Re‐evaluating the choice of gamma stimulation frequency for potential treatment of Alzheimer’s disease: Novel invisible spectral flicker evokes gamma responses at various frequencies

Abstract

AbstractBackgroundWith recent advances in the potential usage of visual gamma stimulation at 40 Hz for treatment of Alzheimer’s disease, there is reason to evaluate the use of other low gamma frequencies. The choice of 40 Hz is based on studies that describe “40 Hz” oscillations with considerable frequency variability. Results are also ambiguous on the acute effects of varying the frequency when stimulating with stroboscopic flicker in the low gamma range (30‐50 Hz). As stroboscopic visual stimulation may also affect adherence in clinical trials due to its inherent flickering, invisible spectral flicker (ISF) was proposed as a more comfortable alternative for entraining 40 Hz. This study investigates the ability of ISF to entrain gamma responses at several frequencies in the range of 36‐44 Hz.MethodTwenty healthy young volunteers were included in an electroencephalography (EEG) experiment (DTU Compute IRB Approval: COMP‐IRB‐2021‐01) with an initial eyes‐open baseline recording followed by a stimulation paradigm using ISF at nine different frequencies (36‐44 Hz, 1 Hz interval) in a randomized complete block design with five blocks. The responses were evaluated as the signal‐to‐noise ratio (SNR) averaged over the O1 and O2 electrodes at the stimulation frequency and analysed using mixed‐effect models with frequency as a fixed factor and subject and block as random factors. All two‐way interactions were included as random factors. Evoked responses were compared to baseline and between frequencies post hoc, correcting for multiple comparisons with Tukey’s method.ResultThe EEG power (Figure 1) showed that stimulus SNR values were significantly higher than baseline for all frequencies (P<.05, see Figure 2), but no stimuli resulted in significantly different SNR. There was significant subject effect (P<<.05), and one subject responded 1‐2 orders of magnitude higher than the others. This suggests higher variability between subjects than frequencies alone.ConclusionOur results indicate that ISF can induce steady‐state visually evoked potentials at several frequencies in the low gamma range of 36‐44 Hz. Across the population of participants, we found no preference or trend for any specific gamma stimulation frequency in the tested range.