Cortical Inhibition and Corpus Callosum Integrity in Cocaine Users

描述(申请人提供)：这是一个通过“导师研究科学家发展奖”(K01)机制申请5年资助的申请。申请者科琳·汉伦博士是一名神经生物学家，有使用功能磁共振成像检查慢性可卡因使用者所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质活动的变化，本申请提出了扩散张量成像(DTI)和经颅磁刺激(TMS)方面的培训计划。申请者的长期目标是成为一名独立的调查员，熟练应用多种成像模式，这些模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。职业发展也是这项申请的一个重要组成部分，时间用于培训负责任的研究行为、手稿和拨款撰写、指导学生、参加科学会议以及与机构审查委员会的互动。这一奖项的研究部分是由汉伦博士完成的先前由NIH资助的研究的延伸，并经过精心设计，以配合培训计划。这项建议的首要目标是确定在多大程度上，长期吸食可卡因的人皮质中非典型的大胆信号变化与胼胝体完整性(特定目标1)和皮质抑制音(特定目标2)的变化有关。除了扩大对感觉运动偏侧性的研究外，还将讨论皮层偏侧性丧失对可卡因使用者认知功能的影响(具体目标#3)。这些实验将揭示在多大程度上，皮质抑制音和穹隆体完整性的变化可能会导致慢性可卡因使用者的神经功能和行为缺陷。这些实验的结果将被用于进一步研究和开发兴奋剂依赖患者的治疗策略。 公共卫生相关性：这是一项通过“指导研究科学家发展奖”(K01)机制提供5年资金的申请。申请者科琳·汉伦博士是一名神经生物学家，有使用功能磁共振成像检查慢性可卡因使用者所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质活动的变化，本申请提出了扩散张量成像(DTI)和经颅磁刺激(TMS)方面的培训计划。申请者的长期目标是成为一名独立的调查员，熟练应用多种成像模式，这些模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。职业发展也是这项申请的一个重要组成部分，时间用于培训负责任的研究行为、手稿和拨款撰写、指导学生、参加科学会议以及与机构审查委员会的互动。这一奖项的研究部分是由汉伦博士完成的先前由NIH资助的研究的延伸，并经过精心设计，以配合培训计划。这项建议的首要目标是确定在多大程度上，长期吸食可卡因的人皮质中非典型的大胆信号变化与胼胝体完整性(特定目标1)和皮质抑制音(特定目标2)的变化有关。除了扩大对感觉运动偏侧性的研究外，还将讨论皮层偏侧性丧失对可卡因使用者认知功能的影响(具体目标#3)。这些实验将揭示在多大程度上，皮质抑制音和穹隆体完整性的变化可能会导致慢性可卡因使用者的神经功能和行为缺陷。这些实验的结果将被用于进一步研究和开发兴奋剂依赖患者的治疗策略。

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.