Transcranial laser stimulation of prefrontal metabolism in post-traumatic stress disorder

经颅激光刺激创伤后应激障碍前额叶代谢

• 批准号: 9537694
• 负责人: Fenghua Tian
• 金额: $ 19.09万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-10-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9537694
• 关键词: Adverse effects; Americas; Attention; Bioenergetics; Clinical Trials; Clinical Trials Design; Cognition; Cognitive; Comorbidity; DSM-V; Energy Metabolism; Enzymes; Evaluation; Foundations; Functional disorder; Human; Image; Imaging Techniques; Impaired cognition; Intervention; Lasers; Memory; Metabolic; Metabolism; Mitochondria; Modality; Moods; Near-Infrared Spectroscopy; Neurons; Neuropsychological Tests; Optics; Outcome; Oxygen; Phase; Placebos; Play; Post-Traumatic Stress Disorders; Prefrontal Cortex; Prevalence; Randomized; Research; Resolution; Respiratory Chain; Role; Severities; Solid; Standardization; Symptoms; Testing; Therapeutic; Therapeutic Studies; United States; Veterans; War; associated symptom; cognitive enhancement; cognitive function; cohort; combat; cost effective; cytochrome c oxidase; disturbance in affect; dosage; effective therapy; executive function; hemodynamics; improved; in vivo; innovation; instrument; neural circuit; neuroimaging; neuropsychiatric disorder; novel; optical imaging; optimal treatments; photoactivation; photobiomodulation; photonics; portability; post intervention; psychiatric symptom; recruit; relating to nervous system; response; sham-controlled study; symptom cluster

Project Summary: Post-traumatic stress disorder (PTSD) is a common neuropsychiatric disorder with an estimated lifetime prevalence of ~8% in the United States of America. Combat-related PTSD, a specific type of PTSD, is found in up to 25% of war veterans who have been in combat and is less responsive to treatment. Over the past two decades, significant progress has been made in understanding the pathophysiology of PTSD, much of which indicates that hypometabolism in the prefrontal cortex plays a major role in the disrupted neural circuitry of mood and cognition. While it is not possible at present to offer a treatment for complete resolution of PTSD symptoms, it is important to develop innovative interventions targeting prefrontal hypometabolism directly in order to improve the cognitive and mood dysfunction inherent in PTSD. Transcranial infrared laser stimulation (TILS) directed at the prefrontal cortex is a non-invasive, non- pharmacologic, portable, convenient, and cost-effective form of photobiomodulation. The mechanism of TILS relies on photoactivation of cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial respiratory chain that catalyzes the reduction of oxygen for energy metabolism. This photonics-bioenergetics mechanism results in unique functional benefits for neurons by stimulating oxygen metabolism. Our research team has implemented two optical neuroimaging modalities, namely broadband near- infrared spectroscopy (bbNIRS) and functional near-infrared spectroscopy (fNIRS), to directly and quantitatively assess in vivo metabolic/CCO changes during TILS and image the abnormal prefrontal activity in in veterans with PTSD. The use of two innovative optical neuroimaging modalities, along with the promising preliminary results, provides us a solid foundation to further advance studies of PTSD via a clinical trial design to rigorously test TILS as a novel, non-invasive, and non-pharmacologic intervention for PTSD. Specifically, we proposal in a biphasic study among combat-exposed veterans with PTSD in order to 1) elucidate the pathophysiological mechanism of TILS and determine the optimal treatment dosage in the R61 phase, and 2) apply TILS to treat cognitive and mood dysfunction in the R33 phase. We hypothesize that TILS can systematically engage and up-regulate oxygen metabolism and functional activity in the prefrontal cortex, leading to improved cognitive and mood functioning as well as overall symptoms in veterans with PTSD. The outcome of this project will establish whether TILS as a novel, non-invasive, non-pharmacologic and cost-effective therapy can be used to ameliorate cognitive and mood dysfunction, and/or overall symptom severity in combat-related PTSD.

项目摘要：创伤后应激障碍（PTSD）是一种常见的神经精神疾病， 据估计，美国的终生患病率约为 8%。与战斗相关的创伤后应激障碍 (PTSD)，一种特定类型 高达 25% 的参战退伍军人患有创伤后应激障碍 (PTSD)，这些退伍军人对治疗反应较差。 在过去的二十年里，人们在理解疾病的病理生理学方面取得了重大进展。 PTSD，其中大部分表明前额叶皮层代谢低下在紊乱中起着重要作用 情绪和认知的神经回路。虽然目前还不可能提供完全治疗 为了解决 PTSD 症状，开发针对前额叶的创新干预措施非常重要 直接降低代谢，以改善 PTSD 固有的认知和情绪功能障碍。 针对前额皮质的经颅红外激光刺激 (TILS) 是一种非侵入性、非 药理学、便携式、方便且具有成本效益的光生物调节形式。 TILS的机制 依赖于细胞色素 C 氧化酶 (CCO) 的光活化，细胞色素 C 氧化酶是线粒体呼吸中的末端酶 催化能量代谢的氧还原的链。这种光子生物能机制 通过刺激氧代谢，为神经元带来独特的功能益处。 我们的研究团队已经实施了两种光学神经成像模式，即宽带近- 红外光谱（bbNIRS）和功能近红外光谱（fNIRS），直接和 定量评估 TILS 期间的体内代谢/CCO 变化并对异常前额叶活动进行成像 患有创伤后应激障碍 (PTSD) 的退伍军人。使用两种创新的光学神经成像模式，以及有前途的 初步结果为我们通过临床试验设计进一步推进 PTSD 研究奠定了坚实的基础 严格测试 TILS 作为一种针对 PTSD 的新型、非侵入性、非药物干预措施。具体来说，我们 建议对患有创伤后应激障碍 (PTSD) 的经历过战斗的退伍军人进行双相研究，以便 1) 阐明 TILS的病理生理机制并确定R61阶段的最佳治疗剂量，2) 应用TILS治疗R33期的认知和情绪功能障碍。我们假设 TILS 可以 系统地参与并上调前额皮质的氧代谢和功能活动， 改善患有创伤后应激障碍的退伍军人的认知和情绪功能以及整体症状。 该项目的结果将确定 TILS 是否作为一种新型、非侵入性、非药物疗法 经济有效的治疗可用于改善认知和情绪功能障碍，和/或整体症状 与战斗相关的创伤后应激障碍（PTSD）的严重程度。