Neural mechanism by which transcranial direct current stimulation reduces cigarette cravings: study protocol for a randomized controlled crossover trial

Background and objectives: Controlling the urge to smoke that stems from a cue-induced craving is the key to successfully breaking the habit. Transcranial direct current stimulation (tDCS) has been shown to improve human control over cognition and behavior. Preliminary behavioral studies have shown that tDCS can reduce cigarette cravings. However, the underlying neural mechanism remains poorly understood. In this study, we used transcranial direct current to stimulate the dorsolateral prefrontal cortex in patients who were addicted to cigarettes. We analyzed the correlation between changes in brain function indicators (e.g., local brain activation and long-distance connectivity) caused by tDCS and the change in cigarette cravings, with the purpose of identifying the neural mechanism by which tDCS to the prefrontal lobe reduces cigarette cravings. Design: A prospective, single-center, randomized, controlled crossover trial. Methods: Forty-two patients addicted to cigarettes who received treatment in the Affiliated Hospital of Anhui Medical University, China received one session each of real and sham tDCS. The time interval between real and sham stimulations was 1 week. The order of stimulation was determined using a random number table. For real tDCS, stimulation intensity was 1 mA, and stimulation time was 30 minutes. For sham tDCS, stimulation intensity was increased to 1 mA within 30 seconds, and then decreased to 0 mA within the next 30 seconds. Stimulation was not performed within the subsequent 29 minutes. At the end of each stimulation session, functional magnetic resonance imaging was performed to record brain activity in patients during a smoking-cue task. Participants reported how much they craved cigarettes using a Visual Analog Scale before and after watching smoking scenes. Outcome measures and results: The primary outcome measure was the degree to which cigarette cravings increased after watching smoking scenes following each stimulation session. The secondary outcome measures were local brain activation and long-distance connectivity between activated brain regions after watching smoking scenes, as well as the incidence of reverse reactions following each stimulation session. After the data collection was complete, data from 32 of the 42 initial patients were included in the final analysis. The results revealed that the increase in cue-induced cigarette cravings was significantly reduced (t = 2.319, df = 31, P = 0.027) after real tDCS compared to sham tDCS. Significant effects were observed in the left superior frontal gyrus and left middle frontal gyrus. Psychophysiological interaction revealed that the connectivity between the dorsolateral prefrontal cortex and the right parahippocampal gyrus was correlated with the amount of increase in cue-induced cigarette cravings (r = 0.522, P = 0.002). Discussion: Based on fMRI findings, the present study was performed to identify the neural mechanism through which tDCS reduces cue-induced cigarette craving. Preliminary results suggest that electrical stimulation to the dorsolateral prefrontal cortex reduces craving by modulating the long-distance coupling associated with the dorsolateral prefrontal cortex. Ethics and dissemination: This study was approved by the Biomedical Ethics Committee, Anhui Medical University, China (approval number: 20140241). The study protocol was performed in strict accordance with the Declaration of Helsinki formulated by the World Medical Association. Written informed consent of the study protocol and procedure was obtained from each patient. Patient recruitment and data collection began in March 2014. Outcome measures were analyzed in February 2015. The trial ended in March 2015. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-IPR-16007980).