Whole-brain structure-function coupling abnormalities in mild cognitive impairment: a study combining amplitude of low-frequency fluctuations and voxel-based morphometry.

Alzheimer's disease (AD), one of the leading diseases of the nervous system, is accompanied by symptoms such as loss of memory, thinking and language skills. Both mild cognitive impairment (MCI) and very mild cognitive impairment (VMCI) are the transitional pathological stages between normal aging and AD. While the changes in whole-brain structural and functional information have been extensively investigated in AD, The impaired structure-function coupling remains unknown. The current study employed the OASIS-3 dataset, which includes 53 MCI, 90 VMCI, and 100 Age-, gender-, and education-matched normal controls (NC). Several structural and functional parameters, such as the amplitude of low-frequency fluctuations (ALFF), voxel-based morphometry (VBM), and The ALFF/VBM ratio, were used To estimate The whole-brain neuroimaging changes In MCI, VMCI, and NC. As disease symptoms became more severe, these regions, distributed in the frontal-inf-orb, putamen, and paracentral lobule in the white matter (WM), exhibited progressively increasing ALFF (ALFFNC < ALFFVMCI < ALFFMCI), which was similar to the tendency for The cerebellum and putamen in the gray matter (GM). Additionally, as symptoms worsened in AD, the cuneus/frontal lobe in the WM and the parahippocampal gyrus/hippocampus in the GM showed progressively decreasing structure-function coupling. As the typical focal areas in AD, The parahippocampal gyrus and hippocampus showed significant positive correlations with the severity of cognitive impairment, suggesting the important applications of the ALFF/VBM ratio in brain disorders. On the other hand, these findings from WM functional signals provided a novel perspective for understanding the pathophysiological mechanisms involved In cognitive decline in AD.

Hippocampus-based static functional connectivity mapping within white matter in mild cognitive impairment.

Mild cognitive impairment (MCI) is clinically characterized by memory loss and cognitive impairment closely associated with the hippocampal atrophy. Accumulating studies have confirmed the presence of neural signal changes within white matter (WM) in resting-state functional magnetic resonance imaging (fMRI). However, it remains unclear how abnormal hippocampus activity affects the WM regions in MCI. The current study employs 43 MCI, 71 very MCI (VMCI) and 87 age-, gender-, and education-matched healthy controls (HCs) from the public OASIS-3 dataset. Using the left and right hippocampus as seed points, we obtained the whole-brain functional connectivity (FC) maps for each subject. We then perform one-way ANOVA analysis to investigate the abnormal FC regions among HCs, VMCI, and MCI. We further performed probabilistic tracking to estimate whether the abnormal FC correspond to structural connectivity disruptions. Compared to HCs, MCI and VMCI groups exhibited reduced FC in the right middle temporal gyrus within gray matter, and right temporal pole, right inferior frontal gyrus within white matter. Specific dysconnectivity is shown in the cerebellum Crus II, left inferior temporal gyrus within gray matter, and right frontal gyrus within white matter. In addition, the fiber bundles connecting the left hippocampus and right temporal pole within white matter show abnormally increased mean diffusivity in MCI. The current study proposes a new functional imaging direction for exploring the mechanism of memory decline and pathophysiological mechanisms in different stages of Alzheimer's disease.