Analysis of Alzheimer's Disease--Related Alterations in EEG Dynamics Using Integrated Instantaneous Frequency--Amplitude Microstates

Disruptions in large-scale electroencephalography dynamics are a hallmark of Alzheimers disease. However, conventional microstate analyses rely primarily on amplitude-based features and may overlook phase-related alterations in network organization. This study examined whether integrating instantaneous frequency and instantaneous amplitude into a unified microstate framework could better characterize AD-related EEG dynamics. Resting-state electroencephalography data were recorded from 16 patients with Alzheimers disease and 18 healthy controls using 16 scalp electrodes. Instantaneous frequency and instantaneous amplitude were derived via the Hilbert transformation in the theta to alpha band, ranging from 4 to 13 Hz, spatially normalized, and jointly clustered using the k-means algorithm with k equal to 4 to define the integrated frequency and amplitude microstates. Temporal properties, including dwell time, fractional occurrence, and transition probabilities, were compared between groups. The analysis identified recurrent instantaneous frequency and instantaneous amplitude microstates. Patients with Alzheimers disease showed a reduced occurrence of the occipital-leading state with frontal amplitude enhancement and an increased occurrence of the frontal-leading, frontal-amplified state, while transition probabilities did not differ significantly. These findings suggest that impairments related to Alzheimers disease are reflected in the altered prevalence of integrated phase and amplitude brain states, supporting integrated instantaneous frequency and instantaneous amplitude microstates as a complementary approach based on electroencephalography for probing neurodegenerative network dysfunction.