Theta‐gamma phase‐amplitude coupling explains the advantage of auditory plus visual gamma entrainment in Alzheimer’s therapy

Abstract

AbstractBackgroundImpairment of gamma oscillations has been observed in cognitive disorders like Alzheimer’s disease (AD). Gamma entrainment using 40Hz auditory or visual stimulation has been proposed as a potential treatment for AD (Adaikkan et al., Trends in Neuroscience 2020; Sedghizadeh et al. Alzheimer’s and Dementia 2020), while simultaneous use of both modalities has been reported to show superior therapeutic results (Martorell et al., Cell 2019; Suk et al. Alzheimer’s and Dementia 2020). Gamma and theta oscillations are both produced in the hippocampal area and interact with each other. Evidence shows that the interaction between these bands leads to their phase‐amplitude coupling (PAC) in the frontal cortex (Amemiya et al., Cell Reports 2018). The current study assesses the effects of 40Hz auditory and visual stimulation on the theta‐gamma PAC, and suggests that the superior performance of multimodal entrainment can be explained by this marker.Method10 cognitively healthy participants were included in this study. Each participant was seated in a dark and quiet room and underwent three sessions of sensory stimulation (visual, auditory, and simultaneous (multimodal) visual and auditory) in a randomized order. Each session consisted of 60 trials of 5s stimulation and 5s rest. The auditory stimulation consisted of a 40Hz clicking sound modulated with a career frequency of 5kHz. The visual stimulation was generated using white LEDs flickering at 40Hz. EEG data were acquired and the theta‐gamma PAC was calculated using the time‐frequency mean vector length (tf‐MVL) method (Munia et al., Scientific Reports 2019).ResultThe PAC value for theta (4‐8Hz) and gamma oscillations near the stimulation frequency (39‐41Hz) on the Fz channel showed a significant increase during the multimodal stimulation intervals compared to the resting state, whereas the increase was not significant during the single‐modal stimulations compared to rest. The multimodal stimulation also involved more brain areas and resulted in a higher PAC compared to single‐modal stimulation.ConclusionEntraining gamma oscillations using simultaneous auditory and visual stimulation results in markedly superior theta‐gamma PAC compared to entrainment with single modalities. This superiority can explain the advantages reported for multimodal entrainment in AD therapy experiments.