New Applications of Neuroplasticity Biomarkers in Veterans with Traumatic Brain Injury or Schizophrenia

神经可塑性生物标志物在患有创伤性脑损伤或精神分裂症的退伍军人中的新应用

• 批准号: 10451487
• 负责人: Jonathan Wynn
• 金额: --
• 依托单位: VA GREATER LOS ANGELES HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-11-01 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10451487
• 关键词: Address; Adopted; Animals; Area; Attention; Auditory; Biological Markers; Brain; Clinical Trials; Cognition; Cognition Disorders; Cognitive; Cognitive deficits; Cognitive remediation; Community Integration; Complex; Data; Disease; Electroencephalography; Emotions; Empathy; Employment; Environment; Etiology; Evaluation; Family; Financial Hardship; Frequencies; Future; Healthcare Systems; Human; Impaired cognition; Impairment; Independent Living; Individual; Intervention; Knowledge; Lead; Learning; Life; Link; Long-Term Potentiation; Los Angeles; Measures; Memory; Mental Health Services; Methods; Mind; Neurodevelopmental Disorder; Neuronal Plasticity; Neurosciences; Outcome; Participant; Patient Self-Report; Patients; Pattern; Pilot Projects; Plant Roots; Population; Process; Property; RQ2; Research; Resected; Role; Running; Sampling; Schizophrenia; Schools; Services; Social Network; Structure; System; Time; Tissues; Training; Translating; Traumatic Brain Injury; Treatment Cost; Treatment Efficacy; United States Department of Veterans Affairs; Veterans; Visual; Work; acceptability and feasibility; base; behavior measurement; clinical investigation; cognitive function; cognitive neuroscience; cognitive process; design; efficacy evaluation; experience; functional outcomes; improved; in vivo; neurophysiology; novel; poor communities; programs; psychopharmacologic; psychosocial; recruit; relating to nervous system; response; short-term potentiation; social; theories; therapy development; tool; translational approach

Veterans with cognitive deficits represent a substantial service and financial burden at the Veterans Administration (VA). Importantly, even with treatment, these Veterans have severe problems with community integration, defined as the ability to return to full participation in major life roles (e.g., competitive employment, school) and supportive social/family networks. Two of the most prominent patient groups within the VA who have cognitive deficits and poor community integration are those with schizophrenia (SCZ) and traumatic brain injury (TBI). There is strong evidence that both disorders are associated with impaired neuroplasticity, which is a key cellular mechanism of cognition. Importantly, several specialized psychosocial and neurostimulation (e.g., tDCS) treatments that target neuroplasticity and cognition have recently emerged. New neuroplasticity- focused interventions that improve the cognitive deficits that lead to poor community integration in SCZ and TBI would highly valuable for the VA healthcare system. However, to evaluate the efficacy of this novel intervention approach, we need objective biomarker measures that validly assess neuroplasticity and are appropriate for use in clinical trials in these populations. These tools currently do not exist. This proposal is designed to address this key treatment development prerequisite. This proposal will adopt a translational approach and use neuroscience-based methods to objectively assess non-invasive neuroplasticity measures in Veterans with cognitive disorders (schizophrenia and TBI) and examine relationships to behavioral measures of cognition and community integration. Given the highly novel application of these electroencephalography (EEG) measures of neuroplasticity to the study of SCZ and TBI, we selected the SPiRE small pilot project mechanism. The research aims for this project are to measure short-term (STP) and long-term potentiation (LTP) using non-invasive EEG to: 1) evaluate the feasibility of recruiting Veterans with cognitive deficits (TBI and SCZ), examine tolerability of the EEG-based neuroplasticity measures, and optimize the paradigms, and 2) evaluate the statistical properties of the neuroplasticity measures, a necessary step to determine whether they will be acceptable to serve as biomarkers. In an exploratory aim, we will evaluate the relationships between the neuroplasticity measures and cognition and community integration. We will utilize paradigms translated from neuroscience studies to objectively assess neurophysiological measures of neuroplasticity. In the proposed 2-year study we will recruit a total of 75 Veterans, (25 with schizophrenia, 25 with TBI, and 25 healthy Veterans without cognitive deficits) from the VA Greater Los Angeles Healthcare system. By identifying the role of neuroplasticity as a key determinant of cognition and community integration in Veterans with cognitive disorders (i.e., schizophrenia or TBI), we will address substantial knowledge gaps in the root causes of poor community integration in Veterans that make very heavy treatment and financial demands on the national VA system. This project will help assess objective biomarkers of neuroplasticity that can be used to gauge the efficacy of interventions targeting cognition in future studies. The results from this study will help guide interventions that ultimately are aimed at improving community integration in Veterans with cognitive disorders.

认知缺陷的退伍军人代表了退伍军人的实质性服务和经济负担 管理（VA）。重要的是，即使接受治疗，这些退伍军人在社区方面也有严重的问题 集成，被定义为能够充分参与主要生活角色的能力（例如，竞争性就业， 学校）和支持性的社会/家庭网络。 VA中最杰出的两个患者群体中的两个 具有认知缺陷和社区融合不佳的是精神分裂症（SCZ）和大脑创伤的人 受伤（TBI）。有强有力的证据表明，这两种疾病都与神经可塑性受损有关，即 认知的关键细胞机制。重要的是，一些专业的社会心理和神经刺激 （例如，TDC）最近出现了针对神经可塑性和认知的治疗方法。新的神经可塑性 - 重点干预措施，改善了导致SCZ和SCZ社区融合不佳的认知缺陷 TBI对于VA医疗保健系统非常有价值。但是，要评估这部小说的功效 干预方法，我们需要有效评估神经塑性的客观生物标志物措施 适用于这些人群中的临床试验。这些工具当前不存在。该提议是 旨在解决此关键治疗开发的先决条件。该建议将采用翻译 方法并使用基于神经科学的方法来客观地评估非侵入性神经塑性度量 在认知障碍（精神分裂症和TBI）的退伍军人中，检查与行为的关系 认知和社区融合的度量。 鉴于这些脑电图（EEG）的高度新颖应用神经可塑性的测量 SCZ和TBI的研究，我们选择了小型试点项目机制。研究目的是该项目 使用非侵入性脑电图测量短期（STP）和长期增强（LTP） 具有认知缺陷（TBI和SCZ）招募退伍军人的可行性，检查基于EEG的耐受性 神经可塑性度量和优化范例，2）评估 神经塑性措施，确定它们是否可以接受的必要步骤 生物标志物。在探索性目的中，我们将评估神经可塑性度量与 认知和社区融合。我们将利用从神经科学研究翻译成的范式 客观地评估神经塑性的神经生理学测量。在拟议的两年研究中，我们将招募 共有75名退伍军人（25例精神分裂症，25例TBI和25名没有认知缺陷的健康退伍军人） 来自VA大洛杉矶医疗保健系统。 通过确定神经可塑性作为认知和社区融合的关键决定因素 患有认知障碍的退伍军人（即精神分裂症或TBI），我们将解决巨大的知识差距 退伍军人社区融合不力的根本原因，这些退伍军人进行了非常重的待遇和财务 对国家VA系统的需求。该项目将有助于评估神经可塑性的客观生物标志物 可以用来评估针对认知的干预措施在未来的研究中的疗效。从中的结果 研究将有助于指导干预措施，最终旨在改善退伍军人的社区融合 患有认知障碍。