The Role of Executive Functions in Cocaine Abuse

描述（由申请人提供）：可卡因滥用在美国和其他地方仍然是一个重大的医疗和社会问题。尽管对可卡因作用的药理学基础以及药物滥用中的环境和社会经济因素的认识不断增加，但对成瘾所涉及的认知因素的关注相对较少。有人提出，人类成瘾的一个重要的认知组成部分是控制的执行障碍，也就是说，由于强烈的消费毒品的动机，无法控制自己的行为。我们之前的研究已经确定了可卡因使用者特定的执行过程及其相应的功能性神经解剖学受损。具体来说，在活跃可卡因使用者的反应抑制和错误检测任务中，已经观察到前扣带和右背外侧前额叶活动减少。由于这些结构是行为认知控制的核心，它们的失调可能导致习惯或环境线索对行为的过度影响。提出了一系列研究，将调查认知控制受损的功能后果。指导性假设是，前扣带是可卡因使用者的核心神经生物学缺陷。前扣带是一种涉及监控个人行为的结构。由于这一结构被认为启动了对认知控制起核心作用的其他前额叶结构的参与，我们提出这些前额叶“缺陷”可能是继发于扣带缺陷。该研究的另一个主要目的是评估戒断药物后认知功能障碍的持续或改善。拟议的研究将评估可卡因使用者在一年戒断期开始和结束时的执行神经功能。任务将包括抑制控制、错误检测、适应性控制（即行为灵活性）和注意力控制（即能够忽略可卡因刺激）的措施。该研究还将评估这些过程中的功能障碍是否预示着复发或随着戒断而改善。

DESCRIPTION (provided by applicant): Cocaine abuse continues to be a substantial medical and social problem in the USA and elsewhere. Despite increasing knowledge of the pharmacological basis of cocaine's effects and of the environmental and socio- economic factors in drug abuse, relatively little attention has been given to the cognitive factors that are involved in addiction. It is proposed that a substantial cognitive component of human addiction is a dysexecutive loss of control, that is, an inability to control one's own behavior in light of the strong motivation to consume drug. Our previous research has identified specific executive processes and their corresponding functional neuroanatomy that are compromised in cocaine users. Specifically, anterior cingulate and right dorsolateral prefrontal hypoactivity have been observed for response inhibition and error detection tasks in active cocaine users. As these structures are central to the cognitive control of behavior, their dysregulation may result in an inordinate influence of habits or environmental cues on behavior. A series of studies are proposed that will investigate the functional consequences of compromised cognitive control. The guiding hypothesis is that the anterior cingulate, a structure involved in monitoring one's behavior, is a core neurobiological deficit in cocaine users. As this structure is thought to initiate the involvement of other prefrontal structures central to implementing cognitive control, we propose that these prefrontal "deficits" may be secondary to the cingulate deficit. A further major aim of the proposed research is to assess the persistence or amelioration of cognitive dysfunctions following drug abstinence. The proposed research will assess the executive neurofunctioning of cocaine users at the start and end of a one-year period of abstinence. Tasks will include measures of inhibitory control, error detection, adaptive control (i.e., behavioral flexibility) and attentional control (i.e., being able to ignore cocaine stimuli). The research will also assess if dysfunction in these processes is predictive of relapse or ameliorates with abstinence.