Dataset Information

Dynamic changes of functional segregation and integration in vulnerability and resilience to schizophrenia.

ABSTRACT: Schizophrenia (SZ) is a highly heritable disease with neurodevelopmental origins and significant functional brain network dysfunction. Functional network is heavily influenced by neurodevelopment processes and can be characterized by the degree of segregation and integration. This study examines functional segregation and integration in SZ and their first-degree relatives (high risk [HR]) to better understand the dynamic changes in vulnerability and resiliency, and disease markers. Resting-state functional magnetic resonance imaging data acquired from 137 SZ, 89 HR, and 210 healthy controls (HCs). Small-worldness ? was computed at voxel level to quantify balance between segregation and integration. Interregional functional associations were examined based on Euclidean distance between regions and reflect degree of segregation and integration. Distance strength maps were used to localize regions of altered distance-based functional connectivity. ? was significantly decreased in SZ compared to HC, with no differences in high risk (HR). In three-group comparison, significant differences were noted in short-range connectivity (primarily in the primary sensory, motor and their association cortices, and the thalamus) and medium/long-range connectivity (in the prefrontal cortices [PFCs]). Decreased short- and increased medium/long-range connectivity was found in SZ. Decreased short-range connectivity was seen in SZ and HR, while HR had decreased medium/long-range connectivity. We observed disrupted balance between segregation and integration in SZ, whereas relatively preserved in HR. Similarities and differences between SZ and HR, specific changes of SZ were found. These might reflect dynamic changes of segregation in primary cortices and integration in PFCs in vulnerability and resilience, and disease markers in SZ.

SUBMITTER: Duan J

PROVIDER: S-EPMC6865589 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Dynamic changes of functional segregation and integration in vulnerability and resilience to schizophrenia.

Duan Jia J Xia Mingrui M Womer Fay Y FY Chang Miao M Yin Zhiyang Z Zhou Qian Q Zhu Yue Y Liu Zhuang Z Jiang Xiaowei X Wei Shengnan S Anthony O'Neill Francis F He Yong Y Tang Yanqing Y Wang Fei F

Human brain mapping 20190115 7

Schizophrenia (SZ) is a highly heritable disease with neurodevelopmental origins and significant functional brain network dysfunction. Functional network is heavily influenced by neurodevelopment processes and can be characterized by the degree of segregation and integration. This study examines functional segregation and integration in SZ and their first-degree relatives (high risk [HR]) to better understand the dynamic changes in vulnerability and resiliency, and disease markers. Resting-state ...[more]

PMID: 30648317

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Project description:BackgroundPrevious studies on brain functional connectivity have revealed the neural physiopathology in patients with pontine stroke (PS). However, those studies focused only on the static features of intrinsic fluctuations, rather than on the time-varying effects throughout the entire scan. In the present study, we sought to explore the underlying mechanism of PS using the dynamic functional network connectivity (dFNC) method.MethodsResting-state functional magnetic resonance imaging (fMRI) data were collected from 58 patients with PS and 52 healthy controls (HC). Independent component analysis (ICA), the sliding window method, and k-means clustering analysis were performed to extract different functional networks, to calculate dFNC matrices, and to estimate distinct dynamic connectivity states. Additionally, temporal features were compared between the two groups in each state to explore the brain's preference for different dynamic connectivity states in PS, and global and local efficiency were compared among states to explore the differences of topologic organization across different dFNC states. The correlations between clinical scales and the temporal features that differed between the two groups also were calculated.ResultsThe dFNC analyses suggested four recurring states; in two of these states, the PS group showed a different duration from that of the HC group. Patients with PS spent significantly more time in a sparsely connected state (State 1), which was characterized by relatively low levels of connectivity within and between all brain networks. In contrast, patients with PS spent significantly less time in a highly segregated state (State 2), which was characterized by high levels of positive connectivities within primary perceptional domains and within higher cognitive control domains, and by high levels of negative inter-functional connectivities (inter-FCs) among primary perceptional and higher cognitive control domains. Additionally, the dwell time in State 2 was positively correlated with HC group's long-term memory scores in the Rey Auditory Verbal Learning Test (RAVLT-L), whereas there was no correlation between the State-2 dwell time and RAVLT-L scores in the PS group. Furthermore, the sparsely connected state and the highly segregated state mentioned above had the highest global efficiency and the highest local efficiency among the four states, respectively.ConclusionsIn summary, we observed a preference in the aberrant brain for dynamic connectivity states with different network topologic organization in patients with PS, indicating abnormal functional segregation and integration of the whole brain and confirming the imperfection of functional network connectivity in patients with PS. These findings provide new evidence for the dynamic neural mechanisms underlying clinical symptoms in patients with PS.

Project description:Cognitive resilience is an important modulating factor of cognitive decline in Alzheimer's disease, but the functional brain mechanisms that support cognitive resilience remain elusive. Given previous findings in normal ageing, we tested the hypothesis that higher segregation of the brain's connectome into distinct functional networks represents a functional mechanism underlying cognitive resilience in Alzheimer's disease. Using resting-state functional MRI, we assessed both resting-state functional MRI global system segregation, i.e. the balance of between-network to within-network connectivity, and the alternate index of modularity Q as predictors of cognitive resilience. We performed all analyses in two independent samples for validation: (i) 108 individuals with autosomal dominantly inherited Alzheimer's disease and 71 non-carrier controls; and (ii) 156 amyloid-PET-positive subjects across the spectrum of sporadic Alzheimer's disease and 184 amyloid-negative controls. In the autosomal dominant Alzheimer's disease sample, disease severity was assessed by estimated years from symptom onset. In the sporadic Alzheimer's sample, disease stage was assessed by temporal lobe tau-PET (i.e. composite across Braak stage I and III regions). In both samples, we tested whether the effect of disease severity on cognition was attenuated at higher levels of functional network segregation. For autosomal dominant Alzheimer's disease, we found higher functional MRI-assessed system segregation to be associated with an attenuated effect of estimated years from symptom onset on global cognition (P = 0.007). Similarly, for patients with sporadic Alzheimer's disease, higher functional MRI-assessed system segregation was associated with less decrement in global cognition (P = 0.001) and episodic memory (P = 0.004) per unit increase of temporal lobe tau-PET. Confirmatory analyses using the alternate index of modularity Q revealed consistent results. In conclusion, higher segregation of functional connections into distinct large-scale networks supports cognitive resilience in Alzheimer's disease.

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Dynamic changes of functional segregation and integration in vulnerability and resilience to schizophrenia.

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Dynamic changes of functional segregation and integration in vulnerability and resilience to schizophrenia.

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