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Functional and structural connectivity of the amygdala underpins locus of control in mild cognitive impairment.

ABSTRACT: Locus of control (LOC) is an important personality trait. LOC over cognitive competency reflects an individual's perceived control of desired cognitive outcomes, which is critical for maintaining successful cognitive aging. It is important to understand the neural substrates of LOC over cognitive competency in older adults, especially for individuals at high risk of dementia. Here, we characterized a cohesive functional and structural connectivity profile underlying LOC among 55 older adults with amnestic mild cognitive impairment (aMCI), combining resting-state functional magnetic resonance imaging and diffusion tensor imaging. The results showed that both functional and structural connectivity between the medial prefrontal cortex and amygdala were significantly correlated with external LOC. The functional connectivity mediated the correlation between structural connectivity and external LOC. In addition, aging-associated neurodegeneration moderated the relationship between structural connectivity and external LOC, showing that the structural connectivity was positively correlated with external LOC in low, but not high neurodegeneration. Our results suggest a critical role of the functional amygdala-frontal network, which may serve as a bridge between its white matter tract and LOC over cognitive competency in groups at high risk for dementia.

SUBMITTER: Ren P

PROVIDER: S-EPMC6083450 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Functional and structural connectivity of the amygdala underpins locus of control in mild cognitive impairment.

Ren Ping P Chapman Benjamin B Zhang Zhengwu Z Schifitto Giovanni G Lin Feng F

NeuroImage. Clinical 20180723

Locus of control (LOC) is an important personality trait. LOC over cognitive competency reflects an individual's perceived control of desired cognitive outcomes, which is critical for maintaining successful cognitive aging. It is important to understand the neural substrates of LOC over cognitive competency in older adults, especially for individuals at high risk of dementia. Here, we characterized a cohesive functional and structural connectivity profile underlying LOC among 55 older adults wit ...[more]

PMID: 30101061

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Project description:Background: The spectrum of early Alzheimer's disease (AD) is thought to include subjective cognitive impairment, early mild cognitive impairment (eMCI), and late mild cognitive impairment (lMCI). Choline dysfunction affects the early progression of AD, in which the basal nucleus of Meynert (BNM) is primarily responsible for cortical cholinergic innervation. The aims of this study were to determine the abnormal patterns of BNM-functional connectivity (BNM-FC) in the preclinical AD spectrum (SCD, eMCI, and lMCI) and further explore the relationships between these alterations and neuropsychological measures. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate FC based on a seed mask (BNM mask) in 28 healthy controls (HC), 30 SCD, 24 eMCI, and 25 lMCI patients. Furthermore, the relationship between altered FC and neurocognitive performance was examined by a correlation analysis. The receiver operating characteristic (ROC) curve of abnormal BNM-FC was used to specifically determine the classification ability to differentiate the early AD disease spectrum relative to HC (SCD and HC, eMCI and HC, lMCI and HC) and pairs of groups in the AD disease spectrum (eMCI and SCD, lMCI and SCD, eMCI and lMCI). Results: Compared with HC, SCD patients showed increased FC in the bilateral SMA and decreased FC in the bilateral cerebellum and middle frontal gyrus (MFG), eMCI patients showed significantly decreased FC in the bilateral precuneus, and lMCI individuals showed decreased FC in the right lingual gyrus. Compared with the SCD group, the eMCI group showed decreased FC in the right superior frontal gyrus (SFG), while the lMCI group showed decreased FC in the left middle temporal gyrus (MTG). Compared with the eMCI group, the lMCI group showed decreased FC in the right hippocampus. Interestingly, abnormal FC was associated with certain cognitive domains and functions including episodic memory, executive function, information processing speed, and visuospatial function in the disease groups. BNM-FC of SFG in distinguishing eMCI from SCD; BNM-FC of MTG in distinguishing lMCI from SCD; BNM-FC of the MTG, hippocampus, and cerebellum in distinguishing SCD from HC; and BNM-FC of the hippocampus and MFG in distinguishing eMCI from lMCI have high sensitivity and specificity. Conclusions: The abnormal BNM-FC patterns can characterize the early disease spectrum of AD (SCD, eMCI, and lMCI) and are closely related to the cognitive domains. These new and reliable findings will provide a new perspective in identifying the early disease spectrum of AD and further strengthen the role of cholinergic theory in AD.

Project description:Patients with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) show functional and structural connectivity alterations in the default mode network (DMN) while cerebrovascular disease (CeVD) shows functional and structural connectivity changes in the executive control network (ECN). Such disruptions are associated with memory and executive function impairment, respectively. Concurrent AD and CeVD pathology is associated with a higher rate of cognitive decline and differential neurodegenerative patterns. Together, such findings are likely reflective of different underlying pathology in AD with and without CeVD. However, few studies have examined the effect of CeVD on network functional connectivity (task-free functional magnetic resonance imaging (fMRI)) and structural connectivity (diffusion MRI) of the DMN and ECN in aMCI and AD using a hypothesis-driven multiple seed-based approach.We examined functional and structural connectivity network changes in 39 aMCI, 50 aMCI+CeVD, 47 AD, 47 AD+CeVD, and 65 healthy controls (HCs) and their associations with cognitive impairment in the executive/attention and memory domains.We demonstrate divergent DMN and ECN functional connectivity changes in CeVD and non-CeVD subjects. Compared with controls, intra-DMN hippocampal functional connectivity reductions were observed in both AD and AD+CeVD, while intra-DMN parietal and medial prefrontal-parietal functional connectivity was higher in AD+CeVD and aMCI+CeVD, but lower in AD. Intra-ECN frontal functional connectivity increases and fronto-parietal functional connectivity decreases occurred in CeVD but not non-CeVD subjects. Such functional connectivity alterations were related with cognitive impairment in a dissociative manner: intra-DMN functional connectivity changes were associated with worse cognition primarily in non-CeVD groups, while intra-ECN functional connectivity changes were associated with worse cognition primarily in CeVD groups. Additionally, CeVD and non-CeVD groups showed overlapping and distinct alterations in inter-network DMN-ECN functional connectivity depending on disease severity. In contrast to functional connectivity, CeVD groups had greater network structural connectivity damage compared with non-CeVD groups in both aMCI and AD patients. Network structural connectivity damage was associated with worse cognition.We demonstrate differential functional and structural network changes between aMCI and AD patients with and without CeVD through diverging and deleterious network-based degeneration underlying domain-specific cognitive impairment.

Project description:ObjectiveCognitive impairment occurs frequently in Parkinson's disease (PD) and negatively impacts the patient's quality of life. However, its pathophysiological mechanism remains unclear, hindering the development of new therapies. Changes in brain connectivity are related to cognitive impairment in patients with PD, with the dorsolateral prefrontal cortex (DLPFC) being considered the essential region related to PD cognitive impairment. Nevertheless, few studies have focused on the global connectivity responsible for communication with the DLPFC node, the posterior division of the middle frontal gyrus (PMFG) in patients with PD; this was the focus of this study.MethodsWe applied resting-state electroencephalography (EEG) and calculated a reliable functional connectivity measurement, the debiased weighted phase lag index (dWPLI), to examine inter-regional functional connectivity in 68 patients with PD who were classified into two groups according to their cognitive condition.ResultsWe observed that altered left and right PMFG-based functional connectivity associated with cognitive impairment in patients with PD in the theta frequency bands under the eyes closed condition (r = -0.426, p < 0.001 and r = -0.437, p < 0.001, respectively). Exploratory results based on the MoCA subdomains indicated that poorer visuospatial function was associated with higher right PMFG-based functional connectivity (r = -0.335, p = 0.005), and poorer attention function was associated with higher left and right PMFG-based functional connectivity (r = -0.380, p = 0.001 and r = -0.256, p = 0.035, respectively). Further analysis using logistic regression and receiver operating characteristic (ROC) curves found that this abnormal functional connectivity was an independent risk factor for cognitive impairment [odds ratio (OR): 2.949, 95% confidence interval (CI): 1.294-6.725, p = 0.01 for left PMFG; OR: 11.278, 95% CI: 2.578-49.335, p = 0.001 for right PMFG, per 0.1 U], and provided moderate classification power to discriminate between cognitive abilities in patients with PD [area under the ROC curve (AUC) = 0.770 for left PMFG; AUC = 0.809 for right PMFG].ConclusionThese preliminary findings indicate that abnormal PMFG-based functional connectivity patterns associated with cognitive impairment in the theta frequency bands under the eyes closed condition and altered functional connectivity patterns have the potential to act as reliable biomarkers for identifying cognitive impairment in patients with PD.

Project description:BackgroundResting-state functional magnetic resonance imaging studies using a regional homogeneity (ReHo) method have reported that amnestic mild cognitive impairment (aMCI) was associated with abnormalities in local functional connectivity. However, their results were not conclusive.MethodsSeed-based d Mapping was used to conduct a coordinate-based meta-analysis to identify consistent ReHo alterations in aMCI.ResultsWe identified 10 studies with 11 datasets suitable for inclusion, including 378 patients with aMCI and 435 healthy controls. This meta-analysis identified significant ReHo alterations in patients with aMCI relative to healthy controls, mainly within the default mode network (DMN) (bilateral posterior cingulate cortex [PCC], right angular gyrus, bilateral middle temporal gyri, and left parahippocampal gyrus/hippocampus), executive control network (right superior parietal lobule and dorsolateral prefrontal cortex), visual network (right lingual gyrus and left middle occipital gyrus), and sensorimotor network (right paracentral lobule/supplementary motor area, right postcentral gyrus and left posterior insula). Significant heterogeneity of ReHo alterations in the bilateral PCC, left parahippocampal gyrus/hippocampus, and right superior parietal lobule/angular gyrus was observed. Exploratory meta-regression analyses indicated that general cognitive function, gender distribution, age, and education level partially contributed to this heterogeneity.ConclusionsThis study provides provisional evidence that aMCI is associated with abnormal ReHo within the DMN, executive control network, visual network, and sensorimotor network. These local functional connectivity alterations suggest coexistence of functional deficits and compensation in these networks. These findings contribute to the modeling of brain functional connectomes and to a better understanding of the neural substrates of aMCI. Confounding factors merit much attention and warrant future investigations.

Project description:Background: The "primacy effect," i.e., increased memory recall for the first items of a series compared to the following items, is reduced in amnestic mild cognitive impairment (aMCI). Memory task-fMRI studies demonstrated that primacy recall is associated with higher activation of the hippocampus and temporo-parietal and frontal cortical regions in healthy subjects. Functional magnetic resonance imaging (fMRI) at resting state revealed that hippocampus functional connectivity (FC) with neocortical brain areas, including regions of the default mode network (DMN), is altered in aMCI. The present study aimed to investigate whether resting state fMRI FC between the hippocampus and cortical brain regions, especially the DMN, is associated with primacy recall performance in aMCI. Methods: A number of 87 aMCI patients underwent resting state fMRI and verbal episodic memory assessment. FC between the left or right hippocampus, respectively, and all other voxels in gray matter was mapped voxel-wise and used in whole-brain regression analyses, testing whether FC values predicted delayed primacy recall score. The delayed primacy score was defined as the number of the first four words recalled on the California Verbal Learning Test. Additionally, a partial least squares (PLS) analysis was performed, using DMN regions as seeds to identify the association of their functional interactions with delayed primacy recall. Results: Voxel-based analyses indicated that delayed primacy recall was mainly (positively) associated with higher FC between the left and right hippocampus. Additionally, significant associations were found for higher FC between the left hippocampus and bilateral temporal cortex, frontal cortical regions, and for higher FC between the right hippocampus and right temporal cortex, right frontal cortical regions, left medial frontal cortex and right amygdala (p < 0.01, uncorr.). PLS analysis revealed positive associations of delayed primacy recall with FC between regions of the DMN, including the left and right hippocampus, as well as middle cingulate cortex and thalamus (p < 0.04). In conclusion, in the light of decreased hippocampus function in aMCI, inter-hemispheric hippocampus FC and hippocampal FC with brain regions predominantly included in the DMN may contribute to residual primacy recall in aMCI.

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Functional and structural connectivity of the amygdala underpins locus of control in mild cognitive impairment.

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Functional and structural connectivity of the amygdala underpins locus of control in mild cognitive impairment.

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