Differential effects of left and right insula inhibition on craving and cognitive control in regular smokers

Background

There is an urgent need for the development of more effective treatment strategies for smoking cessation. The insula is a brain region involved in several addiction-related processes including craving and cognitive control, but these functions appear to be lateralized. Based on lesion studies it has been suggested that inhibition, rather than stimulation, of the insula may have therapeutic potential in the treatment of addiction. Continuous theta burst stimulation (cTBS), a form of transcranial magnetic stimulation (TMS), can result in the inhibition of neuronal activity and can be targeted at the insula with the use of an innovative H8 TMS coil. This project will, for the first time, compare the role of left and right insular cortices in craving and cognitive control in regular smokers by investigating differential effects of deep cTBS of left or right insular cortices. It is expected that, compared to sham stimulation, deep cTBS of the left insula affects cue-induced craving, whereas cTBS of the right insula is expected to affect cognitive control.

Methods

This study contains a single-blind randomized sham-controlled trial, using a single-session, mixed factorial, cross-over design. Fifty-four regular smokers (50/50 m/f) aged 18-30 will be randomized to undergo sham and active cTBS of the left or the right insula using a H8 TMS coil. Craving and cognitive control will be assessed after both stimulation conditions by a cue exposure task and a stop signal task, respectively, presented in counterbalanced order. 

Results

Twenty participants were included in this study so far, with a mean age of 22.8 (SD=2.6) and 55% women. These participants have been smoking for an average of 6.5 (SD=3.5) years, smoke 15.5 (SD=4.6) cigarettes per day and had a Fagerström Test for Nicotine Dependence (FTND) score of 4.8 (SD=1.8). Baseline self-reported cigarette craving, measured with a 7-point VAS-scale, was 4.8(1.8) and baseline self-reported impulsivity, measured with the Barrat Impulsiveness Scale (BIS-11), was 65.3 (SD=11.2). As the order of stimulation type (i.e. first active or first sham stimulation) is concealed until the study is completed, it is not possible to analyze the effects of insula inhibition on craving and cognitive control at this moment. However, these will be presented during the conference. 

Conclusions

The results of this study will contribute to the current body of knowledge on functional lateralization of the insula regarding addiction-related processes. Although inhibition of the insula has been suggested to have therapeutic potential, inhibitory effects on craving and cognitive control have not been assessed so far. The coil used in this study is not commercially available as of yet, making this project a frontrunner in the field of non-invasive brain stimulation. The results of this study will contribute to the development of more effective TMS protocols for the treatment of smoking based on individual neurocognitive deviations.