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

项目概述：创伤后应激障碍（PTSD）是一种常见的神经精神障碍， 在美利坚合众国，估计终生流行率约为8%。战斗相关的创伤后应激障碍，一种特殊类型的 创伤后应激障碍，是发现在高达25%的战争退伍军人谁一直在战斗中，是对治疗的反应较低。 在过去的二十年里，在理解脑梗死的病理生理学方面取得了重大进展。 创伤后应激障碍，其中大部分表明，在前额叶皮层代谢低下发挥了重要作用，在中断 情绪和认知的神经回路虽然目前还不可能提供一种治疗方法， 为了解决创伤后应激障碍症状，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。 经颅红外激光刺激（TILS）针对前额叶皮层是一种非侵入性，非侵入性， 药理学的、便携的、方便的和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系统中的末端酶。 为能量代谢催化氧还原的链。这种光子学-生物能量学机制 通过刺激氧代谢对神经元产生独特的功能益处。 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），以直接和 定量评估TILS期间体内代谢/CCO变化，并对TILS患者的异常前额活动进行成像。 有创伤后应激障碍的退伍军人使用两种创新的光学神经成像模式，沿着有前途的 初步结果，为我们通过临床试验设计进一步推进PTSD的研究提供了坚实的基础 严格测试TILS作为一种新型的，非侵入性的，非药物干预PTSD。我们特别 在一项对患有创伤后应激障碍的退伍军人进行的双相研究中提出了一项建议，以1）阐明 TILS的病理生理机制，并确定R61期的最佳治疗剂量，以及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 系统地参与和上调前额叶皮层的氧代谢和功能活动， 从而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。 本项目的结果将确定TILS作为一种新型的、非侵入性的、非药物性的 并且具有成本效益的治疗可用于改善认知和情绪功能障碍和/或总体症状 与战斗有关的创伤后应激障碍

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.