Dynamic Changes of Amplitude of Low-Frequency Fluctuations in Patients With Diabetic Retinopathy

Abstract

Background: Growing evidence demonstrate that diabetic retinopathy (DR) patients have a high risk of cognitive decline and exhibit abnormal brain activity. However, neuroimaging studies thus far have focused on static cerebral activity changes in DR patients. The characteristics of dynamic cerebral activity in patients with DR are poorly understood. Purpose: The purpose of the study was to investigate the dynamic cerebral activity changes in patients with DR using the dynamic amplitude of low-frequency fluctuation (dALFF) method. Materials and methods: Thirty-four DR patients (18 men and 16 women) and 38 healthy controls (HCs) (18 males and 20 females) closely matched in age, sex, and education were enrolled in this study. The dALFF method was used to investigate dynamic intrinsic brain activity differences between the DR and HC groups. Results: Compared with HCs, DR patients exhibited increased dALFF variability in the right brainstem, left cerebellum_8, left cerebellum_9, and left parahippocampal gyrus. In contrast, DR patients exhibited decreased dALFF variability in the left middle occipital gyrus and right middle occipital gyrus. Conclusion: Our study highlighted that DR patients showed abnormal variability of dALFF in the visual cortices, cerebellum, and parahippocampal gyrus. These findings suggest impaired visual and motor and memory function in DR individuals. Thus, abnormal dynamic spontaneous brain activity might be involved in the pathophysiology of DR.

Keywords: diabetic retinopathy; dynamic amplitude of low-frequency fluctuation; functional magnetic resonance imaging; functional network; network centrality.

Figure 1

Illustration of analysis steps and temporal variability of dALFF pattern. (A) The pre-processed full-length BOLD fMRI time series was segmented into several sliding windows (50TRs). The temporal variability of the dALFF was defined as the variance of dALFF maps across the sliding windows. The pattern of temporal variability of the dALFF in the DR group (B) and HC group (C). The different temporal variability of dALFF between two groups. (D) dALFF, dynamic amplitude of low-frequency fluctuation; DR, Diabetic Retinopathy; HC, Health Controls.

Figure 2

Spatial patterns of dALFF variance were observed at the group level in DR and HC groups. Within group mean dALFF variance maps within the DR (A) and HC (B). dALFF, dynamic amplitude of low-frequency fluctuation; DR, Diabetic Retinopathy; HC, Health Controls; L, left; R, right.

Figure 3

Comparison of different dALFF values between the DR group and HC group. Significant dALFF value differences were observed in the R-BS, L-CER_8, L-CER_9, L-PHG, L-MOG, R-MOG (A,B). The mean values of altered dALFF values between the DR and HC groups (C). dALFF, dynamic amplitude of low-frequency fluctuation; DR, Diabetic Retinopathy; HC, Health Controls; GRF, Gaussian random field; BS, Brainstem; CER, Cerebellum; PHG, Parahippocampal; MOG, middle occipital gyrus; L, left; R, right.

Figure 4

The temporal properties of dALFF patterns between the DR group and HC group. The K-means clustering method with three clusters (A). Transition matrices of different states (B). The number of transitions between states (C). Mean dwell time (D). dALFF, dynamic amplitude of low-frequency fluctuation; DR, Diabetic Retinopathy; HC, Health Controls.

Figure 5

ROC curve analysis of the mean dALFF for altered brain regions. ROC curve in dALFF values: DR>HC, for R-BS 0.874 (P < 0.001; 95% CI: 0.794–0.955); for L-CER_8 0.859 (P < 0.001; 95% CI: 0.769–0.948); for L-CER_9 0.809 (P < 0.001; 95% CI: 0.708–0.910); for L-PHG 0.806 (P < 0.001; 95% CI: 0.701–0.910); (A) DR<HC, for L-MOG 0.800 (P < 0.001; 95% CI: 0.699–0.901); for R-MOG 0.803 (P < 0.001; 95% CI: 0.702–0.904); (B). ROC, receiver operating characteristic; dALFF, dynamic amplitude of low-frequency fluctuation; AUC, area under the curve; BS, Brainstem; CER, Cerebelum; PHG, Parahippocampal; MOG, middle occipital gyrus; L, left; R, right.