Multiple cross-frequency coupling analysis of resting-state EEG in patients with mild cognitive impairment and Alzheimer’s disease

INTRODUCTION: Electroencephalographic (EEG) abnormalities are seen in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) with characteristic features of cognitive impairment. The most common findings of EEG features in AD and MCI patients are increased relative power of slow oscillations (delta and theta rhythms) and decreased relative power of fast oscillations (alpha, beta and gamma rhythms). However, impairments in cognitive processes in AD and MCI are not sufficiently reflected by brain oscillatory activity in a particular frequency band. MCI patients are at high risk of progressing to AD. Cross-frequency coupling (CFC), which refers to coupling between different frequency bands, is a crucial tool for comprehending changes in brain oscillations and cognitive performance. CFC features exhibit some specificity in patients with AD and MCI, but a comparison between CFC features in individuals with these disorders is still lacking. The aim of this study was to explore changes in CFC properties in MCI and AD and to explore the relationship between CFC properties and multiple types of cognitive functional performance. METHODS: We recorded resting-state EEG (rsEEG) signals in 46 MCI patients, 43 AD patients, and 43 cognitively healthy controls (HCs) and analyzed the changes in CFC as well as the relationship between CFC and scores on clinical tests of cognitive function. RESULTS AND DISCUSSION: Multiple couplings between low-frequency oscillations and high-frequency oscillations were found to be significantly enhanced in AD patients compared to those of HCs and MCI, while delta-gamma as well as theta-gamma couplings in the right temporal and parietal lobes were significantly enhanced in MCI patients compared to HCs. Moreover, theta-gamma coupling in the right temporal lobe tended to be stronger in MCI patients than in HCs, and it was stronger in AD than in MCI. Multiple CFC properties were found to correlate significantly with various cognitive domains, especially the memory function domain. Overall, these findings suggest that AD and MCI patients must use more neural resources to maintain a resting brain state and that alterations in theta-gamma coupling in the temporal lobe become progressively obvious during disease progression and are likely to be a valuable indicator of MCI and AD pathology.