Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study

Abstract

Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting-state functional magnetic resonance imaging (fMRI) studies have also shown that low-frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level-dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting-state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti-correlated networks that had previously been found in the resting brain. By using resting-state fMRI, our results supported previous studies that have reported an anterior-posterior disconnection phenomenon and increased within-lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks.

Figure 1

Maps of brain regions showing significant positive or negative correlations with the PCC in elderly healthy controls (A and B) and early AD patients (C and D). The statistical threshold was P 0.001 (corrected). Most of the regions that were significantly correlated with the PCC overlapped with those regions lying in the “task negative” network, and most of the regions that were significantly anti‐correlated with the PCC overlapped with those regions lying in the “task positive” network proposed by Fox et al. [2005].

Figure 2

The glass brain representation of the brain regions showing significantly different positive or negative correlations with the PCC between early AD patients and elderly healthy controls. The statistical threshold was P < 0.001 (corrected). (A) Brain regions showing significantly decreased positive correlations with the PCC in early AD patients compared with elderly healthy controls. (B) Brain regions showing significantly decreased negative correlations (closer to zero) with the PCC in early AD patients compared with elderly healthy controls.