Cortical Inhibition and Corpus Callosum Integrity in Cocaine Users

描述（由申请人提供）：这是一份通过“指导研究科学家发展奖”（K01）机制获得5年资助的申请。申请人Colleen Hanlon博士是一位神经生物学家，具有使用功能性磁共振成像检查慢性可卡因使用者受影响的神经网络的经验。为了进一步表征可卡因使用者皮层活动的变化，本应用程序提出了扩散张量成像（DTI）和经颅磁刺激（TMS）训练计划。申请人的长期目标是成为一名独立的研究者，熟练运用多种成像方式，可用于指导药物滥用人群的治疗策略。培训计划包括TMS采集和分析、DTI图像分析和多元统计方面的结构化培训课程，以及由导师团队进行的持续培训。职业发展也是这个申请的一个重要组成部分，有时间用于培训负责任的研究行为，手稿和拨款写作，指导学生，参加科学会议，以及与机构审查委员会的互动。该奖项的研究部分扩展了先前由Hanlon博士完成的nih资助的研究，并经过精心设计，与培训计划并行。该提案的总体目标是确定胼胝体完整性（特异性目标#1）和皮质抑制性张力（特异性目标#2）的变化与慢性可卡因使用者皮质非典型BOLD信号变化的关系程度。除了扩展对感觉运动侧性的研究外，还将讨论皮质侧性丧失对可卡因使用者认知功能的影响（具体目标#3）。这些实验将揭示皮质抑制性张力和胼胝体完整性的变化在多大程度上可能导致慢性可卡因使用者的神经功能和行为缺陷。这些实验的结果将用于进一步研究和发展兴奋剂依赖个体的治疗策略。

DESCRIPTION (provided by applicant): This is a request for 5 years of funding through the "Mentored Research Scientist Development Award" (K01) mechanism. The applicant, Dr. Colleen Hanlon, is a neurobiologist with experience using functional magnetic resonance imaging to examine neural networks affected in chronic cocaine users. To further characterize changes in cortical activity in cocaine users, this application proposes a program of training in diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS). The long- term goal of the applicant is to become an independent investigator, skilled in the application of multiple imaging modalities that may be used to guide treatment strategies in substance abusing populations. The training plan includes structured training courses in TMS acquisition and analysis, DTI image analysis, and multivariate statistics, as well as ongoing training by a team of mentors. Career development is also a strong component of this application with time devoted to Training in the Responsible Conduct of Research, manuscript and grant writing, mentoring students, attendance at scientific meetings, and interactions with the institutional review board. The research component of this award extends prior NIH-funded research complete by Dr. Hanlon, and has been carefully designed to parallel the training plan. The overarching goal of this proposal is to determine the extent to which changes in corpus callosum integrity (Specific Aim #1) and cortical inhibitory tone (Specific Aim #2) are related to atypical BOLD signal changes in the cortex of chronic cocaine users. In addition to extending investigations on sensorimotor laterality, the impact of loss of cortical laterality on cognitive function in cocaine users will also be addressed (Specific Aim #3). These experiments will reveal the extent to which changes in cortical inhibitory tone and corpus callosal integrity may contribute to neurofunctional and behavioral deficiencies in chronic cocaine users. The results of these experiments will be used to further the investigation and development of therapeutic treatment strategies in stimulant dependent individuals. PUBLIC HEALTH RELEVANCE: This is a request for 5 years of funding through the "Mentored Research Scientist Development Award" (K01) mechanism. The applicant, Dr. Colleen Hanlon, is a neurobiologist with experience using functional magnetic resonance imaging to examine neural networks affected in chronic cocaine users. To further characterize changes in cortical activity in cocaine users, this application proposes a program of training in diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS). The long- term goal of the applicant is to become an independent investigator, skilled in the application of multiple imaging modalities that may be used to guide treatment strategies in substance abusing populations. The training plan includes structured training courses in TMS acquisition and analysis, DTI image analysis, and multivariate statistics, as well as ongoing training by a team of mentors. Career development is also a strong component of this application with time devoted to Training in the Responsible Conduct of Research, manuscript and grant writing, mentoring students, attendance at scientific meetings, and interactions with the institutional review board. The research component of this award extends prior NIH-funded research complete by Dr. Hanlon, and has been carefully designed to parallel the training plan. The overarching goal of this proposal is to determine the extent to which changes in corpus callosum integrity (Specific Aim #1) and cortical inhibitory tone (Specific Aim #2) are related to atypical BOLD signal changes in the cortex of chronic cocaine users. In addition to extending investigations on sensorimotor laterality, the impact of loss of cortical laterality on cognitive function in cocaine users will also be addressed (Specific Aim #3). These experiments will reveal the extent to which changes in cortical inhibitory tone and corpus callosal integrity may contribute to neurofunctional and behavioral deficiencies in chronic cocaine users. The results of these experiments will be used to further the investigation and development of therapeutic treatment strategies in stimulant dependent individuals.