Combined transcranial alternating current stimulation and cTBS: a novel approach for neuroplasticity induction

Non-invasive brain stimulation can induce functionally relevant plasticity in the human cortex. While there is great potential for these protocols to be used therapeutically in a range of neurological and psychiatric disorders, clinical applicability is currently limited by high inter-individual variability. One factor that might contribute to this variability is the level of cortical inhibition at the time of stimulation. The alpha rhythm (8–13 Hz) recorded with electroencephalography (EEG) is thought to reflect pulsatile cortical inhibition; therefore, targeting NIBS to particular phases of the alpha rhythm may provide an approach to enhance plasticity induction. Transcranial alternating current stimulation (tACS) has been shown to entrain cortical oscillations in a frequency-specific manner. We investigated whether the neuroplastic response to continuous theta burst stimulation (cTBS) was enhanced by timing bursts of stimuli to the peak or the trough of a tACS-imposed alpha rhythm. While motor evoked potentials (MEPs) were unaffected when cTBS was applied in-phase with the peak of the tACS-imposed oscillation, cTBS applied in-phase with the trough induced greater MEP depression compared with cTBS applied during a sham tACS protocol. This enhanced MEP depression was dependent on the individual peak frequency of the endogenous alpha rhythm recorded with EEG prior to stimulation, and was strongest in those participants classified as non-responders to standard cTBS. These findings suggest that tACS may be used in combination with cTBS to enhance the plasticity response. Furthermore, the peak frequency of endogenous alpha, as measured with EEG, may be used as a simple marker to pre-select those individuals likely to benefit from this approach.