Induction and stabilization of delta frequency brain oscillations by phase-synchronized rTMS and tACS

Abstract

Background: Brain oscillations in the delta frequency band have been linked with deep sleep and consolidation of declarative memory during sleep. However, the causal relationship of these associations remains not competely clarified, primarily due to constraints by technical limitations of brain stimulation approaches suited to induce and stabilize respective oscillatory activity in the human brain. The objective of this study was to establish a non-invasive brain stimulation protocol capable of reliably inducing, and stabilizing respective oscillatory activity in the delta frequency range. Hypothesis: We aimed to develop an efficient non-invasive brain stimulation (NIBS) protocol for delta frequency induction and stabilization via concurrent, phase-locked repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS). We hypothesized that rTMS induces oscillatory resting-state activity in the delta frequency and that tACS stabilizes this effect, as has been shown before for alpha and theta frequencies. Methods: 19 healthy participants took part in a repeated-measures experimental protocol. We applied rTMS pulses synchronized with the peak or trough phase of 0.75Hz tACS over the bilateral prefrontal cortex. Resting state EEG in eyes-open (EO) and eyes-closed (EC) conditions was recorded before, immediately after and every 10 min for up to 1 h after intervention. Results: rTMS phase-synchronized to the trough of the tACS waveform significantly increased delta frequency activity for up to 60 min in both EO and EC conditions after stimulation. The effects extended from frontal to temporal regions and this enhancement of oscillatory activity was shown to be specific for the delta frequency range. Conclusion: Concurrent, trough-synchronized 0.75 Hz rTMS combined with tACS may be a reliable protocol to induce long-lasting oscillatory activity in the delta frequency range. The results of the current study might perspectively be relevant for clinical treatment of sleep disturbances which are accompanied by pathologically altered brain oscillations, and enhancement of memory consolidation.