An investigation of the effects of α and β-frequency neural entrainment using tACS on phase-aligned TMS-evoked corticospinal excitability

Abstract

Deep brain stimulation [DBS] is an effective treatment for many brain disorders (e.g., Parkinsons disease), has a favourable 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, non-invasive 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). We propose that the efficacy of stimulation might be improved, and the variability of its effects reduced, if stimulation could be synchronised with ongoing brain activity. To investigate this, we used transcranial alternating current stimulation (tACS) to induce entrainment of brain activity at two frequencies (=10 Hz and {beta}=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). Our findings confirm that for -tACS and {beta}-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 -tACS and {beta}-tACS; coinciding with the negative peak (trough) for -tACS and the positive peak (peak) for {beta}-tACS. These findings confirm that aligning non-invasive 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.