Adolescent Brain Development and Effects of Drug Abuse

描述（由申请方提供）：本提案的总体目标是（i）使用结构神经成像和神经认知评估扩展典型发育青少年样本中前额叶皮层（PFC）神经发育的研究计划，以及（ii）在探索性研究中将此知识应用于年龄匹配的吸入剂滥用者。前额叶皮层的主要功能之一是对行为进行控制，以便一个人能够追求未来的目标。当享乐信号与这些目标相冲突时，就越来越需要努力控制。在青春期，奖赏的享乐信号可能特别强烈，在PFC成熟之前可能很难克服。我们假设PFC在情绪挑战情况下控制行为的能力在青春期后期仍在发展，使青少年容易受到情绪冲动的影响，其中之一可能是吸毒。现有的工具不仅使我们能够使用神经认知任务评估PFC发育的行为轨迹，而且还可以量化代表大脑结构连接的白色物质成熟的各个方面。本研究将着重于PFC的背外侧与腹内侧区域的发展。通过横断面和纵向研究，将使用行为和成像工具来量化非药物使用对照青少年与滥用吸入性药物的临床参考样本中PFC介导的行为和白色物质的发展。将入组并前瞻性随访每份样本。该设计允许对行为和大脑成熟的正常年龄相关变化进行横断面检查，通过纵向评估在受试者内验证这些发现，并将吸入性药物滥用者与对照组的大脑发育进行组内和组间比较。

DESCRIPTION (provided by applicant): The general goals of this proposal are (i) to use structural neuroimaging and neurocognitive assessments to expand upon a program of research on the neurodevelopment of the prefrontal cortex (PFC) in a sample of typically developing adolescents and (ii) to apply this knowledge to age-matched inhalant abusers in an exploratory study. One of the main functions of the PFC is to exert control over behavior so that a person can pursue future goals. Effortful control is increasingly demanded when hedonic signals conflict with these goals. Hedonic signals of reward may be especially strong during adolescence and may be difficult to overcome prior to PFC maturation. We hypothesize that the PFC's ability to control behavior under emotionally challenging situations is still developing very late in adolescence rendering teens vulnerable to their emotional impulses, one of which may be to engage in drug use. Tools now exist that allow us not only to assess the behavioral trajectory of PFC development using neurocognitive tasks but also to quantify aspects of white matter maturation that represent connectivity across brain structures. This study will focus on the development of the PFC's dorsolateral versus ventromedial regions. Through cross-sectional and longitudinal investigations, behavioral and imaging tools will be used to quantify the development of PFC-mediated behaviors and white matter "naturation in adolescents who are non-drug using controls versus a clinic-referred sample who abuse inhalant drugs. Each sample will be enrolled and prospectively followed. This design permits a cross-sectional examination of normal age-related changes in behavioral and brain maturation, validation of these findings within-subjects through longitudinal assessment, and within-and between-group comparisons of brain development in inhalant abusers versus controls.