Spontaneous Brain Activity in Type 2 Diabetics Revealed by Amplitude of Low-Frequency Fluctuations and Its Association with Diabetic Vascular Disease: A Resting-State fMRI Study

Abstract

PurposeTo investigate correlations between altered spontaneous brain activity, diabetic vascular disease, and cognitive function for patients with type 2 diabetes mellitus (T2DM) using resting-state functional magnetic resonance imaging (rs-fMRI).MethodsRs-fMRI was performed for T2DM patients (n = 26) and age-, gender-, and education-matched non-diabetic control subjects (n = 26). Amplitude of low frequency fluctuations (ALFF) were computed from fMRI signals to measure spontaneous neuronal activity. Differences in the ALFF patterns between patients and controls, as well as their correlations with clinical variables, were evaluated.ResultsCompared with healthy controls, T2DM patients exhibited significantly decreased ALFF values mainly in the frontal and parietal lobes, the bilateral thalumi, the posterior lobe of the cerebellum, and increased ALFF values mainly in the visual cortices. Furthermore, lower ALFF values in the left subcallosal gyrus correlated with lower ankle-brachial index values (r = 0.481, p = 0.020), while lower ALFF values in the bilateral medial prefrontal gyri correlated with higher urinary albumin-creatinine ratio (r = −0.418, p = 0.047). In addition, most of the regions with increased ALFF values in the visual cortices were found to negatively correlate with MoCA scores.ConclusionsThese results confirm that ALFF are altered in many brain regions in T2DM patients, and this is associated with the presence of diabetic vascular disease and poor cognitive performance. These findings may provide additional insight into the neurophysiological mechanisms that mediate T2DM-related cognitive dysfunction, and may also serve as a reference for future research.

Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study

“…Consistent with this Wang et.al. showed increased spontaneous neuronal activity in the visual cortices within the occipital lobe of T2D subjects [38]. In contrast, Cui et.al.…”

Disrupted resting-state attentional networks in T2DM patients

“…Hoogenboom et al combined diffusion tensor imaging and fMRI to identify the white matter alterations in T2DM patients that correlated with disrupted functional connectivity in the default-mode network 40 . In addition, to date, three data-driven studies have investigated the potential changes in the brain of T2DM: previous work from our laboratory used the amplitude of low frequency fluctuations (ALFF) method to investigate the neuronal activity of T2DM patients 22 , Wang et al 41 used the same method to further investigate the effects of diabetic vascular disease on the brain, and Cui et al 42 combined the ALFF with regional homogeneity (ReHo) methods and also observed alterations in the diabetic brain. ALFF and ReHo of the BOLD signal are thought to be indicators of the intensity and temporal synchronization of regional spontaneous neuronal activity in the whole brain 43 44 , whereas functional connectivity analysis describes spatiotemporal correlations between spatially distinct brain regions, as well as shows the correlations of voxel signals with the signal of a particular component 45 46 ; higher functional connectivity between certain regions represents a higher degree of involvement of a particular network 47 .…”

Impact of diabetes on cognitive function and brain structure

“…Interestingly, this finding was present in the absence of structural brain changes and was associated with worse memory performance and executive functioning. Disturbances of low‐frequency fluctuations have been observed in several additional brain areas . For instance, smaller fluctuations in the bilateral middle temporal gyrus have been associated with higher A1C values, impaired β‐cell function, and poor neurocognitive performances …”

“…Disturbances of low-frequency fluctuations have been observed in several additional brain areas. 92,93 For instance, smaller fluctuations in the bilateral middle temporal gyrus have been associated with higher A1C values, impaired ␤-cell function, and poor neurocognitive performances. 92 It is likely that the microvascular complications of diabetes largely contribute to the development of brain functional abnormalities, which possibly even precede the cognitive decline observed in T2DM.…”