Impaired cortical oscillatory coupling in mild cognitive impairment: anatomical substrate and ApoE4 effects

Our current knowledge about the anatomical substrate of impaired resting-state cortical oscillatory coupling in mild cognitive impairment is still rudimentary. Here, we show that both resting-state oscillatory coupling and its anatomical correlates clearly distinguish healthy older (HO) adults from individuals with amnestic mild cognitive impairment (aMCI). aMCI showed failures in neural-phase coupling of resting-state electroencephalographic alpha activity mostly evident between fronto-temporal and parietal regions. As oligomers of amyloid-beta (A beta) are linked to synaptic dysfunction in Alzheimer's disease (AD), we further investigated whether plasma concentrations of these oligomers (A beta(40) and A beta(42)) accounted for impaired patterns of oscillatory coupling in aMCI. Results revealed that decreased plasma A beta(42) was associated with augmented coupling of parieto-temporal regions in HO subjects, but no relationship was found in aMCI. Oscillatory coupling of frontal regions was also significantly reduced in aMCI carriers of the epsilon 4 allele of the Apolipoprotein E (ApoE) compared to epsilon 4 noncarriers, although neither neuroanatomical nor plasma A beta changes accounted for this difference. However, the abnormal pattern of oscillatory coupling in aMCI was negatively related to volume of the angular gyrus, and positively related to volume of the precuneus and the splenium of the corpus callosum. Previous evidence suggests that all these regions are neuropathological targets of AD. The current study takes that scenario one step further, suggesting that this anatomical damage could be responsible for disrupted cortical oscillatory coupling in aMCI. Together, these data shed light on how the MCI status modifies anatomo-functional relationships underlying coordination of large-scale cortical systems in the resting-state.