Action Monitoring, Action Observation and Dopamine Genes as Predictors of Substan

描述（由申请人提供）：本研究的目的是表征可卡因依赖个体中监测自己和他人行为的神经过程的完整性，并探索这些过程的功能与多巴胺转运体和受体多态性之间的关系。监控自己行为的能力是执行控制的核心组成部分，促进适应环境问题，防止在功能失调的行动模式上坚持不懈。可卡因依赖人群表现出执行控制方面的缺陷，这可能会降低自上而下的控制机制引导适当目标方向的效力，从而导致他们难以保持戒断。错误监测的电生理指标已经定位于前扣带，并被认为依赖于适当的中边缘多巴胺能流到前扣带。长期使用可卡因与前扣带多巴胺能张力降低有关，可能是由于多巴胺转运体可用性增加和/或D2受体结合减少。因此，长期使用可卡因可能通过干扰多巴胺介导的监测表现来减弱错误处理。当一个人看到另一个人犯错误时，也会出现类似的与错误相关的电生理信号。这种观察者错误相关的消极性（oERN）似乎很好地定位为共情关注的潜在指标。反过来，监控他人行为的能力可以作为观察学习的基础，并可能受到换位思考能力和共情关注水平等特征的影响。低共情关注可以解释药物滥用人群中外化障碍的高合并症。心智研究网络最近获得了一台最先进的移动核磁共振扫描仪，在部署的头两年里，它已被用来收集700多名囚犯的大脑成像数据。临床数据表明，超过65%的囚犯有严重的药物滥用问题。因此，这种移动MRI系统的部署为具有合并症外化特征的严重可卡因滥用者提供了前所未有的机会。在此基础上，我们收集了300名被监禁的参与者的多模态（EEG/fMRI）数据，这些参与者被分为可卡因滥用组和非可卡因滥用组，在执行和观察一个旨在引发错误的“去/不去”反应抑制任务期间。误差监测的电生理指标将从脑电位数据中计算，而来自前扣带的血流动力学活动将从功能磁共振成像数据中计算。还将收集可卡因依赖和匹配的健康参与者的唾液样本，以研究多巴胺转运体（SLC6A3）和受体（DRD2和DRD4）基因型。6个月、12- 18个月和24个月的随访将通过分析头发和尿液样本来评估复发情况。通过该项目获得的数据将作为对严重可卡因滥用者样本中认知和情感异常的最大和最全面的调查，以及对这些认知/情感异常与多巴胺能多态性之间关系的第一次重大调查。因此，这项研究将提供有关可卡因依赖的神经认知和遗传基础的重要信息，并将作为未来临床治疗方案发展的门户。心智研究网络的终极使命是为严重的心理和精神障碍开发新的治疗方案，我们的团队设想从这项研究中收集的数据是迈向未来治疗和治疗应用工作的重要一步。

DESCRIPTION (provided by applicant): The purpose of the present study is to characterize the integrity of neural processes underlying the monitoring of one's own and another's behavior within cocaine-dependent individuals, and to explore the relationship between the functionality of these processes and dopamine transporter and receptor polymorphisms. The ability to monitor one's own behavior serves as a central component of executive control, promoting adaptation in accord with environmental concerns, and preventing perseveration on dysfunctional action patterns. Cocaine dependent populations show deficits in executive control that may underlie their difficulty remaining abstinent by reducing the efficacy of top-down control mechanisms to guide appropriate goal-direction. Electrophysiological indicators of error monitoring have been localized within the anterior cingulate and are believed reliant on appropriate mesolimbic dopaminergic flow to the anterior cingulate. Chronic cocaine use has been linked to reduced dopaminergic tone in the anterior cingulate, potentially due to increased dopamine transporter availability and/or reduced D2 receptor binding. Chronic cocaine use may, then, attenuate error processing by interfering with dopamine-mediated monitoring performance. A similar error-related electrophysiological signature has been documented that occurs when one views another person make a mistake. This observer error-related negativity (oERN) appears well positioned to act as an underlying indicator of empathic concern. The ability to monitor another's behavior, in turn, may serve as the basis for observational learning, and may be influenced by characteristics such as perspective-taking ability and level of empathic concern. Low empathic concern may explain the high comorbidity with externalizing disorders within drug-abusing populations. The Mind Research Network has recently acquired a state-of-the-art mobile MRI scanner, which has been used to collect brain imaging data from over 700 inmates in the first two years of deployment. Clinical data indicates that over 65% of inmates suffer from serious substance abuse issues. The deployment of this mobile MRI system thus provides unprecedented access to a population of serious cocaine abusers with comorbid externalizing characteristics. With this access, we propose to collect multimodal (EEG/fMRI) data on 300 incarcerated participants, stratified into cocaine-abusing and non-cocaine-abuse groups, during performance of, and the observation of, a go/no-go response-inhibition task designed to elicit errors. Electrophysiological indicators of error monitoring will be computed from brain potential data, while hemodynamic activity from the anterior cingulate will be computed from the fMRI data. Saliva samples will also be collected from cocaine-dependent and matched healthy participants for investigation of dopamine transporter (SLC6A3) and receptor (DRD2 and DRD4) genotypes. Six-, 12- 18- and 24-month follow-up appointments will be used to evaluate relapse through analysis of hair and urine samples. The data obtained through this project will serve as the largest and most comprehensive investigation of cognitive and affective abnormalities within a sample of serious cocaine abusers, and the first major investigation into the relationship between these cognitive/affective abnormalities and dopaminergic polymorphisms. The research will thus provide important information regarding the neurocognitive and genetic underpinnings of cocaine dependency, and will serve as a gateway towards the development of future clinical treatment protocols. The ultimate mission of The Mind Research Network is the development of novel treatment programs for serious psychological and mental disorders, and our group envisions the data collected from this research as an important step towards future work focused on therepeutic and treatment applications.