Intermittent theta burst stimulation with synchronised transcranial alternating current stimulation leads to enhanced frontal theta oscillations and a positive shift in emotional bias

Abstract

Abstract Repetitive transcranial magnetic stimulation (rTMS), delivered to left dorsolateral prefrontal cortex, is an FDA-approved, and NICE-recommended, neuromodulation therapy for major depressive disorder (MDD). However, there is considerable inter-individual variability in rate and extent of clinical response, leading to a focus on approaches for optimising its effectiveness. We present findings from a non-patient study evaluating an approach that combines an efficient type of rTMS—“intermittent theta burst stimulation” (iTBS)—with a second neuromodulation technique—“transcranial alternating current stimulation” (tACS). tACS is delivered in synchrony with the iTBS with the intent of optimising the brain state during stimulation. In four separate sessions, we delivered 3 minutes of iTBS+tACS, iTBS+sham, sham+tACS, or double sham. We measured changes from pre- to post-stimulation in brain theta (4–8 Hz) oscillatory activity using electroencephalography, and we measured emotional bias post-stimulation using a well-studied emotion identification task. Theta activity has previously shown relationships with response to rTMS, and emotional bias has been proposed as a marker of potential antidepressant efficacy. We found that frontal theta power was enhanced following the dual therapy, building up over the 15-minute post-stimulation period to exceed that following either stimulation technique alone or double sham. Emotional bias, measured 20 minutes post-stimulation, was also significantly more positive following dual therapy. These findings indicate that tACS-synchronised iTBS (tsiTBS) holds promise as an augmentation approach for rTMS, which awaits validation in multi-session patient studies.