Early Onset Cigarette smoking effects on brain structure, function and chemistry

描述(申请人提供)：这是一份通过K01“导师研究科学家发展奖”机制提供5年支持的申请。这位候选人是一名行为神经学家，有使用临床前可卡因成瘾啮齿动物模型的经验，他在麦克莱恩医院提出了一个临床研究培训计划，该计划结合了在尼古丁依赖人群中几种神经成像方法以及神经心理学和自我报告评估方面的丰富学习经验。该计划包括一对一专家指导、磁共振技术课程、数据处理和分析策略、出席药物依赖和脑成像科学会议并发表演讲、参加精神病学和神经科学研讨会，以及持续的负责任的研究行为培训。通过这些培训机会获得的技能将通过应用程序的研究部分得到实施和磨练。由于成年吸烟者表现出许多结构、功能/认知和神经化学变化，这些变化可能是早期吸烟直接导致的，这将是研究计划的重点。具体地说，拟议的研究将实现一个短期的职业目标，即整合多模式神经成像和神经心理学和自我报告评估，以开发早期(&lt；16岁)的生物学和认知概况。老年)与晚发性(？16岁。老年人)依赖尼古丁的成年人。为此，将通过三个独立的研究目标来调查早起和晚起吸烟对成年吸烟者神经生物学和认知表现的影响。首先，申请者将应用脑电/事件相关电位技术、生理活动和自我报告的渴望评级来衡量戒烟条件下吸烟线索反应性和渴望的增加。其次，申请者将学习磷磁共振波谱[31P MRS]方法，并对多个认知域(即注意力、工作记忆、冲动)进行神经心理学评估，以评估在急性尼古丁服用和戒断条件下测量的生物能量和磷脂神经代谢物水平和认知处理的变化。第三，申请者将学习如何应用扩散张量成像(DTI)方法来测量不同组之间变化的白质结构。总而言之，早发吸烟导致成人神经改变和认知缺陷的经验证据可以用来预测某些治疗方法是否应该区别对待太晚和早发吸烟者来改善戒烟结果。总体而言，拟议的培训和研究项目将在多种神经成像技术的理论和实施以及最佳研究设计、研究管理以及数据分析和解释方面提供详细的知识和培训。因此，候选人将获得必要的研究技能和工具，以过渡到长期的职业目标，通过整合多模式脑成像和神经心理学技术，作为一名创新和多才多艺的独立研究人员，为了解成瘾的神经生物学病因和认知后遗症做出有意义的贡献。

DESCRIPTION (provided by applicant): This is a request for 5 years of support through the K01 "Mentored Research Scientist Development Award" mechanism. The Candidate, a behavioral neuroscientist with experience using a preclinical rodent model of cocaine addiction, proposes a clinical research training program at McLean Hospital that combines extensive learning experience in several neuroimaging methods and in neuropsychological and self-report assessments, in a nicotine-dependent population. The program includes 1-on-1 expert mentorship, coursework in MR technology, data processing and analysis strategies, attendance and presentations at drug dependence and brain imaging scientific conferences, participation in psychiatric and neuroscience seminars, and ongoing Responsible Conduct of Research training. Skills acquired through these training opportunities will be implemented and honed through the application's research component. As adult smokers exhibit a number of structural, functional/cognitive and neurochemical changes that may result directly from early smoking, this will be the focus of the research plan. Specifically, the proposed studies will fulfill a short-ter career goal of integrating multimodal neuroimaging and neuropsychological and self-report assessments to develop a biological and cognitive profile of early- (<16 yrs. old) vs. late-onset (? 16 yrs. old) nicotine-dependent adults. To this end, the effects of early- vs. late-onset smoking on the neurobiology and cognitive performance of adult smokers will be investigated by 3 independent research aims. First, the applicant will apply EEG/ERP technology, physiological activity, and self-reported ratings of craving to measure increased smoking cue reactivity and craving during withdrawal conditions. Second, the applicant will learn phosphorus magnetic resonance spectroscopy [31P MRS] methods and to conduct neuropsychological assessments of multiple cognitive domains (i.e. attention, working memory, impulsivity) to assess alterations in bioenergetic and phospholipid neurometabolite levels and cognitive processing measured during acute nicotine administration and withdrawal conditions. Third, the applicant will learn how to apply diffusion tensor imaging (DTI) methods to measure altered white matter structure between groups. Collectively, the empirical evidence of adult neural alterations and cognitive deficits resulting from early-onset smoking may be used to predict if certain treatment approaches should be applied differentially too late- vs. early-onset smokers to improve smoking cessation outcomes. Overall, the proposed training and research projects will confer detailed knowledge and training in the theory and implementation of multiple neuroimaging techniques as well as in optimal study design, study management, and data analysis and interpretation. The Candidate will therefore acquire the research skills and tools necessary to transition into a long-term career goal of making meaningful contributions towards understanding the neurobiological etiology and cognitive sequel of addiction by integrating multimodal brain imaging and neuropsychological techniques as an innovative and versatile independent investigator.