Altered controllability of functional brain networks among electronic cigarettes users with nicotine dependence

In recent years, the prevalence of electronic cigarettes (e-cigs) use has continued to rise, particularly among youth populations. However, the long-term effects of e-cigs use on brain functional activity remain unclear.

Resting-state functional brain controllability metrics, including average controllability and modal controllability, were computed and compared at the network level between 93 nicotine-dependent e-cigs users and 96 demographically-matched healthy controls. Spearman correlation analyses were implemented to assess the relationships between controllability and various e-cigs use characteristics, including duration of use, frequency patterns, and dependence severity measures.

Compared with healthy controls, e-cigs users exhibited increased average controllability in the right middle frontal gyrus, inferior frontal gyrus, insula, and thalamus (P < .001, false discovery rate corrected), along with increased modal controllability in the left medioventral occipital cortex (P < .001, false discovery rate corrected). Additionally, controllability in subcortical and visual network regions showed a negative correlation with e-cigs use characteristics and sleep quality.

This study is the first to apply network control theory and reveals significant alterations in the average controllability of the right middle frontal gyrus, middle frontal gyrus, inferior frontal gyrus, insula, thalamus and the left insula, as well as in the modal controllability of the left medioventral occipital cortex among nicotine-dependent e-cigs users, indicating impaired brain state transition function. Furthermore, these alterations in brain network properties show negative correlations with both the duration of e-cigs use and sleep quality, suggesting potential behavioral and clinical relevance. These changes may serve as potential biomarkers for future research exploring related intervention strategies.This trial is registered with clinicaltrials.gov (NCT05788068).

Our study identified brain regions that may represent potential neuroimaging features of nicotine-dependent e-cigs users. Furthermore, our findings suggest a new hypothesis for targeted intervention. Key nodes identified-such as the right IFG and INS-warrant further investigation as potential targets for neuromodulation techniques. Future interventional trials are needed to verify whether modulating activity in these brain areas can restore normal control functions and aid smoking cessation, which may pave the way for personalized treatment strategies.