Abnormal hippocampo-cortical theta-gamma phase-amplitude coupling in Alzheimer's disease

Cognitive decline in Alzheimer's disease (AD) may arise not only from neuronal loss but also from disrupted temporal coordination across distributed networks. Prior works in healthy individuals has shown memory-related modulation of hippocampal-cortical phase-amplitude coupling (PAC). We hypothesized alteration of resting-state hippocampo-cortical PAC in AD which relates to cognitive impairment.

Resting-state magnetoencephalography (MEG) data were obtained from 78 AD patients and 70 healthy controls. Source-reconstructed hippocampal and cortical signals were analysed using antisymmetrized bispectral methods to quantify non-linear across-site PAC.

AD patients showed significant disruptions of hippocampo-cortical PAC, particularly involving frontal, parahippocampal, and posterior-cingulate cortices. PAC measures were significantly associated with Mini-Mental State Examination scores within the AD group, with higher PAC corresponding to greater cognitive impairment in regions showing increased coupling relative to controls.

These findings demonstrate altered hippocampo-cortical temporal coordination in AD and suggest PAC as a potential electrophysiological marker of disease-related network dysfunction.