Neuroplasticity-Based Computerized Cognitive Remediation (nCCR) for Treatment Resistant Late-Life Depression

基于神经可塑性的计算机认知疗法（nCCR）治疗难治性晚年抑郁症

• 批准号: 10612341
• 负责人: Sarah Shizuko Morimoto
• 金额: $ 146.91万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612341
• 关键词: Address; Adopted; Adoption; Affective; Animal Model; Animals; Anterior; Antidepressive Agents; Attention; Behavioral; Brain; California; Cerebrum; Clinical; Clinical Trials; Clinical Trials Design; Cognitive; Cognitive deficits; Cognitive remediation; Communities; Computational algorithm; Corpus striatum structure; Data; Data Analytics; Disease; Disease remission; Doctor of Philosophy; Dorsal; Dose; Double-Blind Method; Elderly; Emerging Technologies; Evidence based treatment; Future; Health Care Costs; Impaired cognition; Impairment; Internet; Intervention; Learning; Major Depressive Disorder; Measures; Mediating; Mediation; Medical; Mental Depression; Methodology; Methods; Modeling; Moods; Multicenter Trials; National Institute of Mental Health; Neurobiology; Neuronal Plasticity; Norepinephrine; Outcome; Parietal Lobe; Participant; Patients; Performance; Pharmaceutical Preparations; Prefrontal Cortex; Procedures; Process; Public Health; Randomized; Relapse; Research Domain Criteria; Resistance; Rewards; Risk; Sampling; Science; Selective Serotonin Reuptake Inhibitor; Semantics; Serotonin; Site; Structure; Suicide; System; Technology; Testing; Therapeutic; Training; Translating; Utah; Verbal Learning; Work; active control; affective neuroscience; aging brain; behavior measurement; cingulate cortex; cognitive control; cognitive neuroscience; cognitive training; computerized; confirmatory trial; cost effective; depressive symptoms; design; digital medicine; digital tool; disability; dosage; effectiveness trial; experience; flexibility; functional improvement; geriatric depression; geriatric major depression; high risk; improved; indexing; inhibitor; iterative design; model design; mortality; multisensory; novel; older patient; recruit; response; reuptake; suicidal; suicidal risk; symptomatic improvement; theories; therapy resistant; treatment as usual; treatment group

Abstract This proposal is submitted in response to RFA-MH-18-707 and NOT-MH-20-027, and aims to conduct a randomized, double-blind, controlled confirmatory efficacy trial of a novel, neuroplasticity-based computerized cognitive remediation (nCCR) intervention for treatment resistant late-life major depressive disorder (LLD). We developed nCCR to target cognitive control deficits (CCD), a behavioral expression of altered function of the Research Domain Criteria (RDoC)-defined, cognitive control network (CCN). This novel intervention is consistent with NIMH priorities to advance interventions informed by cognitive and affective neuroscience (strategy 3.1) that can be disseminated to the community (strategy 3.3). In LLD, deficits in cognitive control functions (CCD) are common, and disabling. We and others have documented that specific CCD, and their underlying brain network abnormalities, are associated with poor response to antidepressants, relapse, and increased risk for suicide. These deficits are mediated by the CCN, a frontoparietal circuit that comprises the dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, and posterior parietal cortex, as well as projections to the ventromedial prefrontal cortex and subcortical structures, including the striatum. The theory guiding neuroplasticity-based cognitive interventions is that network abnormalities associated with negative disease-specific clinical outcomes can be altered through the induction of neuroplasticity (even in the aging brain), resulting in enhanced functioning of the target network, and symptomatic improvements. The methodology we employed is founded in basic animal science of induction of plasticity in the aging brain, and it is translated into computer algorithms that deliver (1) increasingly challenging; (2) dynamic difficulty adjusted; (3) attention demanding; and (4) immediately rewarding cognitive training designed to activate CCD associated with poor clinical outcomes. We recently tested nCCR in three preliminary clinical trials. Our preliminary data indicate that nCCR will likely engage our proposed target, CCD. Further, nCCR appears to have more robust mood effects in participants who have pronounced CCD, while SSRI/SNRI- treated patients are two times less likely to benefit. We designed nCCR to be: short (4-week dose), efficacious, mobile (available via web), cost-effective (does not require an MD/PhD), with the potential for wide distribution, easy adoptability, and extensibility to address this urgent, unmet therapeutic need in LLD. For these patients there is currently no treatment that adequately addresses both mood and cognitive impairment. The data produced by this proposal will allow us to study the relationship between CCD and changes in mood, and compare these effects to a control condition in LLD participants who have failed first-line treatments. Further, we propose a two-site, sufficiently powered trial to study our technology-facilitated parameters, as well as implementation procedures in two large medical systems, which have great potential to inform future interventions of this type and support scalability of mobile nCCR into “usual care” settings.

抽象的 该建议是根据RFA-MH-18-707和非MH-20-027提交的，旨在进行 新型，神经塑性计算机化的随机，双盲，受控的确认效率试验 耐治疗后期重大抑郁症（LLD）的认知补救（NCCR）干预措施。我们 开发了靶向认知控制定义的NCCR（CCD），这是一种行为表达的行为表达 研究领域标准（RDOC）定义，认知控制网络（CCN）。这种新颖的干预是 与NIMH优先级一致，以提高认知和情感神经科学所告知的干预措施 （策略3.1）可以将其传播到社区（策略3.3）。在LLD中，在认知控制中定义 函数（CCD）很常见，并且残疾。我们和其他人已经记录了特定的CCD及其 潜在的大脑网络异常，与对抗抑郁药，退休和 自杀的风险增加。这些定义是由CCN介导的，CCN是一个额叶电路，包括 负质额叶皮层，背扣带皮质和后顶叶皮层，以及 对腹侧前额叶皮层和皮质下结构的投影，包括纹状体。 基于神经塑性的理论指导性认知干预措施是网络异常相关的 通过诱导神经可塑性，可以改变具有阴性疾病特异性临床结果（即使在 衰老的大脑），导致目标网络功能增强以及有症状的改善。 我们采用的方法是基于基本动物科学的诱导衰老大脑的可塑性，以及 它被转化为计算机算法，这些算法（1）越来越挑战； （2）动态困难调整； （3）要求注意； （4）立即奖励旨在激活CCD相关的认知培训 临床结果不佳。我们最近在三项初步临床试验中测试了NCCR。 我们的初步数据表明NCCR可能会与我们提出的目标CCD相关。此外，NCCR 在发音CCD的参与者中似乎具有更大的情绪影响，而SSRI/SNRI- 治疗患者受益的可能性降低了两倍。我们将NCCR设计为：短（4周剂量），高效， 移动（通过Web获得），具有成本效益（不需要MD/PHD），具有广泛分发的潜力， 易于的可采用性和可扩展性，以满足LLD的这种紧急，未满足的治疗需求。对于这些患者 目前尚无适当解决情绪和认知障碍的治疗方法。数据 该提案产生的将使我们能够研究CCD与情绪变化之间的关系，以及 将这些效果与一线治疗失败的LLD参与者中的控制条件进行比较。更远， 我们提出了一个两个站点，足够的动力试验，以研究我们的技术知识参数以及 在两个大型医疗系统中的实施程序，它们具有巨大的潜力来告知未来 这种类型的干预措施并支持移动NCCR的可扩展性在“通常的护理”设置中。