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Morphological, Structural, and Functional Networks Highlight the Role of the Cortical-Subcortical Circuit in Individuals With Subjective Cognitive Decline.

ABSTRACT: Subjective cognitive decline (SCD) is considered the earliest stage of the clinical manifestations of the continuous progression of Alzheimer's Disease (AD). Previous studies have suggested that multimodal brain networks play an important role in the early diagnosis and mechanisms underlying SCD. However, most of the previous studies focused on a single modality, and lacked correlation analysis between different modal biomarkers and brain regions. In order to further explore the specific characteristic of the multimodal brain networks in the stage of SCD, 22 individuals with SCD and 20 matched healthy controls (HCs) were recruited in the present study. We constructed the individual morphological, structural and functional brain networks based on 3D-T1 structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively. A t-test was used to select the connections with significant difference, and a multi-kernel support vector machine (MK-SVM) was applied to combine the selected multimodal connections to distinguish SCD from HCs. Moreover, we further identified the consensus connections of brain networks as the most discriminative features to explore the pathological mechanisms and potential biomarkers associated with SCD. Our results shown that the combination of three modal connections using MK-SVM achieved the best classification performance, with an accuracy of 92.68%, sensitivity of 95.00%, and specificity of 90.48%. Furthermore, the consensus connections and hub nodes based on the morphological, structural, and functional networks identified in our study exhibited abnormal cortical-subcortical connections in individuals with SCD. In addition, the functional networks presented more discriminative connections and hubs in the cortical-subcortical regions, and were found to perform better in distinguishing SCD from HCs. Therefore, our findings highlight the role of the cortical-subcortical circuit in individuals with SCD from the perspective of a multimodal brain network, providing potential biomarkers for the diagnosis and prediction of the preclinical stage of AD.

SUBMITTER: Xu X

PROVIDER: S-EPMC8299728 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose: To investigate the dynamic functional connectivity (DFC) and static parameters of graph theory in individuals with subjective cognitive decline (SCD) and the associations of DFC and topological properties with cognitive performance. Methods: Thirty-three control subjects and 32 SCD individuals were enrolled in this study, and neuropsychological evaluations and resting-state functional magnetic resonance imaging scanning were performed. Thirty-three components were selected by group independent component analysis to construct 7 functional networks. Based on the sliding window approach and k-means clustering, distinct DFC states were identified. We calculated the temporal properties of fractional windows in each state, the mean dwell time in each state, and the number of transitions between each pair of DFC states. The global and local static parameters were assessed by graph theory analysis. The differences in DFC and topological metrics, and the associations of the altered neuroimaging measures with cognitive performance were assessed. Results: The whole cohort demonstrated 4 distinct connectivity states. Compared to the control group, the SCD group showed increased fractional windows and an increased mean dwell time in state 4, characterized by hypoconnectivity both within and between networks. The SCD group also showed decreased fractional windows and a decreased mean dwell time in state 2, dominated by hyperconnectivity within and between the auditory, visual and somatomotor networks. The number of transitions between state 1 and state 2, between state 2 and state 3, and between state 2 and state 4 was significantly reduced in the SCD group compared to the control group. No significant differences in global or local topological metrics were observed. The altered DFC properties showed significant correlations with cognitive performance. Conclusion: Our findings indicated DFC network reconfiguration in the SCD stage, which may underlie the early cognitive decline in SCD subjects and serve as sensitive neuroimaging biomarkers for the preclinical detection of individuals with incipient Alzheimer's disease.

Project description:Angelman syndrome (AS) is a neurodevelopmental disorder with serious seizures. We aim to explore the brain morphometry of patients with AS and figure out whether the seizure is associated with brain development. Seventy-three patients and 26 healthy controls (HC) underwent high-resolution structural brain MRI. Group differences between the HC group and the AS group and also between AS patients with seizure (AS-Se) and age-matched AS patients with non-seizure (AS-NSe) were compared. The voxel-based and surface-based morphometry analyses were used in our study. Gray matter volume, cortical thickness (CTH), and local gyrification index (LGI) were assessed to analyze the cortical and subcortical structure alteration in the AS brain. Firstly, compared with the HC group, children with AS were found to have a significant decrease in gray matter volume in the subcortical nucleus, cortical, and cerebellum. However, the gray matter volume of AS patients in the inferior precuneus was significantly increased. Secondly, patients with AS had significantly increased LGI in the whole brain as compared with HC. Thirdly, the comparison of AS-Se and the AS-NSe groups revealed a significant decrease in caudate volume in the AS-Se group. Lastly, we further selected the caudate and the precuneus as ROIs for volumetric analysis, the AS group showed significantly increased LGI in the precuneus and reduced CTH in the right precuneus. Between the AS-Se and the AS-NSe groups, the AS-Se group exhibited significantly lower density in the caudate, while only the CTH in the left precuneus showed a significant difference. These results revealed cortical and subcortical morphological alterations in patients with AS, including globally the decreased brain volume in the subcortical nucleus, the increased gray matter volume of precuneus, and the whole-brain increase of LGI and reduction of CTH. The abnormal brain pattern was more serious in patients with seizures, suggesting that the occurrence of seizures may be related to abnormal brain changes.

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Morphological, Structural, and Functional Networks Highlight the Role of the Cortical-Subcortical Circuit in Individuals With Subjective Cognitive Decline.

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