A Novel Neuromonitoring Guided Cognitive Intervention for Targeted Enhancement of Working Memory

项目摘要 本申请是对NOT-MH-21-120的直接回应，专门用于COVID-1的行政补充。 19影响NIMH研究。本行政补充申请的目的是请求补充 完成母多期临床试验研究第一阶段（R61）中提出的目标的资金 (R61/R33阶段奖），以检查一种新的神经监测引导的认知干预对 有针对性地增强工作记忆。R61试验阶段已暂停8个月，原因是 2019冠状病毒病疫情，并于二零二零年十一月恢复。补充资金对于确保 R61阶段提出的目标将在无费用延长期内实现。父母多- 阶段奖励的设计是为了使奖励向R33阶段的过渡取决于满足 R61阶段的通过/不通过里程碑。因此，如果不完成R61阶段的目标， 进入下一阶段的奖励，旨在检查拟议干预措施的临床疗效。每 NOT-MH-21-120指示，本补充是在父母补助金的范围内。我们已经用尽了各种 替代性非货币解决方案，以挽救我们的协议免受COVID-19相关中断。 父母补助金中提出的干预措施包括将计算机化的WM培训与真实的- 时间fNIRS神经监测和神经反馈，通过强化策略指导干预 最大化目标WM网络的参与。在R61/R33补助金的R61阶段，我们 建议评估目标接合、有效剂量和可行性。60例ADHD儿童伴WM 将缺陷患者随机分配至治疗组（N = 30）或对照组（N = 30）。两组都将使用 一系列神经影像临床和行为评估特别是，我们将测试干预是否会导致 在额顶叶网络中的正常活动（减少活动减退）和改善WM性能 在N-back任务期间。如果干预导致目标参与和WM绩效的改善 根据建议的标准，我们将推进到R33阶段，以测试建议的临床疗效。 干预，而不是积极的比较干预，在更大的样本。 该补充将支付16名患者的入组和完成数据收集/分析的费用 在无成本延长期内，以满足目标并完成R61阶段提出的目标。 所提出的方法的验证将为开发个性化的，以病理学为重点的， 交叉诊断干预措施，可以显着提高病人的结果和公共卫生。

PROJECT SUMMARY This application is in direct response to NOT-MH-21-120 dedicated to administrative supplements for COVID- 19 impacted NIMH research. The goal of this administrative supplement application is to request supplemental funding to complete the goals proposed in the first phase (R61) of the parent multi-phase clinical trial study (R61/R33 phased award) to examine the effect of a novel neuromonitoring guided cognitive intervention for targeted enhancement of working memory. The R61 phase of the trial has been on hold for 8 months due to COVID-19 pandemic and resumed in November 2020. The supplemental funding is critical to ensure that the goals proposed in the R61 phase will be accomplished during the no-cost-extension period. The parent multi- phase award is designed so that the transition to the R33 phase of the award is contingent upon meeting go/no-go milestones in the R61 phase. Thus, without completing the goals of the R61 phase, we cannot move on to next phase of the award that is designed to examine the clinical efficacy of the proposed intervention. Per NOT-MH-21-120 instructions, this supplement is within scope of the parent grant. We have exhausted various alternative non-monetary solutions to rescue our protocol from the COVID-19 related disruption. The intervention proposed in the parent grant involves integrating computerized WM training with real- time fNIRS neuromonitoring and neurofeedback to guide the intervention through reinforcement of a strategy that maximizes the engagement of the target WM network. In the R61 phase of the parent R61/R33 grant, we proposed to assess target engagement, effective dose and feasibility. Sixty children with ADHD with WM deficits will be randomized to treatment (N = 30) or control (N = 30) groups. Both groups will be assessed using a set of neuroimaging, clinical and behavioral assessments. Particularly, we will test if the intervention results in normalized activity (reduced hypoactivity) in the frontal-parietal network and improved WM performance during N-back task. If the intervention results in improvement in target engagement and WM performance based on the proposed criteria, we will advance to the R33 phase to test the clinical efficacy of the proposed intervention, versus an active comparison intervention, in a larger sample. The supplement will cover the cost of enrolling and completing data collection/analysis for 16 patients during the no-cost extension period to meet the targets and accomplish the goals proposed in the R61 phase. Validation of the proposed approach will provide a foundation for developing personalized, pathology- focused, cross-diagnostic interventions and could significantly enhance patient outcomes and public health.