External induction and stabilization of brain oscillations in the human

Brain Stimul. May-Jun 2021;14(3):579-587. doi: 10.1016/j.brs.2021.03.011. Epub 2021 Mar 26.


Background: Neural oscillations in the cerebral cortex are associated with a range of cognitive processes and neuropsychiatric disorders. However, non-invasively modulating oscillatory activity remains technically challenging, due to limited strength, duration, or non-synchronization of stimulation waveforms with endogenous rhythms.

Objective: We hypothesized that applying controllable phase-synchronized repetitive transcranial magnetic stimulation pulses (rTMS) with alternating currents (tACS) may induce and stabilize neuro-oscillatory resting-state activity at targeted frequencies.

Methods: Using a novel circuit to precisely synchronize rTMS pulses with phase of tACS, we empirically tested whether combined, 10-Hz prefrontal bilateral stimulation could induce and stabilize 10-Hz oscillations in the bilateral prefrontal cortex (PFC). 25 healthy participants took part in a repeated-measures design. Whole-brain resting-state EEG in eyes-open (EO) and eyes-closed (EC) was recorded before (baseline), immediately (1-min), and 15- and 30-min after stimulation. Bilateral, phase-synchronized rTMS aligned to the positive tACS peak was compared with rTMS at tACS trough, with bilateral tACS or rTMS on its own, and to sham.

Results: 10-Hz resting-state PFC power increased significantly with peak-synchronized rTMS + tACS (EO: 44.64%, EC: 46.30%, p < 0.05) compared to each stimulation protocol on its own, and sham, with effects spanning between prefrontal and parietal regions and sustaining throughout 30-min. No effects were observed with the sham protocol. Moreover, rTMS timed to the negative tACS trough did not induce local or global changes in oscillations.

Conclusion: Phase-synchronizing rTMS with tACS may be a viable approach for inducing and stabilizing neuro-oscillatory activity, particularly in scenarios where endogenous oscillatory tone is attenuated, such as disorders of consciousness or major depression.

Keywords: Alpha; EEG; Electroencephalography; Neuromodulation; Oscillations; Prefrontal cortex; TMS; Transcranial alternating current stimulation; Transcranial magnetic stimulation; tACS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain
  • Electroencephalography
  • Humans
  • Prefrontal Cortex
  • Transcranial Direct Current Stimulation*
  • Transcranial Magnetic Stimulation