Functional neuromaging of cue-induced heroin craving

描述（由申请人提供）： 这是一个指导病人为导向的研究职业发展奖（K23）题为“功能性神经成像线索诱导海洛因渴望”的应用程序。候选人以前的培训和经验是在临床精神病学和核医学。通过这个提议，候选人寻求获得以下方面的高级培训：（1）功能磁共振成像（fMRI）和与成瘾研究相关的认知神经科学方法;（2）临床研究设计和分析，特别强调fMRI数据的高级统计分析和功效分析。本研究将利用功能磁共振成像和实验心理学方法，研究海洛因相关线索诱导的药物渴求过程中局部脑血流量（CBF）的变化，以确定介导阿片类药物渴求的脑网络。 研究人员在候选人的实验室和机构的研究奠定了阿片类药物依赖患者和动脉自旋标记（灌注）功能磁共振成像的药物相关的条件反射的原则。灌注功能磁共振成像特别适合于成像相对较长的状态（例如线索诱导的渴望）和涉及重复的受试者内实验的协议，这些实验间隔数天或数周，例如研究慢性药物效应。候选人在阿片类药物依赖的管理方面具有丰富的经验。候选人正在进行的试点研究表明，在美沙酮维持患者中，腹侧被盖区的激活与阿片类药物相关线索诱导的海洛因渴望之间存在关联。拟议的项目将扩大和阐述以前的调查结果和技术发展。 具体目标1是使用功能性磁共振成像的特点的提示引起的海洛因渴求的CBF响应的模式，并确定这种模式的特异性阿片类药物依赖的科目，建立在试点数据的候选人。具体目标2是确定美沙酮维持患者对阿片类药物相关线索的CBF反应是否受到美沙酮血浆水平波动的调节。具体目标3是描述阿片拮抗剂纳洛酮对戒断的阿片依赖患者对阿片相关线索的CBF反应的影响。 这项研究计划将有助于确定特定的大脑结构的作用，这些结构介导了对阿片类药物的线索诱导的渴望，并可能影响到其他药物滥用对中皮质边缘奖励系统的作用。这些数据将提高我们对依赖性、耐药性和复发的潜在机制的理解。此外，它可能为开发新的方法来评估药物治疗的疗效和药物依赖的个体治疗反应预测指明了方向。这个培训和研究计划的实施将帮助候选人成为成瘾神经精神病学的独立调查员。

DESCRIPTION (provided by applicant): This is an application for a Mentored Patient-Oriented Research Career Development Award (K23) entitled "Functional neuroimaging of cue-induced heroin craving". The candidate's previous training and experience was in clinical psychiatry and nuclear medicine. Through this proposal, the candidate seeks to gain advanced training in: (1) functional magnetic resonance imaging (fMRI) and cognitive neuroscience methodology relevant to addiction research; (2) clinical research design and analysis, with a special emphasis on advanced statistical analysis of fMRI data and power analyses. The research project that is designed to complement this training program will use fMRI and experimental psychology methods to investigate the regional cerebral blood flow (CBF) changes during drug craving induced by heroin-related cues to identify the brain networks mediating opiate craving. Studies by the investigators at candidates' laboratory and institution laid out the principles of drug-related conditioned response in opiate-dependent patients and of Arterial Spin Labeling (perfusion) fMRI. Perfusion fMRI is particularly well suited for imaging of relatively prolonged states (e.g. cue-induced craving) and protocols involving repeated within-subject experiments separated by days or weeks, such as the study of chronic medication effects. The candidate has extensive experience in the management of opiate dependence. An on-going pilot study by the candidate suggests an association between activation of the ventral tegmental area and heroin craving induced by opiate-related cues in methadone-maintained patients. The proposed project will expand and elaborate upon the previous findings and technological developments. Specific Aim 1 is to use fMRI to characterize the pattern of CBF response to cue-induced heroin craving and determine the specificity of this pattern in opiate-dependent subjects, building on the pilot data obtained by the candidate. Specific Aim 2 is to determine whether the CBF response to opiate-related cues in methadone-maintained patients is modulated by the fluctuation in methadone plasma levels. Specific Aim 3 is to characterize the effect of the opiate antagonist naltrexone on the CBF response to opiate-related cues in abstinent formerly opiate-dependent patients. The research plan will help determine the role of specific brain structures that mediate cue-induced craving to opiates and potentially to other drugs abuse acting on the mesocorticolimbic reward system. This data would improve our understanding of the mechanisms underlying dependence, treatment resistance and relapse. Furthermore, it may point the way for the development of novel methods for evaluation of the efficacy of pharmacotherapies and individual treatment response prediction in drug dependence. Implementation of this training and research plan will help the candidate to become an independent investigator in the neuropsychiatry of addiction.