Phase-synchronized 40 Hz transcranial electric and magnetic stimulation boosts gamma oscillations and working memory

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 (AD), may have therapeutic potential, but effective interventions remain to be determined. 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 oscillations and working memory changes. In 300 experimental sessions conducted on 30 participants, the effects of 40-Hz tACS, 40-Hz iTBS, two combined interventions (phase-locked iTBS to tACS peak sine wave or tACS trough sine wave), and a sham condition were explored. Gamma oscillatory activity (for 2 hours after intervention), working memory (3-back and 1-back load), and brain functional connectivity were monitored following each intervention. All stimulation protocols enhanced 40-Hz oscillatory power, with the iTBS-tACS Peak showing the most significant and stable increase, followed by 40-Hz tACS and 40-Hz iTBS. These stimulation protocols improved functional connectivity during the 30 minutes post-intervention while participants performed a memory task. Only the 40-Hz tACS and iTBS protocols enhanced high-load working memory speed. Concurrent, peak-synchronized 40 Hz iTBS combined with tACS and 40-Hz tACS may be a reliable protocol to induce long-lasting oscillatory activity in the gamma frequency range. These protocols may have therapeutic effects in patients with Alzheimer’s disease.