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

描述（由申请人提供）：药物成瘾的特征是从自愿使用药物过渡到日益习惯和强迫的药物使用。因此，成瘾者的行为，包括寻求药物的行为，可能部分地受到发生在意识意识之下的动机过程的控制。最近的一项研究确实表明，这种洞察力受损可能是药物成瘾的一个标志。利用功能性磁共振成像（fMRI），目前的建议试图检查这种假定的洞察力缺陷的神经相关性。具体来说，这项建议将探讨前额叶（AI）和前扣带皮层（ACC）的功能，这两个假设发挥关键作用的洞察力和自我意识，在可卡因成瘾。为了实现这一目标，将采用与事件相关的fMRI颜色词Stroop任务（一种经典的神经心理冲突任务），并将根据本提案的目的对其进行修改，以测试对任务相关错误的洞察。该改良的fMRI Stroop任务将由三个研究组执行：积极使用可卡因成瘾个体（CUD+）、寻求治疗的可卡因成瘾个体（CUD-）和健康对照受试者（HC）。这个fMRI洞察错误的数据将被用来预测随后的可卡因相关的选择行为。后一项研究将通过使用图像观看偏好概率（PIV-P）任务来完成，该任务将检查可卡因相关图片的选择与其他令人愉快、不愉快或中性的图片的选择进行比较。这种设计将允许测试是否受损的洞察力和其神经基础预测药物寻求行为。此外，将从当地治疗机构招募的CUD-个体将在这些相同机构的常规治疗期间每两个月完成一次相同的PIV-P任务。这种前瞻性设计将允许测试人类成瘾个体在治疗过程中的“孵化渴望”（戒断期间复发的升级倾向）的有效性（计划进行七次随访评估），并进一步确定fMRI洞察数据是否预测其时间进程。如果成功的话，这项建议的结果可能有助于改变人们对吸毒成瘾者的普遍看法，即他们表现出对治疗的抗拒和反对性的“否认”。“相反，这些结果可能会确定吸毒成瘾的个人与神经为基础的斗争，并可能治疗，洞察力缺陷。 公共卫生相关性：根据美国卫生与公众服务部的最新报告，在2006年被列为需要药物使用治疗的2110万人中，只有4.5%的人真正认为需要治疗。如果成功的话，这项研究将揭示一个以前未被探索的成瘾者治疗障碍。然后可以使用纵向研究来预测长期治疗结果（例如，几年后持续戒断），可能最终导致实施干预措施，以改善洞察力，从而改善治疗结果。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Only 4.5% of the 21.1 million persons classified in 2006 as needing substance use treatment actually perceived a need for therapy, according to the latest report from the US Department of Health and Human Services. If successful, this study will have uncovered a previously unexplored impediment to treatment in addicted individuals. Longitudinal studies can then be used to predict longer-term treatment outcome (e.g., sustained abstinence after several years) among addicted individuals with compromised insight, perhaps ultimately culminating in the implementation of interventions to improve insight and thus improve treatment outcomes.