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对自身监测和他人在可卡因依赖性个体中的行为为基础的神经过程的完整性，并探讨这些过程与多巴胺转运蛋白和受体多态性的功能之间的关系。监视自己的行为的能力是行政控制的核心组成部分，根据环境问题促进适应，并防止对功能失调的行动模式的坚持。可卡因依赖人群表明，执行控制中的缺陷可能是由于降低自上而下的控制机制的疗效以指导适当的目标方向而难以避免的困难。误差监测的电生理指标已定位在前扣带回中，据信依赖于适当的中唇多巴胺能流到前扣带回。慢性可卡因的使用已与前扣带回中的多巴胺能张力降低相关，这可能是由于多巴胺转运蛋白的可用性和/或D2受体结合降低所致。然后，慢性可卡因的使用可能会通过干扰多巴胺介导的监测性能来减轻错误处理。已经记录了类似的与错误相关的电生理签名，当一个人认为另一个人犯错时发生。与观察者误差相关的负性（OERN）似乎有能力充当移情问题的基本指标。监测他人行为的能力反过来可能是观察学习的基础，并且可能受到诸如观点的能力和移情关注水平之类的特征的影响。较低的移情问题可能解释了毒品滥用人群中外在性疾病的高合并症。 Mind Research网络最近获得了最先进的移动MRI扫描仪，该扫描仪已用于在部署的头两年中收集700多名囚犯的脑成像数据。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，该移动MRI系统的部署为具有合并外部化特征的严重可卡因施虐者人群提供了前所未有的访问。通过此访问，我们建议在300名被监禁的参与者中收集多模式（EEG/FMRI）数据，分为可卡因虐待和非卡通滥用组，在执行过程中，并观察到旨在引起错误的GO/No-do响应抑制任务。错误监测的电生理指标将从大脑电位数据中计算出来，而前扣带回的血液动力学活性将从fMRI数据中计算出来。唾液样本还将从可卡因依赖性和匹配的健康参与者中收集，以研究多巴胺转运蛋白（SLC6A3）和受体（DRD2和DRD4）基因型。六，12-18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。通过该项目获得的数据将是严重可卡因滥用者样本中认知和情感异常的最大，最全面的研究，以及对这些认知/情感异常和多巴胺能多态性之间关系的首次重大研究。因此，这项研究将提供有关可卡因依赖性神经认知和遗传基础的重要信息，并将作为开发未来临床治疗方案的门户。思维研究网络的最终任务是开发针对严重的心理和精神障碍的新型治疗计划，而我们的小组则将从这项研究收集的数据设想为迈向未来工作的重要一步。