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.

摘要