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

项目总结 此应用程序直接响应NOT-MH-21-120专门用于COVID的行政补充- 19影响了NIMH的研究。此行政补充申请的目标是请求补充 为完成母公司多阶段临床试验研究第一阶段(R61)提出的目标而提供的资金 (R61/R33分阶段奖)，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。由于以下原因，R61阶段的试验已暂停8个月 新冠肺炎大流行，并于2020年11月恢复。补充资金对于确保 在R61阶段提出的目标将在无费用延期期间实现。父代多- 阶段奖励的设计使过渡到R33阶段的奖励取决于会议 R61阶段中的进行/不进行里程碑。因此，如果不完成R61阶段的目标，我们就不能前进。 进入该奖项的下一阶段，旨在检查拟议干预的临床疗效。人均 Not-MH-21-120说明书，本补充内容在家长资助范围内。我们已经用尽了各种 替代非货币解决方案，将我们的协议从与新冠肺炎相关的中断中拯救出来。 家长资助中建议的干预措施包括将计算机化的WM培训与真实的- 近红外神经监测和神经反馈通过加强策略来指导干预的时间 从而最大限度地提高目标WM网络的参与度。在父R61/R33赠款的R61阶段，我们 建议评估目标参与度、有效剂量和可行性。60例患有多动症的西医儿童 缺陷将被随机分为治疗组(N=30)和对照组(N=30)。两组都将使用以下工具进行评估 一套神经成像、临床和行为评估。特别是，我们将测试干预的结果是否 额顶神经网络的正常化活动(减少活动不足)和改善的WM表现 在N-Back任务中。如果干预导致目标参与度和工作管理绩效的改善 根据建议的准则，我们将进入R33阶段，以测试建议的临床疗效 在更大的样本中进行干预，而不是积极的比较干预。 这项补充费用将涵盖登记和完成16名患者的数据收集/分析的费用 在无成本延长期内完成R61阶段提出的目标和目标。 对所提出的方法的验证将为开发个性化的、以病理为重点的 交叉诊断干预措施，并可显著改善患者预后和公共健康。

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.