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

Abstract

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 (ALFF_NC < ALFF_VMCI < ALFF_MCI), 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.

Keywords: Alzheimer’s disease; amplitude of low frequency fluctuations; structure–function coupling; voxel-based morphometry; white matter.

Figure 1

Whole-brain ALFF changes. Brain map shows the abnormal clusters within GM and WM, respectively. Histogram shows the post-hoc analysis results between NC, VMCI and MCI. (A) and (B) represent the ALFF changes within GM and WM, respectively. The statistic significant level is performed with GRF correction (voxel-level: p < 0.001, cluster-level: p < 0.01).

Figure 2

Brain regions with abnormal VBM between patient groups and NC subjects, GM (A) and WM (B) based on post-hoc T-tests. Blue and yellow colors denote decreased and increased VBM. The yellow arrow shows the corresponding brain region. The color bars indicate the T-value (GRF correction, voxel-level: p < 0.001, cluster level: p < 0.01).

Figure 3

Abnormal regions of structure–function coupling (ALFF/VBM ratio) indicators. (A) and (B) represent the abnormal regions of structure–function coupling within the GM and WM, respectively. The left side shows the abnormal brain regions and the right side shows the histogram with post-hoc analysis results. (GRF correction, voxel-level: p < 0.001, cluster level: p < 0.01).

Figure 4

Relationships between averaged abnormal clusters and MMSE scores. (A) shows the correlations between abnormal ALFF values and MMSE scores. (B) shows the correlations between abnormal coupling values and MMSE scores. X-axis = MMSE; Y-axis = ALFF or ALFF/VBM ratio.