ABSTRACT Purpose Deep brain stimulation (DBS) is an effective treatment for many brain disorders (e.g., Parkinson's disease), has a favorable adverse effect profile, and can be particularly effective for individuals with treatment‐resistant symptoms. DBS is, however, inaccessible for most individuals, is extremely expensive, and is not considered suitable for children and adolescents. For these reasons, noninvasive alternatives to DBS, such as transcranial magnetic stimulation (TMS), are increasingly being sought to treat brain health conditions. Unfortunately, current TMS approaches exhibit large intra‐ and inter‐subject variability in their efficacy, which limits their use clinically. One likely reason for this is that TMS is invariably delivered without reference to ongoing brain activity (i.e., open loop). Methods We propose that the efficacy of stimulation might be improved, and the variability of its effects reduced, if stimulation could be synchronized with ongoing brain activity. To investigate this, we used transcranial alternating current stimulation (tACS) to induce entrainment of brain activity at two frequencies ( α = 10 Hz and β = 20 Hz), and we delivered single‐pulse TMS that was temporally aligned with the phase of each tACS oscillation. To investigate the effects of tACS‐phase‐aligned TMS, we measured motor‐evoked potentials (MEPs). Findings Our findings confirm that for α‐ and β‐tACS, both corticospinal excitability and inter‐trial variability varied as a function of tACS phase. Importantly, however, the tACS phase angle that produced maximum TMS‐evoked excitability was different for α‐ and β‐tACS, coinciding with the negative peak (trough) for α‐tACS and the positive peak (peak) for β‐tACS. Conclusion These findings confirm that aligning noninvasive brain stimulation to ongoing brain activity may increase the efficacy of TMS and reduce the variability of its effects. However, our results illustrate that the optimal phase of the tACS cycle at which to deliver TMS may vary for different tACS frequencies.
Gialopsou et al. (Tue,) studied this question.