Impaired Insight and Drug-Seeking Behavior in Cocaine Addiction: an fMRI Study

吸毒成瘾的特征是从自愿吸毒过渡到越来越习惯性和强迫性的吸毒。因此，上瘾个体的行为，包括寻求毒品的行为，可能在一定程度上受到发生在意识中的动机过程的控制。最近的一项评论确实表明，这种自知力受损可能是吸毒成瘾的一个标志。利用功能磁共振成像(FMRI)，目前的提议试图检查这种假定的自知力缺陷的神经相关性。具体地说，这项建议将探索前脑岛(AI)和前扣带回皮质(ACC)的功能，这两个区域都被认为在洞察力和自我意识方面在可卡因成瘾中发挥关键作用。为了实现这一目标，将采用事件相关fMRI颜色词Stroop任务，这是一种经典的神经心理冲突任务，将为本提案的目的进行修改，以测试对任务相关错误的洞察力。这项改进的fMRI Stroop任务将由三个研究组执行：积极使用可卡因成瘾者(CUD+)、寻求治疗的可卡因成瘾者(CUD-)和健康对照组(HC)。然后，这种fMRI错误洞察数据将被用来预测随后的可卡因相关选择行为。后一个研究部分将通过使用图像查看首选项、概率(PIV-P)任务来完成，该任务检查与可卡因相关的图片的选择与其他愉快、不愉快或中性配价的图片的选择。这一设计将允许测试洞察力受损及其神经基础是否会预测寻求毒品的行为。此外，将从当地治疗设施招募的残疾儿童将在这些设施照常治疗期间每两个月完成一次同样的PIV-P任务。这一前瞻性设计将允许在人类成瘾者通过治疗(计划进行7项后续评估)的过程中，测试他们“潜伏的渴望”(戒酒期间不断增加的复发倾向)的有效性，并进一步确定fMRI洞察力数据是否可以预测其时间进程。如果成功，这项提案的结果可能有助于改变吸毒成瘾者的普遍看法，即表现出抗拒治疗和对立的“否认”。相反，这些结果可能会发现吸毒者患有基于神经的、可能是可接受治疗的洞察力缺陷。

Drug addiction is characterized by a transition from volitional drug use to drug use that is increasingly habitual and compulsive. Thus, behavior among addicted individuals, including drug-seeking behavior, may be partly controlled by motivational processes that occur below conscious awareness. A recent review indeed suggested that such impaired insight may be a hallmark of drug addiction. Using functional magnetic resonance imaging (fMRI), the current proposal seeks to inspect the neural correlates of this putative insight deficit. Specifically, this proposal will explore functioning of the anterior insula (AI) and anterior cingulate cortex (ACC), both posited to play key roles in insight and self-awareness, in cocaine addiction. To accomplish this aim, an event- related fMRI color word Stroop task, a classical neuropsychological conflict task, will be employed, which will be modified for the purposes of this proposal to test for insight into task-related errors. This modified fMRI Stroop task will be performed by three study groups: actively using cocaine addicted individuals (CUD+), treatment- seeking cocaine addicted individuals (CUD-), and healthy control subjects (HC). This fMRI insight-into-errors data will then be used to predict subsequent cocaine-related choice behavior. This latter study component will be accomplished through the use of the Preference for Image Viewing, Probabilistic (PIV-P) task, which examines choice for cocaine-related pictures compared with choice for other pleasant, unpleasant, or neutrally valenced pictures. This design will allow for testing of whether impaired insight and its neural underpinnings predict drug- seeking behavior. In addition, the CUD- individuals, who will be recruited from local treatment facilities, will complete this same PIV-P task bi-monthly during treatment-as-usual at these same facilities. This prospective design will allow for testing of the validity of 'incubated craving' (an escalating propensity for relapse during abstinence) in human addicted individuals as they progress through treatment (seven follow-up assessments are planned), and to further establish whether the fMRI insight data predict its time course. If successful, results of this proposal may help change the prevalent perception of drug addicted individuals as displaying treatment- resistant and oppositional "denial." Instead, these results may identify drug addicted individuals as struggling with a neurally-based, and possibly treatment-amenable, insight deficit.