Insular Cortex Damage from Stroke and Disruption of Nicotine Dependence : The MINDS Study

Abstract

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Public Health Sciences, 2015.Current pharmacotherapies for treating smoking dependence have profuse side effects and relatively high rates of relapse, and primarily target the brains’ mesocorticolimbic “reward” pathway. Recent evidence suggests that the insular cortex, a central cerebral hemispheric region not part of the mesocorticolimbic structure, may also play an important role in cognitive and emotional processes that facilitate drug use. We hypothesized that current cigarette smokers admitted for ischemic stroke in the insula would demonstrate less severe withdrawal symptoms during admission, greater reduction in smoking-related urges, and a higher likelihood of quitting compared to patients admitted for non-insular strokes. A total of 156 smokers (38 insula and 118 non-insula strokes verified by 3 neuroradiologists using CT and MRI) were recruited from 3 acute care stroke units in Rochester, NY. Validated questionnaires were administered during admission to assess urge (Questionnaire on Smoking Urges, QSU) before and after the stroke as well as withdrawal intensity after stroke (Wisconsin Smoking Withdrawal Scale, WSWS). Continuous abstinence was assessed at 3 months post-discharge. Bivariate statistics and multivariable linear regression were used to evaluate differences in withdrawal, urge, and cessation between insular and non-insular groups, controlling for age, baseline nicotine dependence, stroke severity, nicotine replacement use during admission, pre-stroke intent to quit and damage to other regions in the reward pathway. On average, smokers with insular lesions had a lower WSWS score during admission compared to those with non-insular lesions (adjusted β=-3.12, 95% CI: -4.97, -1.27). Insular damaged participants also had a greater decrease in urges from baseline to hospitalization (adjusted β=-1.15, 95% CI: -1.85, -0.44) and 3 months post-stroke (adjusted β=-0.93, 95% CI: -1.79, -0.07) relative to the non-insular group. The insular damaged group had 2.45 times the odds (95% CI: 0.93, 6.49) of continuous abstinence at follow-up and a reduced instantaneous risk of relapse (HR=0.48, 95% CI: 0.24, 0.98) relative to the non-insular group. Among the quitters, insular damage was associated with higher relative odds of experiencing a disruption of addiction compared to non-insular damage (OR=5.60, 95% CI: 1.52, 20.56). These findings support the potential role of the insula in the mechanism responsible for maintaining addictive behaviors