Sensory‐evoked gamma frequency oscillations in Alzheimer’s disease patients: Biomarker and therapeutic applications

Abstract

Introduction: In our neurophysiology-based biomarker study, we are testing visually evoked steady-state oscillations (SSVEPs) in healthy young and elderly subjects, and mild cognitive impaired (MCI) and Alzheimer's disease (AD) patients. Based on recent findings from the Li-Huei Tsai Laboratory (Picower Institute, MIT) showing that 40 Hz audio/visual stimulation reverses AD-related pathologies in transgenic mice, we are evaluating the effects of 40 Hz audio/visual stimulation on brain neurophysiology in healthy subjects, and MCI and AD patients (together with clinical trials assessing impact on severity of clinical symptoms and Ab PET signals) at Cognito Therapeutics. Methods: We are testing SSVEPs, including 15, 30 and 40 Hz light stimulations, and evoked steady state oscillations in response to combined 40 Hz audio/visual stimulation using 128 or 64 channel EEG recordings, respectively. We analyze phaselocked evoked potentials, inter-trial coherence, induced oscillations and network coherence in young subjects, MCI and AD patients and age-matched healthy elderly individuals. Results: SSVEPs have been observed in healthy subjects and MCI/AD patients in response to 3 second flashing light using 15, 30 and 40 Hz stimulation frequencies. High test/re-test reliability has been established in healthy young subjects. Diminished responses to light stimulation in healthy elderly (>65 years) subjects were found compared to healthy young subjects (<30 years). Simultaneous audio/visual 40 Hz stimulation, using Cognito Stimulation System elicited 40 Hz entrainment of cortical activity over the entire 1-hour session in healthy subjects, MCI and AD patients, without adverse events either during or following SSEVP. Cortical 40 Hz entertainment was accompanied with high-intensity alpha oscillation. Following the audio/visual stimulation, the augmented alpha band power was associated with increased alpha coherence between frontooccipital and fronto-temporal regions. Conclusion: Reliable 40 Hz steady-state oscillations can be elicited and maintained in MCI and AD patients, providing an opportunity to evaluate symptomatic and disease-modifying effects of this therapy. Detecting disease relevant and individual SSVEP abnormalities can support precision medicine by customizing therapy.