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

描述(由申请人提供)：本研究的目的是描述可卡因依赖者自我和他人行为监测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之间的关系。监督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，并防止对功能失调的行动模式的执着。可卡因依赖人群表现出执行控制缺陷，这可能是他们难以保持戒烟的根本原因，因为这降低了自上而下指导适当目标方向的控制机制的有效性。错误监测的电生理指标已定位于前扣带回，并被认为依赖于适当的中脑边缘多巴胺能流向前扣带回。长期使用可卡因与前扣带回多巴胺能张力降低有关，可能是由于多巴胺转运体可获得性增加和/或D2受体结合减少。因此，长期使用可卡因可能会干扰多巴胺介导的监测性能，从而削弱错误处理。当一个人看到另一个人犯了错误时，也有类似的与错误相关的电生理特征被记录下来。这种观察者错误相关的消极(OERN)似乎处于很好的位置，可以作为移情关注的潜在指标。反过来，监控他人行为的能力可以作为观察性学习的基础，并可能受到诸如视角选择能力和移情关怀水平等特征的影响。较低的同理心可能解释了吸毒人群中高共患率与外化障碍的原因。精神研究网络最近购买了一台最先进的移动核磁共振扫描仪，在部署的头两年里，它已经被用来收集700多名囚犯的大脑成像数据。临床数据显示，超过65%的囚犯患有严重的药物滥用问题。因此，这一移动核磁共振系统的部署为具有共同外化特征的严重可卡因滥用者提供了前所未有的机会。通过这种访问，我们建议收集300名被监禁参与者的多模式(EEG/fMRI)数据，这些参与者被分成可卡因滥用组和非可卡因滥用组，在执行和观察旨在引发错误的GO/NO-GO反应抑制任务期间。错误监测的电生理指标将根据脑电位数据计算，而来自前扣带回的血液动力学活动将根据fMRI数据计算。还将收集可卡因依赖和匹配的健康参与者的唾液样本，以调查多巴胺转运体(SLC6A3)和受体(DRD2和DRD4)的基因类型。通过分析头发和尿液样本，将使用6个月、12个月、18个月和24个月的随访预约来评估复发。通过该项目获得的数据将成为对严重可卡因滥用者样本中认知和情感异常进行的最大规模和最全面的调查，并首次对这些认知/情感异常与多巴胺能多态之间的关系进行重大调查。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，并将成为开发未来临床治疗方案的门户。心智研究网络的最终使命是为严重的心理和精神障碍开发新的治疗方案，我们小组设想从这项研究中收集的数据是迈向未来专注于这些研究和治疗应用的重要一步。

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.