false discovery rate (FDR) critical Pperm = 5.7 × 10(-3) , 10,000 permutations], with more involvement of richly interconnected areas of the brain (chi-squared P = 1.4 × 10(-4) )-predominantly posterior cognitive alterations. In bvFTD, we found a greater spread of disruption including the rich club (FDR critical Pperm = 6 × 10(-4) ), but especially more peripheral alterations (chi-squared P = 6.5 × 10(-3) ), particularly in medial frontal areas of the brain, in line with the known behavioral socioemotional deficits seen in these patients.
| S-EPMC4883024 | biostudies-literature
Project description:Emerging research indicates interruptions in the wiring organization of the brain network in Mild cognitive impairment (MCI) and Alzheimer's disease (AD). Due to the important role of rich-club organization in distinguishing abnormalities of AD patients and the close relationship between structural connectivity (SC) and functional connectivity (FC), our study examined whether changes in SC-FC coupling and the relationship with abnormal rich-club organizations during the development of diseases may contribute to the pathophysiology of AD. Structural diffusion-tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI) were performed in 38 normal controls (NCs), 40 MCI patients and 19 AD patients. Measures of the rich-club structure and its role in global structural-functional coupling were administered. Our study found decreased levels of feeder and local connectivity in MCI and AD patients, which were the main contributing factors to the lower efficiency of the brain structural network. Another important finding was that we have more accurately characterized the changing pattern of functional brain dynamics. The enhanced coupling between SC and FC in MCI and AD patients might be due to disruptions in optimal structural organization. More interestingly, we also found increases in the SC-FC coupling for feeder and local connections in MCI and AD patients. SC-FC coupling also showed significant differences between MCI and AD patients, mainly between the abnormal feeder connections. The connection density and coupling strength were significantly correlated with clinical metrics in patients. The present findings enhanced our understanding of the neurophysiologic mechanisms associated with MCI and AD.
| S-EPMC7013042 | biostudies-literature
Project description: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.
| S-EPMC9435005 | biostudies-literature
Project description:Chromosome 22q11.2 deletion syndrome (22q11DS) is a genetic disease known to lead to cerebral structural alterations, which we study using the framework of the macroscopic white-matter connectome. We create weighted connectomes of 44 patients with 22q11DS and 44 healthy controls using diffusion tensor magnetic resonance imaging, and perform a weighted graph theoretical analysis. After confirming global network integration deficits in 22q11DS (previously identified using binary connectomes), we identify the spatial distribution of regions responsible for global deficits. Next, we further characterize the dysconnectivity of the deficient regions in terms of sub-network properties, and investigate their relevance with respect to clinical profiles. We define the subset of regions with decreased nodal integration (evaluated using the closeness centrality measure) as the affected core (A-core) of the 22q11DS structural connectome. A-core regions are broadly bilaterally symmetric and consist of numerous network hubs - chiefly parietal and frontal cortical, as well as subcortical regions. Using a simulated lesion approach, we demonstrate that these core regions and their connections are particularly important to efficient network communication. Moreover, these regions are generally densely connected, but less so in 22q11DS. These specific disturbances are associated to a rerouting of shortest network paths that circumvent the A-core in 22q11DS, "de-centralizing" the network. Finally, the efficiency and mean connectivity strength of an orbito-frontal/cingulate circuit, included in the affected regions, correlate negatively with the extent of negative symptoms in 22q11DS patients, revealing the clinical relevance of present findings. The identified A-core overlaps numerous regions previously identified as affected in 22q11DS as well as in schizophrenia, which approximately 30-40% of 22q11DS patients develop.
| S-EPMC4711395 | biostudies-literature
Project description:Suicide ideation (SI) is a most high-risk clinical sign for major depressive disorder (MDD). However, whether the rich-club network organization as a core structural network is associated with SI and how the related neural circuits are distributed in MDD patients remain unknown. Total 177 participants including 69 MDD patients with SI (MDDSI), 58 MDD without SI (MDDNSI) and 50 cognitively normal (CN) subjects were recruited and completed neuropsychological tests and diffusion-tensor imaging scan. The rich-club organization was identified and the global and regional topological properties of structural networks, together with the brain connectivity of specific neural circuit architectures, were analyzed. Further, the support vector machine (SVM) learning was applied in classifying MDDSI or MDDNSI from CN subjects. MDDSI and MDDNSI patients both exhibited disrupted rich-club organizations. However, MDDSI patients showed that the differential network was concentrated on the non-core low-level network and significantly destroyed betweeness centrality was primarily located in the regional non-hub regions relative to MDDNSI patients. The differential structural network connections involved the superior longitudinal fasciculus and the corpus callosum were incorporated in the cognitive control circuit and default mode network. Finally, the feeder serves as a potentially powerful indicator for distinguishing MDDSI patients from MDDNSI or CN subjects. The altered rich-club organization provides new clues to understand the underlying pathogenesis of MDD patients, and the feeder was useful as a diagnostic neuroimaging biomarker for differentiating MDD patients with or without SI.
| S-EPMC8068724 | biostudies-literature
Project description:Ischemic stroke involves multiple pathophysiological mechanisms with complex interactions. Efforts to decipher those mechanisms and understand the evolution of cerebral injury is key for developing successful interventions. In an innovative approach, we use literature mining, natural language processing and systems biology tools to construct, annotate and curate a brain ischemia interactome. The curated interactome includes proteins that are deregulated after cerebral ischemia in human and experimental stroke. Network analysis of the interactome revealed a rich-club organization indicating the presence of a densely interconnected hub structure of prominent contributors to disease pathogenesis. Functional annotation of the interactome uncovered prominent pathways and highlighted the critical role of the complement and coagulation cascade in the initiation and amplification of injury starting by activation of the rich-club. We performed an in-silico screen for putative interventions that have pleiotropic effects on rich-club components and we identified estrogen as a prominent candidate. Our findings show that complex network analysis of disease related interactomes may lead to a better understanding of pathogenic mechanisms and provide cost-effective and mechanism-based discovery of candidate therapeutics.
| S-EPMC4550934 | biostudies-literature
Project description: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.
| S-EPMC9263507 | biostudies-literature
Project description:The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called "rich-club" are crucial high efficiency communication hubs in the brain. The abnormal rich-club organization can reflect underlying abnormal brain function and metabolism, which receives increasing attention. Diabetes is one of the risk factors for neurological diseases, and most individuals with prediabetes will develop overt diabetes within their lifetime. However, the gradual impact of hyperglycemia on brain structures, including rich-club organization, remains unclear. We hypothesized that the brain follows a special disrupted pattern of rich-club organization in prediabetes and diabetes. We used cross-sectional baseline data from the population-based PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study, which included 2218 participants with a mean age of 61.3 ± 6.6 years and 54.1% females comprising 1205 prediabetes, 504 diabetes, and 509 normal control subjects. The rich-club organization and network properties of the structural networks derived from diffusion tensor imaging data were investigated using a graph theory approach. Linear mixed models were used to assess associations between rich-club organization disruptions and the subjects' glucose status. Based on the graphical analysis methods, we observed the disrupted pattern of rich-club organization was from peripheral regions mainly located in frontal areas to rich-club regions mainly located in subcortical areas from prediabetes to diabetes. The rich-club organization disruptions were associated with elevated glucose levels. These findings provided more details of the process by which hyperglycemia affects the brain, contributing to a better understanding of the potential neurological consequences. Furthermore, the disrupted pattern observed in rich-club organization may serve as a potential neuroimaging marker for early detection and monitoring of neurological disorders in individuals with prediabetes or diabetes.
| S-EPMC10839741 | biostudies-literature