Personalised combined transcranial magnetic and electrical stimulation in healthy adults

In a randomised, single-blind, crossover design, participants will complete three experimental sessions, with at least 5 days between sessions. During each session, participants will receive one of three stimulation conditions: (1) individualised-frequency phase-synchronised intermittent theta burst stimulation combined with transcranial alternating current stimulation (iTBS-tACS), (2) fixed-frequency phase-synchronised iTBS-tACS, or (3) sham iTBS-tACS. iTBS-tACS is a non-invasive brain stimulation intervention that combines transcranial magnetic and electrical stimulation to modulate brain activity. iTBS will be delivered using a Neuro-MS/D TMS device (Neurosoft, Russia) with a cooled figure-of-eight coil. tACS will be delivered via a RIO Transceiver system (eemagine Medical Imaging Solutions GmbH, Germany). Stimulation will be delivered over the left dorsolateral prefrontal cortex (DLPFC). iTBS (600 pulses per session) will be delivered at 80% of resting motor threshold. tACS will be delivered at an intensity of up to 1-2 mA (peak-to-peak). In both active conditions, iTBS and tACS will be delivered in a phase-synchronised manner to maintain a predefined phase relationship between the two forms of stimulation. Each session will consist of a single stimulation lasting approximately 4 minutes. Frequency/duration of intervention: 1 × 4-minute stimulation session per visit, across 3 visits in total (one session under each of the three stimulation conditions), with a minimum of 5 days between visits. In the fixed-frequency condition, stimulation will be delivered using conventional frequencies of 5 Hz (theta) and 50 Hz (gamma). In the individualised-frequency condition, theta and gamma stimulation frequencies will be determined based on oscillatory activity recorded by electroencephalography (EEG) during a working memory task prior stimulation. This individualisation is based on evidence suggesting that matching stimulation frequencies with endogenous neural oscillations may improve neuromodulatory efficacy. The intervention will be delivered face-to-face on an individual basis by trained research team experienced in non-invasive brain stimulation. All study procedures will be conducted at John Curtin School of Medical Research, Australian National University, Canberra, Australia. The intervention will be delivered face-to-face on an individual basis by trained research team experienced in non-invasive brain stimulation. All study procedures will be conducted at John Curtin School of Medical Research, The Australian National University, Canberra, Australia. Attendance will be recorded for all study visits. Stimulation parameters will be documented by the research team during each session. Participants will receive reminders prior to each visit to support adherence.