Personalised transcranial alternating current stimulation as a novel therapeutic treatment for post-traumatic stress disorder

Transcranial alternating current stimulation (tACS) is a form of non-invasive brain stimulation that externally applies weak oscillatory electrical currents (typically 1-2mA) at a specified frequency to the brain. tACS can modulate cortical excitability through entrainment and spike-timing dependent plasticity. Entrainment is a primary mechanism proposed to drive the modulatory effects of tACS on cortical excitability and refers to the synchronisation of endogenous brain oscillations to another (external) driving frequency. Entrainment effects can be optimised by matching the tACS frequency to the individual’s dominant endogenous frequency for a particular band of oscillation, in this instance the individual’s endogenous alpha frequency. Electroencephalography (EEG) recordings will be used to determine a subject’s dominant endogenous oscillatory frequency within the alpha band, which will then be used to personalise stimulation frequency for tACS therapy. Administration of tACS will be provided using the Rio transceiver device (eemagine Medical Imaging Solutions GmbH), a mobile device for recording EEG signals combined with transcranial alternating current stimulation (tACS). Controlled electrical current stimulation can be triggered from a software application, via external triggers, or via an internal feature extraction pipeline with minimum latency and jitter. The device has been produced and appropriately tested in the ISO accredited facilities ANT Neuro in Germany. The device delivers a voltage controlled current across stimulation electrodes made of conductive rubber encased in commercially supplied saline soaked sponges and are held in place with a fitted cap. The study will use a cross-over, double blind design. Potential participants will complete an initial pre-screen phone call with a research team member. If deemed eligible, participants will complete a consent and baseline session. Participants will provide demographic information, medical history and complete clinician rated assessments and self-report assessments throughout the study period; including MINI-DSM5, CAPS-5, MINI, PCL-5, AQoL and PHQ. Resting-state electroencephalography (EEG; 64-channels) will be completed prior to the start of each treatment block and at the end of each treatment block (conducted at the ANU). Participants will complete two treatment blocks where they will receive 15 sessions, daily (Monday - Friday) for 3 weeks of personalised alpha-tACS and 15 sessions, daily (Monday - Friday) for 3 weeks of sham-tACS. The EEG data recorded will be used to determine participant's individual alpha frequency (IAF), during active treatment block (alpha-tACS condition) the stimulation frequency will be uploaded onto the device. There will be a 4-week break (minimum 4, maximum 8) between blocks and the order of completion counterbalanced across the participant pool. Resting-state EEG (10 channels) will be recorded for 3 minutes prior to, and following, each treatment session (i.e., daily) to track changes in alpha power and posterior-frontal connectivity across treatment periods. On site: Treatment will be administered by a study researcher. The study researcher will provide clear instructions on where the participant is to be seated and demonstrate how to prepare the tACS-EEG cap and fit it to the participant's head. Administration of tACS and recording with EEG will be automatically triggered while participants complete a series of working memory tasks. Following the completion of the working memory tasks, the study researcher will remove the cap and demonstrate how to clean and care for the equipment, Sessions on site are not limited, participants will be able to attend all sessions on site until competency to carry out at home session is clearly demonstrated. At home: All procedures outlined above will be presented to participants in a way that will teach them how to self-administer treatment at home. The treatment itself is pre-programmed into the device and triggered by participants as they complete a highly guided series of working memory tasks. We will use a checklist to assess competency before participants start treatment at home. The checklist requires researchers to assess and sign off on participants' use of the device on several items pertaining to head and cap preparation, machine preparation and stimulation, steps involved during and post stimulation. The participants will only take home the device for self-administration when they have passed this assessment and feel confident with using the device. When participants are competent and feel comfortable to conduct treatments at home, we can monitor use for several sessions over zoom and be available for troubleshooting, if required. For all active tACS treatment session, a peak-to-peak intensity of 2 mA will be administered for 20 minutes, with a 10 s ramp-up and a 10 s ramp-down every time the stimulation starts and stops. The frequency of the tACS will be matched to the participants dominant alpha frequency measured with EEG at baseline and end of the break period.