Phase-synchronized 40 Hz tACS and iTBS effects on gamma oscillations

Gamma oscillations play a crucial role in core cognitive functions such as memory processes. Enhancing gamma oscillatory activity, which is reduced in Alzheimer's Disease, may have therapeutic potential, but effective interventions remain to be determined. Previous studies have shown that phase-synchronized electric and magnetic stimulation boosts brain oscillatory activities at theta, alpha, and delta frequency bands in different ways. The high-frequency gamma frequency band remains to be investigated. This study applies novel noninvasive brain stimulation techniques, namely phase-locked 40-Hz intermittent theta-burst stimulation (iTBS) and transcranial alternating current stimulation (tACS), and explores gamma oscillation changes in the brain. Thirty healthy young participants randomly underwent 40-Hz tACS (1), 40-Hz iTBS (2), two combined interventions (phase-locked iTBS to tACS peak sine wave or tACS trough sine wave) (3-4), and a sham condition (5). The target regions were the left and right dorsolateral prefrontal cortex and were stimulated by simultaneous tACS and iTBS. Gamma oscillatory activities (for 2 hours after intervention) were monitored following each intervention. Our results show that all stimulation protocols enhanced 40-Hz oscillatory power. The iTBS-tACS Peak shows the most significant and stable increase in gamma oscillatory activities (up to 2 hours), followed by 40-Hz tACS and 40-Hz iTBS. 40-Hz tACS and 40-Hz iTBS had the strongest acute effects (up to 30 minutes) on induced gamma oscillations, while 40-Hz tACS most consistently induced gamma oscillations for up to 2 hours in overall resting EEG data. Phase-synchronizing iTBS with tACS at 40 Hz and the very 40 Hz tACS alone targeting the dorsolateral prefrontal cortex may be a viable approach for inducing and stabilizing gamma oscillatory activity, particularly in conditions where endogenous gamma oscillations are attenuated, such as Alzheimer's Disease.