Adolescence is a period of heightened vulnerability both to addictive behaviors and drug-induced brain damage. Yet, only limited information exists on the brain mechanisms underlying these adolescent-specific characteristics. Moreover, distinctions in brain correlates between predisposition to drug use and effects of drugs in adolescents are unclear. Using cortical thickness and diffusion tensor image analyses, we found greater and more widespread gray and white matter alterations, particularly affecting the frontostriatal system, in adolescent methamphetamine (MA) users compared with adult users. Among adolescent-specific gray matter alterations related to MA use, smaller cortical thickness in the orbitofrontal cortex was associated with family history of drug use. Our findings highlight that the adolescent brain, which undergoes active myelination and maturation, is more vulnerable to MA-related alterations than the adult brain. Furthermore, MA-use-related executive dysfunction was greater in adolescent MA users than in adult users. These findings may provide explanation for the severe behavioral complications and relapses that are common in adolescent-onset drug addiction. Additionally, these results may provide insights into distinguishing the neural mechanisms that underlie the predisposition to drug addiction from effects of drugs in adolescents.

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Funding Acknowledgements Type of funding sources: None. Introduction Rhythm control is a therapeutic approach to restore sinus rhythm from atrial fibrillation (AF). Current studies have demonstrated efficacy of rhythm control with radiofrequency catheter ablation (RFCA) for survival, however there is lack of data regarding the long term outcome of patients who refused RFCA. Purpose This study was aimed to compare outcomes, consist of death and stroke, in patients who refused RFCA. Method Patients with AF who had been proposed for RFCA but refused and also any rhythm control strategy were enrolled. The primary outcome was all cause death and incidence of stroke, compared with patients with AF who had been treated with RFCA. Results A total 174 patients who refused AF, 175 patients treated with RFCA were enrolled. Median follow up duration was 1125.1 ± 799.0 days. Of refused AF group, 39 (22.3%) were paroxysmal AF at the time of diagnosis. During follow-up, 9 patients in refused RFCA and 11 patients treated with RFCA group had died (4.1% vs 6.1%, p=0.3 by log rank test). Incidence of stroke was significantly higher in patients who refused RFCA, compared with RFCA group (12.0% vs 1.1% , p =0.001 by log-rank test). Cox Regression model showed refusing RFCA was an independent risk factor for the incidence of stroke (Hazard ratio 6.7, 95% Confidence Interval 1.48 – 30.3, p=0.013). Conclusion In AF patient who had refused rhythm control, incidence of stroke was significantly higher in patients who refused RFCA and rhythm control, compared with who had been treated with RFCA. There was no difference in all-cause mortality between two groups.