The Role of Executive Functions in Cocaine Abuse

描述（由申请人提供）：在美国和其他地方，可卡因滥用仍然是一个重大的医疗和社会问题。尽管人们对可卡因作用的药理学基础以及药物滥用的环境和社会经济因素的认识日益加深，但对与成瘾有关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认知组成部分是一种失控的执行障碍，也就是说，根据强烈的消费动机，无法控制自己的行为。我们以前的研究已经确定了特定的执行过程及其相应的功能神经解剖学，这些神经解剖学在可卡因使用者中受到损害。具体而言，前扣带回和右背外侧前额叶功能减退已被观察到的反应抑制和错误检测任务的积极可卡因用户。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。提出了一系列的研究，将调查受损的认知控制的功能后果。指导性的假设是，前扣带回，一个参与监测一个人的行为的结构，是可卡因使用者的核心神经生物学缺陷。由于这种结构被认为是启动参与其他前额叶结构中央实施认知控制，我们建议，这些前额叶“赤字”可能是次要的扣带回赤字。拟议研究的另一个主要目的是评估戒毒后认知功能障碍的持续性或改善情况。这项拟议中的研究将评估可卡因使用者在一年禁欲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，自适应控制（即，行为灵活性）和注意力控制（即，能够忽略可卡因刺激）。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通过禁欲改善。

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.