Immediate and Sustained Decrease in Smoking Urges After Acute Insular Cortex Damage

Introduction: Smoking urges are fundamental aspects of nicotine dependence that contribute significantly to drug use and postquit relapse. Recent evidence has indicated that damage to the insular cortex disrupts smoking behaviors and claims to reduce urges associated with nicotine use, although tools that assess urge have yet to be used to validate these findings. We examined the effect of insular versus non-insular damage on urge using a well-accepted urge scale. Methods: This 3-month observational prospective cohort study consisted of 156 current smokers hospitalized for acute ischemic stroke (38 with insular infarctions, 118 with non-insular infarctions). During hospitalization, the Questionnaire of Smoking Urges (QSU)-brief was assessed retrospectively based on experiences before the stroke (baseline, T0), prospectively immediately following the stroke (T1) and once more via telephone at 3-month follow-up (T2), with higher scores indicating greater urge. Bivariate statistics and multivariable linear regression were used to evaluate differences in QSU-brief scores, relative to baseline, between exposure groups, controlling for age, baseline dependence, stroke severity, use of nicotine replacement, and damage to other mesocorticolimbic regions. Results: A greater reduction in QSU-brief score was seen in the insular group compared to the noninsular group from T0 to T1 (covariate-adjusted difference in means of -1.15, 95% CI: -1.85, -0.44) and similarly from T0 to T2 (covariate-adjusted difference in means of -0.93, 95% CI: -1.79, -0.07). Conclusions: These findings confirm the potential role of the insula in regulating nicotine-induced urges and support the growing evidence of its novelty as a key target for smoking cessation interventions. Implications: Human lesioning studies that evaluate the insula's involvement in maintaining nicotine addiction make inferences of the insula's role in decreasing urge, but do not use validated instruments that directly assess urges. This study corroborates prior findings using the continuous Questionnaire of Smoking Urges to quantify changes in urge from before lesion onset to immediate and 3-month follow-up time points.