- Despite high rates of tobacco use during adolescence, few empirically validated smoking cessation strategies exist for adolescent smokers. Developing an understanding of the neural underpinnings of cognitive control processes in adolescent smokers, and their relationship to quit behaviors, may help advance the development of enhanced behavioral and pharmacological therapies. The current pilot study explored the relationship between brain responses during performance of the Stroop color-word interference task and reduction in tobacco use (as measured by changes in cotinine levels) in treatment-seeking adolescent smokers participating in a high school-based smoking-cessation program. Eleven adolescent daily smokers participated in a prequit session during which neural activity in response to congruent and incongruent events in a Stroop task was examined using functional MRI (fMRI). Changes in urine cotinine levels from prequit baseline to end of treatment were calculated and correlated with brain activity. Adolescents with greater activation in the inferior frontal gyrus, insula, thalamus, and anterior cingulate had greater reductions in cotinine levels. The preliminary observation of a relationship between treatment outcome and neural correlates of cognitive control prior to treatment onset provides insight into individual differences in adolescent brain function that might relate importantly to treatment outcome.