Neural mechanisms of galantamine treatment for cocaine dependence

加兰他敏治疗可卡因依赖的神经机制

基本信息

批准号：
9033390
负责人：
Sarah Yip
金额：
$ 18.07万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-01 至 2021-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9033390
关键词：
Abstinence Acetylcysteine Affective Aftercare Amygdaloid structure Anterior Antidepressive Agents Area Behavior Therapy Biological Neural Networks Brain Clinical Clinical Trials Cocaine Cocaine Dependence Cognitive Cognitive Therapy Combined Modality Therapy Conflict (Psychology)Corpus striatum structure Crossover Design Cysteine Data Data Analyses Data Collection Development Double-Blind Method Effectiveness Emotional Emotions Ethics Functional Magnetic Resonance Imaging Galantamine Genetic Crossing Over Glutamates Goals Homeostasis Human Individual Individual Differences Inferior frontal gyrus Insula of Reil Intervention Intervention Studies Magnetic Resonance Mentored Research Scientist Development Award Mentors Methadone Methods Network-based Neurobiology Neurosciences Outcome Patients Performance Pharmaceutical Preparations Pharmacology Pharmacotherapy Pilot Projects Placebo Control Placebos Population Preparation Process Public Health Randomized Randomized Clinical Trials Research Research Design Research Personnel Research Training Residual state Role Science Signal Transduction Structure Supervision System Training Training Programs Work addiction base care burden cholinergic clinical investigation clinically significant cocaine use cognitive control computerized depressive symptoms design effective intervention effective therapy emotion regulation executive function experience improved independent component analysis innovation insight medical schools neurobiological mechanism neuroimaging neuromechanism novel pre-clinical programs public health relevance putamen relating to nervous system response restoration skills sustained attention symposium theories treatment as usual treatment response

项目摘要

DESCRIPTION (provided by applicant): The program of research and training described in this Mentored Research Scientist Development Award (MRSDA) K01 application will provide the candidate with the requisite skills to become an independent investigator in the field of addictions neuroscience, studying the neural mechanisms of emerging pharmacotherapies in order to improve treatments for cocaine-dependence. In pursuit of this goal, the candidate proposes to undertake further training in three primary areas: (1) clinical intervention research science; (2) addictions pharmacology (in particular the pharmacology of emerging medications); and (3) advanced functional magnetic resonance (fMRI) analysis methods (e.g., spatial independent component analysis; sICA). The opportunities afforded by the K01 mechanism would enable the candidate to embark on a rigorous, structured 5-year program of training and research, designed to provide her with the necessary skills in the three areas highlighted above. This program of study will combine formal didactic training (e.g., courses on Ethical and Practical Issues in Clinical Investigation and on Pharmacology at the School of Medicine), one-on-one tutorials, attendance at scientific research conferences and mentored research experience. The research component of this 5-year plan involves the application of advanced fMRI analysis methods to identify the functional brain mechanisms associated with: 1) Galantamine treatment for cocaine dependence: Pre- and post-treatment fMRI data from 60 individuals who participated in a newly completed randomized clinical trial (RCT) of galantamine alone and in combination with computerized cognitive behavioral therapy (2x2 factorial design) will be analyzed using sICA. This work will focus on fMRI Stroop-task data to understand the relationship between cognitive control processes and cocaine-use outcomes following treatment with galantamine. 2) N-acetylcysteine (NAC) administration in cocaine dependence: FMRI data will be collected before and after 7-day NAC administration using a randomized, placebo-controlled, cross-over design (n=40) and will be analyzed using sICA. This work will focus on the neural networks engaged during response-inhibition and during emotion-regulation, in order to provide mechanistic insight into findings from recently completed and ongoing clinical trials of NAC treatment for cocaine-dependence. This combination of secondary data analyses and novel data collection is designed to maximize the candidate's training via provision of hands-on experience in both: (1) the analysis and interpretation of neuroimaging data from a large-scale pharmacotherapy trial (CBT4CBT & Galantamine; P50DA009241) and; (2) the theory and conduct of her own combined fMRI-medication study under guided supervision of recognized experts.

描述（由应用程序提供）：该指导研究科学家发展奖（MRSDA）中描述的研究和培训计划K01应用程序将为候选人提供所需的技能，以成为成瘾领域的独立研究者，研究新兴药物治疗的神经力学，以改善可依赖性依赖性的cocaine依赖性治疗。为了实现这一目标，候选人提案要在三个主要领域进行进一步培训：（1）临床干预研究科学；（2）成瘾药理学（特别是新兴药物的药理学）；（3）高级功能磁共振（fMRI）分析方法（例如，空间独立组件分析； SICA）。 K01机制提供的机会将使候选人能够着手进行严格的，结构化的5年培训和研究计划，旨在为她提供上面突出的三个领域的必要技能。该研究计划将结合正式的教学培训（例如，关于医学院临床研究和药理学的道德和实践问题的课程），一对一的教程，科学研究会议的出席和修改研究经验。该五年计划的研究组成部分涉及应用高级fMRI分析方法来确定与可卡因依赖性的葡萄球治疗相关的功能性大脑机制：从60个患者进行了fMRI的fMRI数据：来自60名参与新近完成的随机临床试验（RCT）的人（RCT）与计算机分析（RCT）进行了分析的行为（2）西卡。这项工作将重点放在fMRI Stroop任务数据上，以了解用甘氨酸治疗后认知控制过程与可卡因使用结果之间的关系。 2）可卡因依赖性的N-乙酰半胱氨酸（NAC）给药：FMRI数据将在7天NAC之前和之后使用随机的，安慰剂控制的，跨界设计（n = 40）收集，并将使用SICA分析。这项工作将重点放在抑制响应期间和情绪调节过程中所参与的神经元网络，以便从最近完成的NAC治疗可卡因依赖性的NAC治疗中对发现的机械见解。辅助数据分析和新型数据收集的这种组合旨在通过提供动手实践经验来最大化候选人的培训：（1）从大规模的药物疗法试验（CBT4CBT＆Galantamine; P50DA009241）和;;;；（2）在公认的专家的指导监督下，她自己的fMRI介绍研究的理论和行为。