Shared and specific dynamics of brain activity and connectivity in amnestic and nonamnestic mild cognitive impairment

Abstract

Aims: The present study aimed to compare temporal variability in the spontaneous fluctuations of activity and connectivity between amnestic MCI (aMCI) and nonamnestic MCI (naMCI), which enhances the understanding of their different pathophysiologies and provides targets for individualized intervention.

Methods: Sixty-five naMCI and 48 aMCI subjects and 75 healthy controls were recruited. A sliding window analysis was used to evaluate the dynamic amplitude of low-frequency fluctuations (dALFF), dynamic regional homogeneity (dReHo), and dynamic functional connectivity (dFC). The caudal/rostral hippocampus was selected as the seeds for calculating dFC.

Results: Both aMCI and naMCI exhibited abnormal dALFF, dReHo, and hippocampal dFC compared with healthy controls. Compared with individuals with naMCI, those with aMCI exhibited (1) higher dALFF variability in the right putamen, left Rolandic operculum, and right middle cingulum, (2) lower dReHo variability in the right superior parietal lobule, and (3) lower dFC variability between the hippocampus and other regions (left superior occipital gyrus, middle frontal gyrus, inferior cerebellum, precuneus, and right superior frontal gyrus). Additionally, variability in dALFF, dReHo, and hippocampal dFC exhibited different associations with cognitive scores in aMCI and naMCI patients, respectively. Finally, dReHo variability in the right superior parietal lobule and dFC variability between the right caudal hippocampus and left inferior cerebellum exhibited partially mediated effects on the different memory scores between people with aMCI and naMCI.

Conclusion: The aMCI and naMCI patients exhibited shared and specific patterns of dynamic brain activity and connectivity. The dReHo of the superior parietal lobule and dFC of the hippocampus-cerebellum contributed to the memory heterogeneity of MCI subtypes. Analyzing the temporal variability in the spontaneous fluctuations of brain activity and connectivity provided a new perspective for exploring the different pathophysiological mechanisms in MCI subtypes.

Keywords: Alzheimer's disease; MRI; dynamic networks; functional connectivity; mild cognitive impairment; neuroimaging.

FIGURE 1

Comparison of dALFF variability, dReHo variability, and dFC variability among HC, aMCI, and naMCI groups. (A) There were significant differences of dALFF variability in left superior cerebellum, right putamen, right superior temporal gyrus, left Rolandic operculum, and right middle cingulum among the three groups. (B) There were significant differences of dReHo variability in the left inferior frontal gyrus, left precuneus, and right superior parietal lobule among the three groups. (C) There were significant differences of dFC variability between the left caudal hippocampus and left superior occipital gyrus among the three groups. (D) There were significant differences of dFC variability between the left rostral hippocampus and left middle frontal gyrus among the three groups. (E) There were significant differences of dFC variability between right caudal hippocampus and left inferior cerebellum, right caudal hippocampus and left precuneus, right caudal hippocampus and right superior frontal gyrus among the three groups. dALFF, dynamic amplitude of low‐frequency fluctuation; dReHo, dynamic regional homogeneity; dFC, dynamic functional connectivity.

FIGURE 2

Post hoc comparison of dALFF variability, dReHo variability, and dFC variability among HC, aMCI, and naMCI groups. *p < 0.05, **p < 0.01, ***p < 0.001. dALFF variability, dynamic amplitude of low‐frequency fluctuation dReHo variability, dynamic regional homogeneity, dFC variability, dynamic functional connectivity. aMCI, amnestic mild cognitive impairment; naMCI, nonamnestic mild cognitive impairment; HC, healthy controls.

FIGURE 3

Correlations between dynamic indicators and cognitive scores in aMCI and naMCI groups. The dALFF variability in the right superior temporal gyrus was associated with AVLT N4 (r = −0.598, p = 0.002) in the aMCI group (A), and the dALFF variability in the right middle cingulum was associated with time of Stroop C (r = 0.464, p < 0.001) in the naMCI group (B). The dReHo variability in the right superior parietal lobule was associated with MMSE (r = −0.281, p = 0.028) (C), time of Stroop C (r = 0.411, p = 0.001) (D), and BNT (r = −0.287, p = 0.027) (E) in the naMCI group. The dFC variability between the left caudal hippocampus and left superior occipital gyrus was associated with AVLT N5 (r = −0.348, p = 0.007) (F) and SMDT (r = −0.383, p = 0.003) (G) in the naMCI group. The dFC variability between the left rostral hippocampus and left middle frontal gyrus was associated with DST (r = 0.317, p = 0.015) (H) in the aMCI group. The dFC variability between the right caudal hippocampus and left inferior cerebellum was associated with AVLT N1‐3 (r = 0.438, p = 0.022) (I), ROCF (r = 0.473, p = 0.013) (J), and BNT (r = 0.509, p = 0.007) (K) in the aMCI group. The dFC variability between the right caudal hippocampus and left precuneus was associated with AVLT N1‐3 (r = 0.508, p = 0.007) (L) and time of Stroop C (r = 0.400, p = 0.039) (M) in the aMCI group. The dFC variability between the right caudal hippocampus and right superior frontal gyrus was associated with SMDT (r = 0.474, p = 0.012) (N), VFT (r = −0.474, p = 0.013) (O), and DST (r = 0.548, p = 0.003) (P) in the aMCI group.

FIGURE 4

Mediated effect of dynamic brain function on the different cognitive scores between aMCI and naMCI groups. (A) The dFC variability between right caudal hippocampus and left inferior cerebellum partially mediated to the difference in delay recall memory score between aMCI and naMCI groups. (B) The dReHo variability right superior parietal lobule partially mediated the difference in delay recall memory score between aMCI and naMCI groups. (C) The dReHo variability right superior parietal lobule partially mediated the difference in short‐term memory score between aMCI and naMCI groups. (D) The dReHo variability right superior parietal lobule partially mediated the difference in recognition score between aMCI and naMCI groups.