REVIEW Neurobiology of the Adolescent Brain and Behavior: Implications for Substance Use Disorders B. J. Casey, Ph.D., AND Rebecca M. Jones, M.S. Objective: Adolescence is a developmental period that entails substantial changes in risk- taking behavior and experimentation with alcohol and drugs. Understanding how the brain is changing during this period relative to childhood and adulthood and how these changes vary across individuals are key in predicting risk for later substance abuse and depen- dence. Method: This review discusses recent human imaging and animal work in the context of an emerging view of adolescence as characterized by a tension between early emerging “bottom-up” systems that express exaggerated reactivity to motivational stimuli and later maturing “top-down” cognitive control regions. Behavioral, clinical, and neurobiological evidences are reported for dissociating these two systems developmentally. The literature on the effects of alcohol and its rewarding properties in the brain is discussed in the context of these two systems. Results: Collectively, these studies show curvilinear development of motivational behavior and the underlying subcortical brain regions, with a peak inflection from 13 to 17 years. In contrast, prefrontal regions, important in top-down regulation of behavior, show a linear pattern of development well into young adulthood that parallels that seen in behavioral studies of impulsivity. Conclusions: The tension or imbalance between these developing systems during adolescence may lead to cognitive control processes being more vulnerable to incentive-based modulation and increased susceptibility to the motiva- tional properties of alcohol and drugs. As such, behavior challenges that require cognitive control in the face of appetitive cues may serve as useful biobehavioral markers for predicting which teens may be at greater risk for alcohol and substance dependence. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(12):1189 –1201. Keywords: adolescence, brain, development, alcohol, risk-taking A dolescence is a transitional period of de- velopment when there are many changes experienced concomitantly, including physical maturation, drive for independence, in- creased salience of social and peer interactions, and brain development. 1-3 This developmental pe- riod is also a time characterized by an inflection in risky behaviors including experimentation with drugs and alcohol, criminal activity, and unprotected sex. Understanding the neural basis of these risky behaviors is key in identifying which teens may be at risk for poor outcomes, such as substance dependence and abuse. Different hypotheses have been postulated for why adolescents may engage in impulsive and risky behaviors. Traditional accounts of adoles- cence suggest that it is a period of development associated with progressively greater efficiency of cognitive control capacities. This efficiency in cognitive control is described as dependent on maturation of the prefrontal cortex as evidenced by imaging 4-7 and postmortem studies 8-10 show- ing continued structural and functional develop- ment of this region well into young adulthood. Improved cognitive control with development of the prefrontal cortex is consistent with a linear increase in this ability from childhood to adult- hood. Yet suboptimal choices and actions ob- served during adolescence represent an in- flection in development 11 that is unique from childhood or adulthood, as evidenced by the National Center for Health Statistics on adoles- cent behavior and mortality. 12 If cognitive control and an immature prefrontal cortex were the basis for suboptimal choice behavior alone, then chil- dren should look remarkably similar or presum- JOURNAL OF THE AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY VOLUME 49 NUMBER 12 DECEMBER 2010 1189 www.jaacap.org