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蛋白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，促进与环境问题雅阁的适应，并防止对功能失调的行为模式的持续。依赖可卡因的人群表现出执行控制的赤字，可能会导致他们难以保持禁欲，降低自上而下的控制机制的有效性，以指导适当的目标方向。错误监测的电生理指标已被定位在前扣带回内，并被认为依赖于适当的中脑边缘多巴胺能流到前扣带回。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蛋白可用性增加和/或D2受体结合减少。长期使用可卡因，然后，通过干扰多巴胺介导的监测性能，减弱错误处理。当一个人看到另一个人犯了错误时，就会出现类似的与错误相关的电生理特征。这种与观察者错误相关的消极性（oERN）似乎很适合作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，并可能受到诸如观点采择能力和移情关注水平等特征的影响。低共情的关注可能解释高共病与药物滥用人群中的外化障碍。心智研究网络最近获得了一台最先进的移动的MRI扫描仪，在部署的头两年里，该扫描仪已被用于收集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。这种移动的MRI系统的部署，从而提供了前所未有的访问严重的可卡因滥用者与共病外化特征的人口。有了这个访问，我们建议收集多模态（EEG/fMRI）数据300例被监禁的参与者，分层可卡因滥用和非可卡因滥用组，在性能和观察，去/不去反应抑制任务，旨在引起错误。错误监测的电生理指标将根据脑电位数据计算，而前扣带回的血流动力学活动将根据fMRI数据计算。还将从可卡因依赖性和匹配的健康受试者中采集唾液样本，用于研究多巴胺转运蛋白（SLC 6A 3）和受体（DRD 2和DRD 4）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。通过该项目获得的数据将作为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，这项研究将提供关于可卡因依赖的神经认知和遗传基础的重要信息，并将成为制定未来临床治疗方案的门户。The Mind Research Network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朝着未来专注于治疗和治疗应用的工作迈出的重要一步。

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.