Use of a Novel Neuroplasticity-based Neurobehavioral Intervention for PTSD

描述（由申请人提供）： 创伤后应激障碍（PTSD）是一种严重的精神疾病，在退伍军人中很常见，而且往往是高度慢性的。创伤后应激障碍携带频繁的合并症，导致严重的功能障碍，并造成惊人的个人，社会和经济负担。PTSD的治疗结果，特别是在退伍军人群体中，通常很差。没有一致有效的替代方案，以主线的心理治疗干预，我们已经研究的神经相关性，在一个正在进行的研究，已被确定。因此，迫切需要开发新的治疗干预措施。与治疗PTSD相关的困难进一步由于与轻度创伤性脑损伤（mTBI）的共病而复杂化，所述轻度创伤性脑损伤是阿富汗和伊拉克冲突的"标志性损伤"，以及慢性疼痛。考虑这些合并症是很重要的，因为研究表明，PTSD，TBI和慢性疼痛共存的频率远远高于退伍军人中单独存在的频率。人们普遍认为，这些情况只会使治疗更加复杂。我的实验室和其他实验室的神经科学研究发现，执行控制过程在情绪和自我调节方面的缺陷是创伤后应激障碍的核心，沿着过度的负面情绪反应。我们已经在孤立的慢性疼痛患者中观察到类似的神经缺陷。同样，mTBI中的数据 还涉及执行功能和自我调节。这些发现表明，执行控制和负性情绪反应的改善可能会改善PTSD的核心缺陷及其主要并发症，mTBI和慢性疼痛。新兴的研究表明，支持执行功能的神经回路保持可塑性，其活动可以通过有针对性的基于神经可塑性的神经行为干预来增强，同样，负面情绪反应可以通过训练来减少。我们最近试行了一项神经行为干预措施，该措施是与行业合作伙伴合作开发的，旨在通过量身定制的、适应性强的、具有挑战性的计算机游戏训练，增加执行控制大脑网络的活动，减少负面情绪反应。这项试验的结果表明，这种基于神经可塑性的神经行为干预可能是PTSD患者以及共病mTBI和慢性疼痛的一种有前途的新型治疗干预-从而将有关PTSD的尖端神经科学知识转化为有针对性的治疗。我们的提案中使用的互联网提供的训练游戏非常吸引人，为治疗提供了一个很好的切入点，并允许在许多已经熟悉互联网和基于计算机的游戏的退伍军人中进行简单和具有成本效益的传播。我们将招募30名患有创伤后应激障碍的退伍军人。在基线时，患者的症状将（1）由经过培训的临床医生使用SCID、PTSD CAPS访谈和TBI和慢性疼痛的自我报告测量进行评估。然后，他们将（2）完成对自己情绪调节能力的自我报告测量，（3）使用我们最近发现在焦虑症患者中异常的情绪调节任务（包括创伤后应激障碍）以及其他涉及各种执行和情绪功能的任务进行基线行为和脑电图评估。然后将参与者（4）随机分配到两组（干预或控制游戏，NS = 15，分别）之一。干预组参与者将完成为期60天的基于神经可塑性的神经行为干预，而对照组参与者将完成为期60天的游戏，这些游戏旨在参与但不提供情绪调节益处。培训将通过互联网通过一个定制的网站利用我们现有的基础设施提供。将在培训后进行与基线相同的评估和扫描，并在3个月后进行最终临床随访。 公共卫生相关性： 创伤后应激障碍是一种严重的精神疾病，在退伍军人中很常见，通常是高度慢性的，经常伴有合并症，导致严重的功能障碍，并造成惊人的个人，社会和经济负担。患有PTSD的退伍军人的治疗结果通常很差。目前还没有确定可替代心理治疗干预主线的持续有效的替代方案。因此，迫切需要开发新的治疗方法。我们建议在这个试点项目中测试的基于神经可塑性的神经行为干预可能是PTSD患者的一种有前途的新治疗方法-从而将有关情感缺陷的尖端神经科学知识和PTSD的自我调节转化为增强这些功能的靶向治疗。此外，该计划中使用的互联网提供的训练游戏非常吸引人，为治疗提供了一个很好的切入点，并允许在许多已经熟悉互联网和基于计算机的游戏的退伍军人中进行简单和具有成本效益的传播。

DESCRIPTION (provided by applicant): Post-traumatic stress disorder (PTSD) is severe psychiatric disorder that is common amongst veterans, and often highly chronic. PTSD carries frequent comorbidities, causes significant functional impairment and poses staggering personal, societal and financial burdens. Treatment outcomes for PTSD, in particular in veteran populations, are generally poor. No consistently effective alternatives to the main line of psychotherapeutic interventions, which we are already studying the neural correlates of in an ongoing study, have been identified. Thus, there is a pressing clinical need for development of novel treatment interventions. The difficulties associated with treatment of PTSD are further compounded by comorbidity with mild traumatic brain injury (mTBI), which is the "signature injury" of the conflicts in Afghanistan and Iraq, as well as chronic pain. Considering these comorbidities is important, as studies have shown that the frequencies with which PTSD, TBI and chronic pain co-exist is considerably higher than the frequencies with which they exist in isolation in veterans. It is widely believed that these conditions only serve to further complicate treatment. Neuroscience studies from my lab and others' have found that deficits in the use of executive control processes for emotion- and self-regulation are central to PTSD, along with excessive negative emotional reactivity. We have observed similar neural deficits in patients with chronic pain in isolation. Likewise, data in mTBI also implicates executive functioning and self-regulation. These findings suggest that improvements in executive control and negative emotional reactivity may ameliorate core deficits in PTSD, and its major co- morbidities, mTBI and chronic pain. Emerging research suggests that the neural circuitry that supports executive functions remains plastic and that its activity can be boosted with targeted neuroplasticity-based neurobehavioral interventions, and likewise that negative emotional reactivity can be diminished with training. We recently piloted a neurobehavioral intervention, developed in collaboration with industry partners, aimed at increasing activity in an executive control brain network and diminishing negative emotional reactivity through training with tailored, adaptive and challenging computer-based games. The results of this pilot suggest that this neuroplasticity-based neurobehavioral intervention may be a promising novel treatment intervention for patients with PTSD as well as comorbid mTBI and chronic pain - thus translating cutting-edge neuroscience knowledge about PTSD into a targeted treatment. The internet-delivered training games used in our proposal are very engaging, provide an excellent entry point for treatment, and allow for easy and cost-effective dissemination amongst the many veterans already comfortable with internet- and computer-based games. Wewill recruit 30 veterans with PTSD. At baseline, patients' symptoms will be (1) assessed by a trained clinician using the SCID, PTSD CAPS interview and self-report measures of TBI and chronic pain. They will then (2) complete self-report measurements of their emotion-regulatory abilities, and (3) undergo baseline behavioral and EEG assessments using an emotion regulation task that we have recently found to be abnormal in anxiety disorder patients, including PTSD, as well as other tasks tapping into a variety of executive and emotional functions. Participants will then (4) be randomly assigned to one of two groups (intervention or control games, Ns = 15, respectively). Intervention group participants will complete a 60-day neuroplasticity- based neurobehavioral intervention while control group participants will complete 60-days of games designed to be engaging but which provide no emotion-regulatory benefits. The training will be delivered through the internet via a custom-built website utilizing our existing infrastructure. Assessments and scans identical to those at baseline will be administered post-training, with final clinical follow-up 3 months later. PUBLIC HEALTH RELEVANCE: PTSD is severe psychiatric disorder that is common amongst veterans, often highly chronic, carries frequent comorbidities, causes significant functional impairment and poses staggering personal, societal and financial burdens. Treatment outcomes for veterans with PTSD are generally poor. No consistently effective alternatives to the main line of psychotherapeutic intervention have been identified. Thus, there is a pressing clinical need for development of new treatments. The neuroplasticity-based neurobehavioral intervention that we propose to test in this pilot project may be a promising novel treatment for patients with PTSD - thus translating cutting-edge neuroscience knowledge about deficits in emotion- and self-regulation in PTSD into a targeted treatment boosting these functions. Moreover, the internet-delivered training games used in this program are very engaging, provide an excellent entry point for treatment, and allow for easy and cost-effective dissemination amongst the many veterans already comfortable with internet- and computer-based games.