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

经颅激光刺激后创伤后应激障碍前额叶代谢

FENGHUA TIAN (2017-08-01 to 2019-07-31) $419,625

Project ID: R61MH113721 (NIMH)

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Abstract

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.

创伤后应激障碍（PTSD）是一种常见的神经精神疾病，估计在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）是一种特殊类型的创伤后应激障碍，在战斗中退伍军人中占多达25％，对治疗的反应较少。在过去的二十年中，在理解创伤后应激障碍的病理生理学方面取得了重大进展，其中大部分表明前额叶皮质中的代谢减退在情绪和认知的神经回路中起主要作用。虽然目前不可能提供完全解决PTSD症状的治疗方法，但重要的是开发直接针对前额叶代谢减退的创新干预措施，以改善创伤后应激障碍中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，非药物，便携，方便且经济的光生物调节形式。 TILS的机制依赖于细胞色素c氧化酶（CCO）的光活化，CCO是线粒体呼吸链中的末端酶，其催化能量代谢的氧还原。这种光子 - 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）和功能性近红外光谱（fNIRS），可直接和定量评估TILS期间的体内代谢/ CCO变化，并对异常的前额叶活动进行成像。创伤后应激障碍的退伍军人。使用两种创新的光学神经影像学方法，以及有希望的初步结果，为通过临床试验设计进一步推进PTSD研究以严格测试TILS作为一种新型，非侵入性和非药物干预提供了坚实的基础。创伤后应激障碍。具体而言，我们建议在具有PTSD的战斗暴露的退伍军人中进行双相研究，以便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治疗认知和情绪功能障碍。 R33阶段。我们假设TILS可以系统地参与和上调前额皮质中的氧代谢和功能活动，从而改善认知和情绪功能以及患有创伤后应激障碍的退伍军人的整体症状。该项目的结果将确定TILS是否可用于改善与战斗相关的创伤后应激障碍中的认知和情绪功能障碍和/或整体症状严重程度的新型，非侵入性，非药物和成本效益的治疗。