Sustained Attention and Executive Functioning After Brain Trauma

脑外伤后的持续注意力和执行功能

• 批准号: 9301682
• 负责人: Corina Oana Bondi
• 金额: $ 7.7万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9301682
• 关键词: Address; Affect; Animal Model; Anterior; Applications Grants; Attention; Behavior; Behavioral; Brain; Brain Injuries; Brain region; Cell Death; Cessation of life; Clinic; Cognition; Cognitive; Complex; Corpus striatum structure; Data; Dimensions; Dopamine; Dorsal; Estrus; Feedback; Female; Future; Goals; Grant; Health Care Costs; Hippocampus (Brain); Impaired cognition; Impairment; Individual; Injury; Ipsilateral; Laboratories; Learning; Lesion; Measures; Medial; Mediating; Memory; Memory Loss; Mild Concussions; Modeling; Motor; Nervous System Trauma; Performance; Pharmacology; Play; Population; Prefrontal Cortex; Presynaptic Terminals; Productivity; Proteins; Rattus; Reaction Time; Regulation; Rehabilitation Research; Rehabilitation therapy; Role; Societies; Stimulus; Survivors; Testing; Translations; Trauma; Traumatic Brain Injury; Tryptophan 5-monooxygenase; Tyrosine 3-Monooxygenase; United States; United States National Institutes of Health; Work; behavior test; bench to bedside; cingulate cortex; clinically relevant; cognitive function; cognitive performance; cognitive process; controlled cortical impact; design; disability; distraction; executive function; flexibility; frontal lobe; male; monoamine; neurotransmission; premature; psychologic; response; sustained attention; therapeutic target; vesicular monoamine transporter 2

ABSTRACT Traumatic brain injury (TBI) affects 2 million individuals in the United States each year, ranging from mild concussions to severe trauma or, in about 50,000 cases, even death. TBI survivors endure long-lasting memory loss and cognitive impairments associated with frontal lobe disturbances, as well as psychological consequences. TBI models in the laboratory have been associated for decades with declines in long-term learning and memory, although the types of behavioral tests performed to date have not focused on the complex attention impairments related to the frontal lobe, which are common in most brain injuries. Specifically, higher-order cognitive capabilities such as sustained attention and executive functioning are significantly affected by TBI and represent sophisticated brain capacities to direct and focus cognitive activity on specific stimuli or use environmental feedback to “unlearn” a previously valid set of rules, switch gears and filter unwanted distractions, respectively. The overarching aim of this proposal is to assess clinically- relevant cognitive-behavioral dimensions sensitive to TBI, and to begin to address mechanistic questions regarding altered neurotransmission responsible for such behavioral deficits. Specifically, the aims are designed to 1) determine higher-order cognitive function capabilities, namely sustained attention via the 3-choice serial reaction time task and cognitive flexibility via the attentional set-shifting test, after moderate TBI, which are tasks that have not been assessed after experimental TBI and 2) evaluate moderate TBI-induced changes in brain markers of monoamine regulation, such as vesicular monoamine transporter 2, tryptophan hydroxylase and tyrosine hydroxylase in [discrete brain regions critical for directly or indirectly modulating] goal directed behavior and executive function. The proposed studies will be carried out in both male and normal cycling female rats, an approach that is clinically relevant. Specifically, females account for up to 45% of the TBI population and these injuries occur independent of estrous stage and therefore evaluating normal cycling females parallels the real world. Integrating animal models of higher-order cognition in the standard neurotrauma battery of behavior after TBI as well as assessing monoamine regulation in cortical regions not well studied after TBI is paramount to investigating complex cognitive problems and finding therapeutic targets more relevant to the clinic. This two-year R03 grant will generate preliminary data that will serve as proof-of-concept for an NIH R01 individual grant application, allowing future work to also evaluate potential pharmacological and rehabilitative therapies for TBI-induced cognitive dysfunction.

抽象的 每年在美国，创伤性脑损伤（TBI）每年影响200万人 对严重创伤或大约50,000例死亡的脑震荡。 TBI存活持续了长期 与额叶障碍相关的记忆力丧失和认知障碍以及心理 结果。实验室中的TBI模型已有数十年的历史与长期下降有关 学习和记忆，尽管迄今为止执行的行为测试的类型并未集中在 与额叶有关的复杂注意力障碍，在大多数脑损伤中很常见。 具体而言，高阶认知能力（例如持续关注和执行功能）是 受TBI的显着影响，并代表了指导和集中认知活动的复杂大脑能力 在特定的刺激上或使用环境反馈“取消”以前有效的规则，开关齿轮和 分别过滤不必要的干扰。该提案的总体目的是评估临床 - 相关的认知行为维度对TBI敏感，并开始解决机理 有关对这种行为定义负责的神经传递改变的问题。具体来说， 目的设计为1）确定高阶认知功能能力，即持续关注 通过3个选择的串行反应时间任务和认知灵活性，通过注意力设定转换测试 中度TBI，这是实验性TBI后未评估的任务，2）评估中等 TBI诱导的单胺调节大脑标记变化，例如囊泡单胺转运蛋白2， 色氨酸羟化酶和酪氨酸羟化酶在[离散的大脑区域至关重要的直接或间接 调节]目标定向行为和执行功能。拟议的研究将在两者中进行 男性和正常骑自行车的雌性大鼠，一种在临床上相关的方法。特别是，女性说明 多达45％的TBI人口，这些伤害无关，因此 评估正常骑自行车的女性与现实世界平行。整合高阶动物模型 TBI之后的标准神经释放行为电池的认知以及评估单胺调节 在皮质区域中，在TBI之后未经很好的研究对于研究复杂的认知问题和 寻找与诊所更相关的治疗靶标。这项为期两年的R03赠款将生成初步数据 这将作为NIH R01个人赠款申请的概念验证，从而使未来的工作也能够 评估针对TBI诱导的认知功能障碍的潜在药物和康复疗法。