Neurocircuitry of Prospective Memory in Veterans with Mild Traumatic Brain Injury

轻度创伤性脑损伤（mTBI）的发生率在战斗退伍军人中很高，报告表明， 10-20%的伊拉克和阿富汗退伍军人符合mTBI的诊断标准，其中绝大多数是 与爆炸有关。关于爆炸相关的mTBI是否可能导致长期的 神经心理障碍，鉴于缺乏积极的发现，尽管不断抱怨的认知 在这个群体中的困难。对这种差异的一种可能解释是， 神经心理学测试程序可能在捕捉日常功能的细微缺陷方面缺乏敏感性， 爆炸相关的mTBI。前瞻记忆（PM）是记住在某个时间点执行某个动作的能力 或者说，这是对未来的一种期待，或者说是对未来的一种期待。PM可能对功能困难更敏感 由一些患有mTBI的退伍军人描述（例如，忘记约会）比那些领域通常评估 (e.g.,执行功能、注意力和回顾性记忆）。功能性神经影像学研究结果 表明PM依赖于由前额叶皮层组成的前引导皮层网络， 背外侧前额叶皮层、前扣带皮层和顶叶皮层。白色的神经结构损伤 整合这一网络的物质途径提出了PM中断的可能潜在机制， mTBI。迄今为止，很少有研究调查了mTBI对PM的影响，也没有发表的研究 研究了具有爆炸相关mTBI病史的OEF/OIF退伍军人中PM的神经回路。拟议 研究旨在利用神经心理学评估和综合多模态神经成像分析， 研究具有爆炸相关mTBI病史的退伍军人的前瞻性记忆（PM）功能。80名参与者 将从现有VA资助的TBI研究中招募，并将包括有病史的退伍军人 爆炸相关mTBI（n = 40）或无mTBI病史的部署退伍军人（n = 40）。参与者将 完成广泛的神经认知评估，包括PM问卷和客观的测量， 下午.退伍军人还将接受MRI扫描，其中包括扩散张量成像（DTI）和完成一个 PM fMRI任务。该研究的目的是调查有爆炸相关历史的退伍军人的PM性能 mTBI，通过整合fMRI和DTI模式研究与PM功能相关的神经网络 并确定这个网络是否对患有mTBI的退伍军人造成了破坏。 该候选人目前是一名研究mTBI和神经影像学研究的VA博士后研究员， mTBI的神经心理学评估，已经证明了学习神经影像学研究的能力 方法在多种成像模式，并已与拟议的指导团队合作， 几个先前的拨款申请和手稿有关的神经成像和认知功能后TBI。 成功完成此VA职业发展奖-2与推进候选人进一步走向 长期研究职业目标是成为VA的独立临床研究人员，专注于 脑外伤研究中神经影像学和神经心理学评估的整合。CDA-2将导致 独立性不仅体现在开展拟议研究和培训计划的经验方面， 为退伍军人管理局优异奖提供关键的飞行员数据本CDA-2的具体近期培训目标 是：（1）发展整合神经成像模式，包括功能磁共振成像和DTI的专业知识，（2）发展 在前瞻性记忆研究的专业知识，（3）实现先进的生物统计学的熟练程度和（4）继续 我的职业发展目标是从一个博士后过渡到一个独立的VA 临床科学家这些目标将通过与确定的指导团队合作来实现， 提供神经心理学评估、创伤性脑损伤研究和神经影像学方面的进一步专业培训 技术.

Rates of mild traumatic brain injury (mTBI) are high among combat veterans, with reports suggesting 10-20% of Iraq and Afghanistan Veterans meet diagnostic criteria for mTBI, the vast majority of which being related to explosive blasts. There is on-going debate as to whether blast-related mTBI may result in long-term neuropsychological impairment, given the paucity of positive findings, despite on-going complaints of cognitive difficulties within this cohort. One possible explanation for this discrepancy is that traditional neuropsychological test procedures may lack sensitivity in capturing subtle deficits in everyday functioning in blast-related mTBI. Prospective memory (PM) is the ability to remember to execute an action at a certain point in the future, or is the fulfillment of delayed intentions. PM may be more sensitive to the functional difficulties described by some Veterans with mTBI (e.g., forgetting appointments) than those domains typically assessed (e.g., executive functions, attention and retrospective memory). Results of functional neuroimaging studies suggest that PM is dependent on a frontally-guided cortical network comprised of the anterior prefrontal cortex, dorsolateral prefrontal cortex, the anterior cingulate and parietal cortex. Neurostructural damage to the white matter pathways that integrate this network presents a possible underlying mechanism for PM disruption in mTBI. To date, few studies have investigated the effect of mTBI on PM, and no published studies have investigated the neurocircuitry of PM in OEF/OIF Veterans with a history of blast-related mTBI. The proposed study aims to utilize neuropsychological assessment and an integrated multi-modal neuroimaging analysis to study prospective memory (PM) functioning in Veterans with histories of blast-related mTBI. Eighty participants will be recruited from within an existing VA-funded TBI research study and will include Veterans with a history of blast-related mTBI (n = 40) or deployed Veterans without a history of mTBI (n = 40). Participants will complete a broad neurocognitive assessment which includes PM questionnaires and objective measures of PM. Veterans will also undergo an MRI scan which includes diffusion tensor imaging (DTI) and completion of a PM fMRI task. The study aims are to investigate PM performance in Veterans with histories of blast-related mTBI, investigate the neural network associated with PM functions via integration of fMRI and DTI modalities and determine whether this network is disrupted for Veterans with mTBI. The candidate is a current VA postdoctoral fellow studying mTBI and neuroimaging research, has trained in the neuropsychological assessment of mTBI, has demonstrated a capacity to learn neuroimaging research methods across multiple imaging modalities and has collaborated with the proposed mentorship team on several prior grant applications and manuscripts related to neuroimaging and cognitive functions following TBI. Successful completion of this VA Career Development Award-2 with advance the candidate further toward a long-term research career goal of being an independent clinical researcher in the VA focusing on the integration of neuroimaging and neuropsychological assessment in the study of TBI. The CDA-2 will lead to independence not only through the experience of conducting the proposed research and training plan, but also by providing critical pilot data for a VA Merit Award. The specific immediate training objectives of this CDA-2 are to: (1) develop expertise in integrating neuroimaging modalities including fMRI and DTI, (2) develop expertise in the study of prospective memory, (3) achieve proficiency in advanced biostatistics and (4) continue my professional development aimed toward transitioning from a postdoctoral fellow into an independent VA clinical scientist. These goals will be achieved via collaboration with the identified mentorship team that will provide further specialized training in neuropsychological assessment, TBI research and neuroimaging techniques.