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

描述（由申请人提供）：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，成瘾个体的行为，包括寻求药物的行为，可能在一定程度上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吸毒成瘾的标志。使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，本研究将探讨前岛（AI）和前扣带皮层（ACC）在可卡因成瘾中的功能，这两种功能都被认为在洞察力和自我意识中起着关键作用。为了实现这一目标，将采用一个与事件相关的fMRI颜色词Stroop任务，这是一个经典的神经心理冲突任务，将根据本提案的目的进行修改，以测试对任务相关错误的洞察。这项改进的fMRI Stroop任务将由三个研究组进行：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）。这种功能磁共振成像对错误的洞察数据将用于预测随后与可卡因相关的选择行为。后一个研究组成部分将通过使用图像观看偏好，概率（PIV-P）任务来完成，该任务检查与可卡因相关的图像的选择与其他愉快的，不愉快的或中性价值的图像的选择。这个设计将允许测试是否受损的洞察力和它的神经基础预测药物寻求行为。此外，从当地治疗机构招募的CUD个体将在这些相同设施的常规治疗期间每两个月完成相同的PIV-P任务。这种前瞻性设计将允许在人类成瘾个体的治疗过程中测试“孵化渴望”（在戒断期间不断升级的复发倾向）的有效性（计划进行七次后续评估），并进一步确定fMRI洞察数据是否预测其时间进程。如果成功，这一建议的结果可能有助于改变对吸毒成瘾者的普遍看法，即表现出治疗抵抗和对立的“否认”。相反，这些结果可能表明，吸毒成瘾的人正在与一种以神经为基础的、可能是可以治疗的洞察力缺陷作斗争。

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.