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

项目摘要：创伤后应激障碍(PTSD)是一种常见的神经精神障碍，具有 据估计，美国的终生流行率约为8%。与战斗相关的创伤后应激障碍，一种特定类型的 高达25%的退伍军人患有创伤后应激障碍，这些退伍军人曾参加过战斗，对治疗反应较差。 在过去的二十年里，在理解糖尿病的病理生理学方面取得了重大进展。 创伤后应激障碍，其中大部分表明前额叶皮质的低代谢在创伤后应激障碍中起主要作用 情绪和认知的神经回路。虽然目前还不可能提供完全的治疗方法 解决创伤后应激障碍症状，重要的是开发针对前额叶的创新干预措施 直接进行低代谢，以改善创伤后应激障碍所固有的认知和情绪障碍。 针对前额叶皮质的经颅红外激光刺激(TILS)是一种非侵入性、非创伤性的治疗方法. 药理、便携、方便、经济实惠的光生物调节形式。TILs的作用机制 依赖于细胞色素c氧化酶(CCO)的光激活，CCO是线粒体呼吸的末端酶 催化氧还原以促进能量代谢的链。这种光子学-生物能量学机制 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现了两种光学神经成像方式，即宽带近距离 红外光谱(BbNIRS)和功能近红外光谱(FNIRS)，以直接和 定量评估TIL期间体内代谢/CCO的变化并成像异常的前额叶活动 患有创伤后应激障碍的退伍军人。两种创新的光学神经成像方式的使用，以及前景看好的 初步结果，为我们通过临床试验设计进一步推进创伤后应激障碍的研究提供了坚实的基础 严格测试TILs作为一种治疗创伤后应激障碍的新型、非侵入性和非药物干预措施。具体来说，我们 在一项在患有创伤后应激障碍的战斗暴露退伍军人中进行的两阶段研究中提出的建议，以1)阐明 TIL的病理生理机制和R61期的最佳治疗剂量；2) 在R33期应用TILs治疗认知和情绪障碍。我们假设TILs可以 系统地参与并上调前额叶皮质的氧代谢和功能活动， 导致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的改善。 该项目的结果将确定TILs是否作为一种新的、非侵入性的、非药理学的 成本效益高的疗法可以用来改善认知和情绪障碍，和/或整体症状 与战斗相关的创伤后应激障碍的严重性。

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.