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

行为监测、行为观察和多巴胺基因作为物质的预测因子

• 批准号: 8248788
• 负责人: KENT A KIEHL
• 金额: $ 57.66万
• 依托单位: THE MIND RESEARCH NETWORK
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8248788
• 关键词: Abstinence; Address; Affective; Alcohol abuse; Alcohol or Other Drugs use; Alleles; Anterior; Appointment; Attenuated; Behavior; Behavioral; Brain; Brain imaging; Characteristics; Chronic; Clinical Data; Clinical Research; Clinical Treatment; Cocaine; Cocaine Abuse; Cocaine Dependence; Cognitive; Commit; Comorbidity; DRD2 gene; DRD4 gene; Data; Decision Making; Dependency; Deterioration; Development; Disease; Dopamine; Dopamine D2 Receptor; Dopamine Receptor; Drug Addiction; Drug Monitoring; Drug abuse; Drug usage; Electrophysiology (science); Failure; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Future; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Techniques; Genomics; Genotype; Goals; Hair; Health; Image; Imaging Techniques; Imprisonment; Individual; Investigation; Laboratories; Learning; Link; Magnetic Resonance Imaging; Mediating; Mental disorders; Methods; Midbrain structure; Mind-Body Method; Mission; Molecular Genetics; Monitor; Multimodal Imaging; Nature; Neurobiology; Neurocognitive; Participant; Patients; Pattern; Performance; Persons; Pharmaceutical Preparations; Population; Positioning Attribute; Prevention program; Prisons; Process; Regression Analysis; Relapse; Relative (related person); Reporting; Research; Resolution; Rewards; Risk; Risk Behaviors; Role; Saliva; Sampling; Sex Behavior; Sexually Transmitted Diseases; Substance abuse problem; System; Techniques; Testing; Time; Treatment Protocols; Undifferentiated; Urine; Use of New Techniques; Variant; Work; addiction; anti social; base; cocaine use; cognitive control; criminal behavior; design; dopamine transporter; drug abuser; drug relapse; executive function; experience; follow-up; hemodynamics; high risk; insight; meetings; member; neural circuit; neuroimaging; novel; prevent; psychologic; psychopathic behavior; psychopathic personality; receptor; receptor binding; recidivism; relating to nervous system; response; substance abuser; success; tool; transmission process; treatment program; willingness

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.

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，并探讨这些过程的功能与多巴胺转运蛋白之间的关系和受体多态性。监控自己行为的能力是执行控制的核心组成部分，促进根据环境问题进行适应，并防止持续存在功能失调的行为模式。可卡因依赖人群在执行控制方面表现出缺陷，这可能会降低自上而下的控制机制指导适当目标方向的有效性，从而导致他们难以保持戒断。错误监测的电生理指标已定位于前扣带回内，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，这可能是由于多巴胺转运蛋白可用性增加和/或 D2 受体结合减少所致。那么，长期使用可卡因可能会干扰多巴胺介导的监测性能，从而减弱错误处理。当一个人看到另一个人犯了错误时，就会出现一种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，并且可能受到观点采择能力和同理心关注程度等特征的影响。低共情关注可能解释了吸毒人群中外化障碍的高合并症。 Mind Research Network 最近购买了一台最先进的移动 MRI 扫描仪，在部署的头两年中，该扫描仪已用于收集 700 多名囚犯的大脑成像数据。临床数据表明，超过 65% 的囚犯患有严重的药物滥用问题。因此，这种移动 MRI 系统的部署为具有共病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“继续/不继续”反应期间-旨在引发错误的抑制任务。错误监测的电生理指标将根据大脑电位数据计算，而前扣带回的血流动力学活动将根据功能磁共振成像数据计算。还将从可卡因依赖者和匹配的健康参与者中收集唾液样本，用于研究多巴胺转运蛋白（SLC6A3）和受体（DRD2 和 DRD4）基因型。 6、12、18 和 24 个月的随访预约将用于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成为对严重可卡因滥用者样本中认知和情感异常的最大、最全面的调查，也是对这些认知/情感异常与多巴胺能多态性之间关系的首次重大调查。因此，该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，并将成为未来临床治疗方案开发的门户。心灵研究网络的最终使命是为严重的心理和精神障碍开发新颖的治疗方案，我们的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。