Dataset Information

Altered Functional Connectivity of Insular Subregions in Alzheimer's Disease.

ABSTRACT: Recent researches have demonstrated that the insula is the crucial hub of the human brain networks and most vulnerable region of Alzheimer's disease (AD). However, little is known about the changes of functional connectivity of insular subregions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (fMRI) data including 32 AD patients and 38 healthy controls (HCs). By defining three subregions of insula, we mapped whole-brain resting-state functional connectivity (RSFC) and identified several distinct RSFC patterns of the insular subregions: For positive connectivity, three cognitive-related RSFC patterns were identified within insula that suggest anterior-to-posterior functional subdivisions: (1) an dorsal anterior zone of the insula that exhibits RSFC with executive control network (ECN); (2) a ventral anterior zone of insula, exhibits functional connectivity with the salience network (SN); (3) a posterior zone along the insula exhibits functional connectivity with the sensorimotor network (SMN). In addition, we found significant negative connectivities between the each insular subregion and several special default mode network (DMN) regions. Compared with controls, the AD patients demonstrated distinct disruption of positive RSFCs in the different network (ECN and SMN), suggesting the impairment of the functional integrity. There were no differences of the positive RSFCs in the SN between the two groups. On the other hand, several DMN regions showed increased negative RSFCs to the sub-region of insula in the AD patients, indicating compensatory plasticity. Furthermore, these abnormal insular subregions RSFCs are closely correlated with cognitive performances in the AD patients. Our findings suggested that different insular subregions presented distinct RSFC patterns with various functional networks, which are differently affected in the AD patients.

SUBMITTER: Liu X

PROVIDER: S-EPMC5905235 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Altered Functional Connectivity of Insular Subregions in Alzheimer's Disease.

Liu Xingyun X Chen Xiaodan X Zheng Weimin W Xia Mingrui M Han Ying Y Song Haiqing H Li Kuncheng K He Yong Y Wang Zhiqun Z

Frontiers in aging neuroscience 20180411

Recent researches have demonstrated that the insula is the crucial hub of the human brain networks and most vulnerable region of Alzheimer's disease (AD). However, little is known about the changes of functional connectivity of insular subregions in the AD patients. In this study, we collected resting-state functional magnetic resonance imaging (fMRI) data including 32 AD patients and 38 healthy controls (HCs). By defining three subregions of insula, we mapped whole-brain resting-state functiona ...[more]

PMID: 29695961

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Project description:Background: Subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are regarded as part of the pre-clinical Alzheimer's disease (AD) spectrum. The insular subregional networks are thought to have diverse intrinsic connectivity patterns that are involved in cognitive and emotional processing. We set out to investigate convergent and divergent altered connectivity patterns of the insular subregions across the spectrum of pre-clinical AD and evaluated how well these patterns can differentiate the pre-clinical AD spectrum. Method: Functional connectivity (FC) analyses in insular subnetworks were carried out among 38 patients with SCD, 56 patients with aMCI, and 55 normal controls (CNs). Logistic regression analyses were used to construct models for aMCI and CN, as well as SCD and CN classification. Finally, we conducted correlation analyses to measure the relationship between FCs of altered insular subnetworks and cognition. Results: Patients with SCD presented with reduced FC in the bilateral cerebellum posterior lobe and increased FC in the medial frontal gyrus and the middle temporal gyrus. On the other hand, patients with aMCI largely presented with decreased FC in the bilateral inferior parietal lobule, the cerebellum posterior lobe, and the anterior cingulate cortex, as well as increased FC in the medial and inferior frontal gyrus, and the middle and superior temporal gyrus. Logistic regression analyses indicated that a model composed of FCs among altered insular subnetworks in patients with SCD was able to appropriately classify 83.9% of patients with SCD and CN, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.876, 81.6% sensitivity, and 81.8% specificity. A model consisting of altered insular subnetwork FCs in patients with aMCI was able to appropriately classify 86.5% of the patients with aMCI and CNs, with an AUC of 0.887, 80.4% sensitivity, and 83.6% specificity. Furthermore, some of the FCs among altered insular subnetworks were significantly correlated with episodic memory and executive function. Conclusions: Patients with SCD and aMCI are likely to share similar convergent and divergent altered intrinsic FC patterns of insular subnetworks as the pre-clinical AD spectrum, and presented with abnormalities among subnetworks. Based on these abnormalities, individuals can be correctly differentiated in the pre-clinical AD spectrum. These results suggest that alterations in insular subnetworks can be utilized as a potential biomarker to aid in conducting a clinical diagnosis of the spectrum of pre-clinical AD.

Project description:Objective: Clinically, it is very difficult to distinguish between major depressive disorder (MDD) and bipolar disorder (BD) in the period of depression. Increasing evidence shows that the insula plays an important role in depression. We aimed to compare the resting-state functional connectivity (rsFC) of insular subregions in patients with MDD and BD in depressive episodes (BDD), who had never experienced manic or hypomanic episodes when they were scanned to identify biomarkers for the identification of two diseases. Methods: We recruited 21 BDD patients, 40 MDD patients and 70 healthy controls (HC). Resting-state functional magnetic resonance imaging (rs-fMRI) was performed. BDD patients had never had manic or hypomanic episodes when they were scanned, and the diagnoses were determined by follow-up. We divided the insula into three parts including the ventral anterior insular cortex (v-AIN), dorsal anterior insular cortex (d-AIN), and posterior insula (PI). The insular-based rsFC was compared among the three groups, and an analysis of the correlation between the rsFC value and Hamilton depression and anxiety scales was carried out. Results: BDD and MDD patients demonstrated decreased rsFC from the v-AIN to the left superior/middle frontal gyrus compared with the HC group. Versus MDD and HC groups, BDD patients exhibited decreased rsFC from the v-AIN to the area in the left orbital frontal gyrus and left superior temporal gyrus (included temporal pole), from the PI to the right lateral postcentral gyrus and from all three insular subregions to the somatosensory and motor cortex. Meanwhile, a correlation between the rsFC value of the PI-right lateral postcentral gyrus and anxiety score was observed in patients. Conclusion: Our findings show BDD and MDD patients have similar decreases in insular connectivity in the dorsal lateral frontal regions, and BDD patients have specific decreased insular connectivity, especially in the somatosensory and motor cortex, which may be used as imaging evidence for clinical identification.

Project description:As a central hub in the interconnected brain network, the precuneus has been reported showing disrupted functional connectivity and hypometabolism in Alzheimer's disease (AD). However, as a highly heterogeneous cortical structure, little is known whether individual subregion of the precuneus is uniformly or differentially involved in the progression of AD. To this end, using a hybrid PET/fMRI technique, we compared resting-state functional connectivity strength (FCS) and glucose metabolism in dorsal anterior (DA_pcu), dorsal posterior (DP_pcu) and ventral (V_pcu) subregions of the precuneus among 20 AD patients, 23 mild cognitive impairment (MCI) patients, and 27 matched cognitively normal (CN) subjects. The sub-parcellation of precuneus was performed using a K-means clustering algorithm based on its intra-regional functional connectivity. For the whole precuneus, decreased FCS (p = 0.047) and glucose hypometabolism (p = 0.006) were observed in AD patients compared to CN subjects. For the subregions of the precuneus, decreased FCS was found in DP_pcu of AD patients compared to MCI patients (p = 0.011) and in V_pcu for both MCI (p = 0.006) and AD (p = 0.008) patients compared to CN subjects. Reduced glucose metabolism was found in DP_pcu of AD patients compared to CN subjects (p = 0.038) and in V_pcu of AD patients compared to both MCI patients (p = 0.045) and CN subjects (p < 0.001). For both FCS and glucose metabolism, DA_pcu remained relatively unaffected by AD. Moreover, only in V_pcu, disruptions in FCS (r = 0.498, p = 0.042) and hypometabolism (r = 0.566, p = 0.018) were significantly correlated with the cognitive decline of AD patients. Our results demonstrated a distinctively disrupted functional and metabolic pattern from ventral to dorsal precuneus affected by AD, with V_pcu and DA_pcu being the most vulnerable and conservative subregion, respectively. Findings of this study extend our knowledge on the differential roles of precuneus subregions in AD.

Project description:(1) Background: Alzheimer's disease (AD), an age-progressive neurodegenerative disease that affects cognitive function, causes changes in the functional connectivity of the default-mode network (DMN). However, the question of whether AD-related changes occur in the functional connectivity of the basal ganglia has rarely been specifically analyzed. This study aimed to measure the changes in basal ganglia functional connectivity among patients with AD and mild cognitive impairment (MCI) in their resting state using the functional connectivity density (FCD) value, the functional connectivity (FC) intensity, and the graph theory index, and to confirm their influence on clinical manifestations. (2) Methods: Resting-state functional MRI (rs-fMRI) and neuropsychological data from 48 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used for analyses. The 48 ADNI participants comprised 16 patients with AD, 16 patients with MCI, and 16 normal controls (NCs). The functional connectivity of basal ganglia was evaluated by FCDs, FC strength, and graph theory index. We compared voxel-based FCD values between groups to show specific regions with significant variation and significant connectivity from ROI conduction to ROI analysis. Pearson's correlation analyses between functional connectivity and several simultaneous clinical variables were also conducted. Additionally, receiver operating characteristic (ROC) analyses associated with classification were conducted for both FCD values and graph theory indices. (3) Results: The level of FCD in patients with cognitive impairment showed obvious abnormalities (including short-range and long-range FCD). In addition to DMN-related regions, aberrant functional connectivity was also found to be present in the basal ganglia, especially in the caudate and amygdala. The FCD values of the basal ganglia (involving the caudate and amygdala) were closely related to scores from the Mini-Mental State Examination (MMSE) and the Functional Activities Questionnaire (FAQ); meanwhile, the graph theory indices (involving global efficiency and degree) of the basal ganglia (involving the caudate, amygdala, and putamen) were also found to be closely correlated with MMSE scores. In ROC analyses of both FCD and graph theory, the amygdala was of the utmost importance in the early-stage detection of MCI; additionally, the caudate nucleus was found to be crucial in the progression of cognitive decline and AD diagnosis. (4) Conclusions: It was systematically confirmed that there is a phenomenon of change in the functional connections in the basal ganglia during cognitive decline. The findings of this study could improve our understanding of AD and MCI pathology in the basal ganglia and make it possible to propose new targets for AD treatment in further studies.

Dataset Information

Altered Functional Connectivity of Insular Subregions in Alzheimer's Disease.

Publications

Altered Functional Connectivity of Insular Subregions in Alzheimer's Disease.

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