FMRI STUDIES OF BRAIN REWARD AND EMOTION

申请者摘要：这是一份招聘NIDA科学家的申请 发展奖(K21)，题为《脑奖励和脑功能磁共振研究》 情感“，这是为了回应NIDA的通知而提交的 1995财政年度研究科学家发展奖。 应聘者的主要兴趣是研究大脑机制 调解人类的动机和情感，特别是在关系中 与药物滥用和可卡因依赖的发展 或者鸦片类药物。通过专注于药物诱导的奖赏的神经生物学， 以及随后的情感记忆，这可能会鼓励 反复吸毒，建议的研究应该有重要的意义 对药物滥用临床治疗的启示。物质滥用 研究巩固了候选人的兴趣和培训 精神病学、临床药理学和功能磁学 磁共振成像(FMRI)对临床相关问题的研究。穿过 这一建议，候选人寻求在(1)人方面获得培训 可卡因和鸦片滥用的神经生物学，(2)脑的神经科学 奖励与情感，(3)实验心理学的实施 和认知神经科学范式，以及(4)功能磁共振成像的高级使用 探讨有关药物欣快感/焦虑症和 对那种欣喜/烦躁的记忆。为了进一步提高候选人的 了解功能性核磁共振，他还要求接受置换方面的培训 基于统计方法的数据分析。 为补充这一培训计划而设计的研究项目 涉及药物注射和心理学范式的使用 FMRI来研究组成腹侧被盖区的电路如何 人用药过程中的伏隔核(VTA)、伏隔核(NA)和杏仁核功能 诱导的欣快感，以及对那种欣快感的记忆。之间的电路 VTA、NA和杏仁核代表系统的十字路口。 在动物模型中研究的大脑奖励和情绪记忆。 该项目试图在人体内研究两者之间的相互作用。 可能导致重复使用物质的系统。具体而言：(A) 可卡因和吗啡对VTA、NA和杏仁核功能的影响 将与药物动力学、心血管疾病进行比较和关联 依赖和非依赖两种药物滥用者的效果和欣快感 实质性的。(B)正常对照以及依赖和非依赖 将对每种药物的滥用者进行功能磁共振成像和心理学研究 特定于奖励和情绪记忆功能的范例。这些 实验将试图回答药物依赖状态是如何 改变正常的VTA、NA和杏仁核功能。(C)最后，操作性 以可卡因和吗啡为奖赏的条件反射范式 与物质滥用者将解决是否情绪的回路 记忆在药物诱导情绪中的作用与在药物诱导时不同 由认知范式引起的情绪。这项研究将是 与培训相结合，促进应聘者发展 作为一名富有成效的独立调查员，致力于 人类动机和情绪的大脑机制及其机制 对上瘾的贡献。

APPLICANT'S ABSTRACT: This is a request for an NIDA Scientist Development Award (K21) entitled "FMRI Studies of Brain Reward and Emotion", and is submitted in response to a NIDA notice of "special research scientist development awards for fiscal year 1995." The Candidate's primary interest is in the study of brain mechanisms mediating human motivation and emotion, particularly in relation to the development of substance abuse and dependence with cocaine or opiates. By focusing on the neurobiology of drug-induced reward, and on the subsequent emotional memory which might encourage repeated drug use, the proposed research should have important implications for clinical treatment of drug abuse. Substance abuse research consolidates the Candidate's interests and training in psychiatry, clinical pharmacology, and functional magnetic resonance imaging (fMRI) on clinically relevant questions. Through this proposal, the Candidate seeks to gain training in (1) the human neurobiology of cocaine and opiate abuse, (2) the neuroscience of brain reward and emotion, (3) the implementation of experimental psychology and cognitive neuroscience paradigms, and (4) the advanced use of fMRI to probe fundamental questions regarding drug euphoria/dysphoria and memory of that euphoria/dysphoria. To further the Candidate's understanding of fMRI, he is also requesting training in permutation based statistical methods of data analysis. The research project designed to complement this training program involves the use of drug infusions and psychological paradigms with fMRI to study how a circuit comprising the ventral tegmental area (VTA), nucleus accumbens (NA) and amygdala function during human drug induced euphoria, and memory of that euphoria. The circuitry between the VTA, NA and amygdala represent the crossroads of the systems for brain reward and emotional memory as studied in animal models. This project seeks to study in humans the interaction between these systems which may drive repeated substance use. Specifically: (A) The effects of cocaine and morphine on VTA, NA and amygdala function will be compared and correlated with drug kinetics, cardiovascular effects and euphoria in dependent and nondependent abusers of each substance. (B) Normal controls along with dependent and nondependent abusers of each drug will be studied with fMRI and psychological paradigms specific to reward and emotional memory function. These experiments will seek to answer how the state of drug dependency alters normal VTA, NA and amygdala function. (C) Lastly, operant conditioning paradigms using cocaine and morphine as the rewards with substance abusers will address whether the circuitry of emotional memory works differently during drug induction of emotion than during emotions aroused by cognitive paradigms. This research will be integrated with the training to foster the Candidate's development as a productive independent investigator committed to the study of brain mechanisms underlying human motivation and emotion and their contribution to addiction.