Enhancing prefrontal modulation by phase-locking intermittent theta burst stimulation to a concurrent transcranial alternating current stimulation.

Theta burst stimulation (TBS) modulates cortical excitability by applying bursts of transcranial magnetic stimulation (TMS) in theta rhythms. Individual responses to TBS vary however greatly due to various factors, such as anatomical differences or the phase of the ongoing oscillatory activity in which TBS pulses are applied. To combat this variability, we exploit the ability of transcranial alternating current stimulation (tACS) to shape the state of cortical excitability in a phase-dependent manner. While cortical excitability is increased at crests of the tACS-induced current, applying the TBS triplet pulses at these crests has the potential to produce larger neuronal responses and thus increase the likelihood of LTP. In our randomized sham-controlled study, we focused on enhancing prefrontal cortex excitability by phase-locking intermittent TBS (iTBS) to the crests of an induced 5Hz tACS current. Twenty-seven healthy participants received two iTBS sessions, once paired with sham-tACS and once with active tACS in a cross-over design. We evaluated effects of our stimulation protocol on cortical excitability by comparing TMS-induced activity and resting-state Microstates in the EEG before and after the stimulation as well as between the two sessions. We found significant effect of iTBS on channel-wise, global and oscillatory TMS-induced activity, as well as changes in Microstates. The concurrent, phase-locked tACS-iTBS protocol notably decreased the N100 amplitude of the Global Mean Field Power. We also found that baseline TMS-induced oscillatory activity was a key predictor of changes in TMS-related oscillatory activity. In the case of TMS-related gamma oscillations, a significant interaction between our stimulation protocols and baseline activity was observed, indicating that the relationship between baseline and post-iTBS oscillations was strengthened by the concurrent phase-locked tACS-iTBS stimulation protocol. These findings highlight the potential of phase-locked tACS to enhance the effects of iTBS on prefrontal cortical excitability.