Closed-loop tES-non-invasive Stimulation (CLIBM)

Closed-loop approaches may offer greater efficacy and lower variability across individuals compared to current open-loop stimulation approaches, yet they remain a relatively new approach, with no studies evaluating closed-loop transcranial low-intensity focused ultrasound stimulation (FUS) yet.

For this reason, we will collect and evaluate cognitive, biological and metabolic data from healthy participants, before and after closed-loop and open-loop stimulation interventions. This will allow us to compare our proposed closed-loop stimulation approach to stablished non-invasive techniques and to investigate the underlying mechanisms through which FUS can alter brain activity.

For this study, participants will attend multiple visits. To assess eligibility, participants will attend one initial session in-person before the start of the study.

Following safety guidelines, each participant will receive a maximum of two 1-hour MRI scanning sessions in a single week.

This study will be separated into two blocks of stimulation sessions: one block for tACS-FUS, and another block for TI-FUS. Participants will be randomly allocated to receive one of the blocks.

Before the during recruitment, participants will be asked to complete online some baseline questionnaires such as the O-Life inventory, BECK, MAIA, or STAI. Furthermore, full eligibility will be assessed in person.

At the first appointment, participants will have a brain scan at Sir Peter Mansfield Imaging Centre or Queen's Medical Centre, Nottingham, UK. This will help us to apply the brain stimulation to the right part of the participant's brain, as well as obtain baseline functional, metabolic and structural information.

Participants will be randomly allocated to either receive open-loop FUS (FUS with Sham tES), closed-loop FUS (dual FUS-tES), tES with Sham FUS, or double sham FUS-tES, in the second appointment and the other interventions in the subsequent visits for their assigned block. During all stimulation sessions, we will use an AntNeuro neuronavigation system to guide the location of the transducer.

During either of the stimulation visits, participants will have physiological (EEG) and cognitive markers recorded. Some emotional assessments (i.e., through a short STAI) will be performed before and after stimulation. EEG recordings will be conducted before, during and after stimulation on the same day. Rest-state EEG will be recorded pre-stimulation before the start of the cognitive tasks, and post-stimulation after the end of the cognitive tasks.

The participant will then undergo one cognitive assessment, which will consists on a visual working memory task (delayed-spatial-estimation-task). The task involves visual stimuli, with responses recorded via keyboard. The task is designed to take approximately 5-15 minutes to complete on pre and post-stimulation. The duration of the task during stimulation will be adapted to the duration of the stimulation. Following this, participants will receive the allocated intervention.

Participants will have the same physiological and cognitive assessments recorded during the stimulation and after the stimulation has been completed. For the closed-loop stimulation, participants will also undergo an MRI scanning after the stimulation.

The first visit, consisting of brain scan, will be separated by at least 24 hours from the second visit. Subsequent visits will be separated by at least one week from each other.

During each consecutive appointment, participants will be asked about any changes to their eligibility and continued consent.