Abnormal gamma frequency phase‐amplitude coupling associated with network hyperexcitability in Alzheimer’s Disease

Background Alzheimer’s disease (AD) carries an increased risk of seizures and subclinical epileptiform activity (Vossel et al. 2016). Network hyperexcitability which is the underlying phenomenon epileptic manifestations thought to contribute AD pathophysiological processes. Recently we demonstrated that greater degree neural synchronization deficits within 2-8Hz range frequency oscillations are sensitive indicators network (Ranasinghe 2021). Here, sought examine high gamma band associated with in patients. Methods Specifically, quantified Phase Amplitude Coupling (PAC) between amplitude (30-40Hz); phase oscillations) (Figure 1). We used 60s resting-state magnetoencephalography (MEG) recordings from 48 patients (n = 22, activity, AD-EPI+; n 28 without AD-EPI-), 35 age-matched controls. computed PAC for each 68 cortical regions (Desikan 2006) on source-space reconstructed MEG signal using mean vector length (Canolty 2006). Results Permutation cluster test was performed statistical comparisons vs. age matched controls, AD-EPI+ AD-EPI-. Patients showed significantly higher theta (4-8 Hz)-gamma coupling left parahippocampal right caudal-middle frontal regions. Importantly, this theta-gamma than also alpha (8-12Hz)-gamma region compared AD-EPI- 2). Conclusion These results not only identify specifically localized medial temporal earliest affected pathophysiology but delineate vulnerabilities AD.