Foundational Elements of an Alternate Scientific Approach to Developing Veteran-centric Precision Cognitive Restoration Interventions

这个尖顶的目的是确定资深定制的ITBS的可扩展性的支持和障碍，以及 适用于神经学条件，较长期的目标是为 更广泛的认知康复策略，以优化每个退伍军人在日常生活中的认知功能。之后 退伍军人接受标准认知康复，认知障碍往往持续存在，如果他们真的有所收获 对日常功能的结转有限。精确神经康复的原则表明， 干预将优化收益和结转，但认知康复的精确定制只会是 如果研究人员开发和测试可扩展的方法来识别、组织和分析 许多退伍军人特有的变量驱动和影响治疗反应。与这种需求相一致， 该项目解决了长期存在的理解治疗反应的科学障碍，特别是 研究样本的异质性和个体变异性。我们通过链接来解决研究样本的异质性 退伍军人，根据认知损害程度，包括脑外伤和缺血性中风。我们创建了一个队列 具有相同认知障碍水平的退伍军人，从而能够解释以人为中心 影响治疗反应性和对日常功能影响的因素。为了进一步扩大科学的规模 精确的神经康复，我们推进了对如何设计跨学科的 而不是学习。我们将通过利用我们的 间歇性Theta Burst刺激(ITBS)和ITBS知识与注意加工训练相结合 练习(ITBS APT)。ITBS是有利的，因为它只需一次治疗就能有力地改善工作记忆 会议。这些干预措施加在一起是有利的，因为它们都可以根据退伍军人的独特情况量身定做 认知挑战，并针对每个退伍军人的神经病理独特的神经部位。这两个 干预措施还直接解决认知缺陷，同时诱导神经可塑性。 被神经损伤所阻碍或损害的区域。在这个尖顶项目中，我们将适度地研究退伍军人 认知受损，在标准认知康复后，继续与日常生活需要作斗争 协助进行复杂的日常生活工具活动(IADL)。退伍军人将参加一系列的两个 受试者内治疗研究，在两天内进行，相隔2周。退伍军人将随机 分配给他们首先接收活动ITBS或安慰剂ITBS的单个会话，然后他们将收到APT配对 与他们分配的ITBS(主动ITBS APT与安慰剂ITBS APT)进行比较。我们将测试诊断是否缓和了 这些干预措施对认知方面的即时和持久变化都有影响。为了立竿见影， 我们使用一种新的测试电池，为了获得持久的收益，我们使用已建立的和可行的神经心理测试 以及在IADL期间建立的认知功能测试。尖顶的结果将被用来获得飞行员 数据并检查与退伍军人疲劳、情绪和退伍军人报告相关的学习损耗的可行性 研究设计关键方面的适宜性。这些发现将被用来发展未来的学科内优点 交叉研究检验了将ITBS和APT量身定做的总体假设应用于跨诊断 根据生物型算法，样本并随后与退伍军人匹配将产生更好的功能 老将看重的IADL表现。提高科学能力培养精密老兵量身定制 优化日常生活认知功能的跨诊断神经康复干预与VA保持一致 RR&D的使命是创造知识和创新，促进我们的康复保健和护理 退伍军人。

The purpose of this SPiRE is to identify the supports and barriers to scalability of Veteran-tailored iTBS and APT across neurologic conditions, with the longer-term goal of providing an empirical basis for the tailoring of a broader range of cognitive rehabilitation strategies to optimize each Veteran’s cognitve function in daily life. After Veterans receive standard cognitve rehabilitation, cognitive impairments often persist and if they do make gains there is limited carry-over to daily function. The tenets of precision neurorehabilitation suggest that tailored interventions will optimize gains and carry-over, but precision-tailoring of cognitive rehabilitation will only be possible if researchers develop and test scalable approaches for identifying, organizing, and analyzing the multitude of Veteran-specific variables driving and influencing treatment responsiveness. Aligned with this need, this project addresses long-standing scientific barriers to understanding treatment responsiveness, particularly study sample heterogeneity and individual variability. We address study sample heterogeneity by linking Veterans, across TBI and ischemic stroke, according to levels of cognitve impairment. We create a cohort of Veterans with a homogeneous level of cognitve impairment, thereby enabling explication of person-centric factors influencing treatment responsiveness and carry-over to daily function. To further scale-up the science of precision neurorehabilitation, we advance understanding of how to design within-subject cross- over studies. Advancing understanding of the basic study design elements will be achieved by leveraging our knowledge of intermittent Theta Burst Stimulation (iTBS) and iTBS paired with Attention Processing Training exercises (iTBS + APT). iTBS is advantageous as it robustly improves working memory with just one treatment session. These interventions, together, are advantageous as they can each be tailored to a Veteran’s unique cognitve challenges and to target the neural site, unique to each Veteran’s neuropathology. These two interventions also directly address cognitive deficits, while simultaneously inducing neuroplasticity in neural regions hampered or impaired by neural injury. For this SPiRE project, we will study Veterans with moderately impaired cognition who, after standard cognitve rehabilitation, continue to struggle with daily life requiring assistance with complex instrumental activities of daily living (IADL). Veterans will participate in a series of two within-subject treatment studies, conducted on two separate days, 2-weeks apart. Veterans will be randomly assigned to first receive a single session of Active iTBS or Placebo iTBS and then they will receive APT paired with their assigned iTBS (Active iTBS + APT vs Placebo iTBS + APT). We will test if diagnosis moderates the effects of these interventions on both immediate and persisting change in cognition. For immediate effects, we use a novel testing battery and for persisting gains we use established and feasible neuropsychological tests as well as an established test of cognitive function during IADL. The SPiRE results will be used to obtain pilot data and examine feasibility in terms of study attrition relative to Veteran fatigue, mood and Veteran reports of suitability of key aspects of the study design. These findings will be used to develop a future merit within-subject cross-over study examining the over-arching hypothesis that tailored iTBS and APT applied to a transdiagnostic sample and subsequently matched to a Veteran, according to a biotype algorithm, will result in better functional performance of Veteran-valued IADL. Advancing scientific capability to develop precision Veteran-tailored transdiagnostic neurorehabilitation interventions that optimize cognitve function in daily life is aligned with VA RR&D's mission to create knowledge and innovations advancing the rehabilitative health and care of our Veterans.