Transcranial Magnetic Stimulation for Reducing the Relative Reinforcing Value of Food in Adult Patients With Obesity Pursuing Metabolic and Bariatric Surgery: Protocol for a Pilot, Within-Participants, Sham-Controlled Trial.

Background: Metabolic and bariatric surgery (MBS) is the most effective and durable obesity treatment. However, there is heterogeneity in weight outcomes, which is partially attributed to variability in appetite and eating regulation. Patients with a strong desire to eat in response to the reward of palatable foods are more likely to overeat and experience suboptimal outcomes. This subgroup, classified as at risk, may benefit from repetitive transcranial magnetic stimulation (rTMS), a noninvasive brain stimulation technique that shows promise for reducing cravings and consumption of addictive drugs and food; no study has evaluated how rTMS affects the reinforcing value of food and brain reward processing in the context of MBS.

Objective: The goal of the Transcranial Magnetic Stimulation to Reduce the Relative Reinforcing Value of Food (RESTRAIN) study is to perform an initial rTMS test on the relative reinforcing value (RRV) of food (the reinforcing value of palatable food compared with money) among adult patients who are pursuing MBS and report high food reinforcement. Using a within-participants sham-controlled crossover design, we will compare the active and sham rTMS conditions on pre- to posttest changes in the RRV of food (primary objective) and the neural modulation of reward, measured via electroencephalography (EEG; secondary objective). We hypothesize that participants will show larger decreases in food reinforcement and increases in brain reward processing after active versus sham rTMS.

Methods: Participants (n=10) will attend 2 study sessions separated by a washout period. They will be randomized to active rTMS on 1 day and sham rTMS on the other day using a counterbalanced schedule. For both sessions, participants will arrive fasted in the morning and consume a standardized breakfast before being assessed on the RRV of food and reward tasks via EEG before and after rTMS of the left dorsolateral prefrontal cortex.

Results: Recruitment and data collection began in December 2022. As of October 2023, overall, 52 patients have been screened; 36 (69%) screened eligible, and 17 (47%) were enrolled. Of these 17 patients, 3 (18%) were excluded before rTMS, 5 (29%) withdrew, 4 (24%) are in the process of completing the protocol, and 5 (29%) completed the protocol.

Conclusions: The RESTRAIN study is the first to test whether rTMS can target neural reward circuits to reduce behavioral (RRV) and neural (EEG) measures of food reward in patients who are pursuing MBS. If successful, the results would provide a rationale for a fully powered trial to examine whether rTMS-related changes in food reinforcement translate into healthier eating patterns and improved MBS outcomes. If the results do not support our hypotheses, we will continue this line of research to evaluate whether additional rTMS sessions and pulses as well as different stimulation locations produce clinically meaningful changes in food reinforcement.

Trial Registration: ClinicalTrials.gov NCT05522803; https://clinicaltrials.gov/study/NCT05522803.

International Registered Report Identifier (irrid): DERR1-10.2196/50714.