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

有认知缺陷的退伍军人代表了退伍军人的大量服务和财政负担 管理（VA）。重要的是，即使接受治疗，这些退伍军人也有严重的社区问题。 整合，定义为恢复充分参与主要生活角色的能力（例如，有竞争力的就业， 学校和支持性的社会/家庭网络。VA中两个最突出的患者群体， 有认知缺陷和社区融合不良的是那些精神分裂症（SCZ）和脑外伤 创伤（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， 认知的关键细胞机制。重要的是，一些专门的心理和神经刺激 (e.g.,最近出现了针对神经可塑性和认知的治疗。新的神经可塑性- 有针对性的干预措施，改善导致SCZ社区融合不良的认知缺陷， TBI对VA医疗保健系统非常有价值。然而，为了评估这种新的疗效， 干预方法，我们需要客观的生物标志物措施，有效地评估神经可塑性， 适用于这些人群的临床试验。这些工具目前还不存在。这项建议是 旨在解决这一关键的治疗开发先决条件。该提案将采用一种 方法和使用基于神经科学的方法来客观评估非侵入性神经可塑性措施 在患有认知障碍（精神分裂症和TBI）的退伍军人中， 认知和社区融合的措施。 鉴于这些脑电图（EEG）测量神经可塑性的高度新颖的应用， 在SCZ和TBI的研究中，我们选择了SPiRE小型试点项目机制。本研究针对本项目 使用非侵入性EEG测量短时程（STP）和长时程增强（LTP），以：1）评估 招募有认知缺陷（TBI和SCZ）的退伍军人的可行性，检查基于EEG的 神经可塑性的措施，并优化范式，和2）评估的统计特性， 神经可塑性的措施，必要的步骤，以确定他们是否会被接受，作为 生物标志物。在一个探索性的目标，我们将评估神经可塑性措施之间的关系， 认知和社区融合。我们将利用从神经科学研究中翻译出来的范例， 客观评估神经可塑性的神经生理学指标。在拟议的2年研究中，我们将招募 共75名退伍军人（25名精神分裂症患者，25名TBI患者和25名无认知缺陷的健康退伍军人） 来自退伍军人管理局大洛杉矶医疗系统。 通过确定神经可塑性作为认知和社区整合的关键决定因素的作用， 患有认知障碍的退伍军人（即，精神分裂症或TBI），我们将解决大量的知识差距， 退伍军人社区融合不良的根本原因，使非常沉重的治疗和财政 对国家体制的要求。该项目将有助于评估神经可塑性的客观生物标志物， 可以用来衡量未来研究中针对认知的干预措施的有效性。结果是 这项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 有认知障碍

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.