Alterations of brain local functional connectivity in amnestic mild cognitive impairment

Abstract

Background: Resting-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.

Methods: Seed-based d Mapping was used to conduct a coordinate-based meta-analysis to identify consistent ReHo alterations in aMCI.

Results: We 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.

Conclusions: This 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.

Keywords: Amnestic mild cognitive impairment; Default mode network; Meta-analysis; Regional homogeneity; Resting-state functional magnetic resonance imaging; Seed-based d mapping.

Fig. 1

Flow chart for the literature selection. Abbreviations: aMCI, amnestic mild cognitive impairment; ReHo, regional homogeneity; ROI, region of interest

Fig. 2

ReHo differences in patients with aMCI and healthy controls from the main voxel-wise meta-analysis. Abbreviations: ReHo, regional homogeneity; aMCI, amnestic mild cognitive impairment; L, left; R, right; SDM, Seed-based d Mapping; a, left parahippocampal gyrus (extending to the left hippocampus); b, right lingual gyrus (extending to the left middle occipital gyrus); c, right paracentral lobule (extending to the supplementary motor area); d, postcentral gyrus; e, right lingual gyrus; f, left insula, g, right superior parietal lobule (extending to the right angular gyrus); h, right dorsolateral prefrontal cortex; i, bilateral posterior cingulate cortex, j, left middle temporal gyrus, k, right left middle temporal gyrus. The color bar (increases of ReHo in red and decreases in green) indicates the maximum and the minimum SDM-Z values

Fig. 3

Regions with ReHo heterogeneity across studies. Abbreviations: SDM, Seed-based d Mapping; L, left; R, right; a, bilateral posterior cingulate cortex (extending to the precuneus); b, left supplementary motor area, c, right superior parietal lobule (extending to the angular gyrus); d, left fusiform gyrus, e, left lingual gyrus. The color bar indicates the maximum and the minimum SDM-Z values

Fig. 4

Meta-regression analysis of ReHo alterations against the mean MMSE scores across studies. Lower mean MMSE score in the aMCI sample was associated with lower ReHo in the right angular gyrus/supramarginal gyrus (a), right DLPFC (b), and left inferior temporal gyrus (c). The color bar indicates the maximum and minimum SDM-Z values. Each study is labeled as a dot, with larger dots symbolizing larger sample sizes. Abbreviations: ReHo, regional homogeneity; MMSE, Mini-Mental State Examination; aMCI, amnestic mild cognitive impairment; DLPFC, dorsolateral prefrontal cortex; L, left; R, right; SDM, Seed-based d Mapping

Fig. 5

Meta-regression analysis of ReHo alterations against the female ratio across studies. More females in the aMCI samples (female ratio) were related to lower ReHo in the left PCC/precuneus (a) and higher ReHo in the left pre/postcentral gyrus (b). The color bar indicates the maximum and minimum SDM-Z values. Each study is labeled as a dot, with larger dots symbolizing larger sample sizes. Abbreviations: ReHo, regional homogeneity; aMCI, amnestic mild cognitive impairment; L, left; R, right; SDM, Seed-based d Mapping

Fig. 6

Meta-regression analysis of ReHo alterations against the mean age across studies. Mean age in the aMCI sample was negatively correlated with ReHo in the right precuneus. The color bar indicates the maximum and minimum SDM-Z values. Each study is labeled as a dot, with larger dots symbolizing larger sample sizes. Abbreviations: ReHo, regional homogeneity; aMCI, amnestic mild cognitive impairment; L, left; R, right; SDM, Seed-based d Mapping

Fig. 7

Meta-regression analysis of ReHo alterations against the educational level across studies. Higher educational level in the aMCI sample was associated with lower ReHo in the left calcarine fissure/surrounding cortex (a), and higher ReHo in left fusiform gyrus/inferior temporal gyrus (b) and right angular gyrus/superior temporal gyrus (c). The color bar indicates the maximum and minimum SDM-Z values. Each study is labeled as a dot, with larger dots symbolizing larger sample sizes. Abbreviations: ReHo, regional homogeneity; aMCI, amnestic mild cognitive impairment; L, left; R, right; SDM, Seed-based d Mapping