检索问题
经颅 光 生物 调节
经颅光生物调节 (Transcranial Photobiomodulation, tPBM) 是一种新兴的非侵入性神经刺激技术，它利用红光到近红外 (NIR) 光照射大脑，以治疗多种神经和心理疾病，并改善认知功能 。
作用机制
tPBM 的主要作用机制涉及光线对细胞内线粒体的刺激：
- 线粒体功能增强：红光/NIR 光能够刺激线粒体呼吸链中的细胞色素 c 氧化酶 (complex IV)，从而增加三磷酸腺苷 (ATP) 的合成 。ATP 是细胞的能量货币，其增加有助于增强神经元的代谢能力 。
- 离子通道激活与基因表达：光线吸收也会激活离子通道，导致钙离子释放，进而激活转录因子和基因表达 。
- 神经保护和修复：tPBM 能够刺激抗炎、抗凋亡和抗氧化反应，同时促进神经发生和突触形成 。这些机制共同作用，有助于保护神经元免受损伤，并促进神经系统的修复和再生 。
- 改善脑血流和氧合：NIR 光被证明能显著增加脑血流量和组织氧合，从而改善大脑功能 。
治疗应用
tPBM 在多种神经认知和神经精神疾病中显示出潜力：
-
神经退行性疾病：
- 阿尔茨海默病 (AD) 和轻度认知障碍 (MCI)：tPBM 被认为是治疗 AD 和 MCI 的有前景的方法 。研究发现，tPBM 能改善 AD 引起的 MCI 患者的认知功能，例如蒙特利尔认知评估量表 (K-MoCA) 分数在治疗组显著提高，并且没有报告严重不良事件，表明其作为家庭使用干预措施的有效性和安全性 。
- 帕金森病 (PD)：tPBM 在 PD 的治疗中也引起了越来越多的关注 。
- 概述：神经退行性疾病涉及中枢神经元进行性功能障碍和损失，目前缺乏有效的方法来阻止或逆转其进展 。tPBM 作为一种非侵入性物理疗法，通过刺激、愈合、再生和保护受损或退化的组织，展现出缓解这些疾病的潜力，从而提高患者的生活质量 。
-
脑损伤：
- 创伤性脑损伤 (TBI)：tPBM 对急性或慢性 TBI 患者有益 。在轻度 TBI (mTBI) 患者中进行的随机安慰剂对照试验显示，tPBM 显著改善了视觉工作记忆表现、言语记忆学习、主观睡眠质量、身体脑震荡后症状、疼痛强度和创伤后应激障碍 (PTSD) 症状 。功能性磁共振成像 (fMRI) 也显示 tPBM 能调节 TBI 中可能受损的内在脑网络（默认模式网络和显著性网络）的激活 。
- 中风：tPBM 在中风治疗中也受到关注 。尽管早期的 NEST 临床试验未能证明光疗在中风患者中的疗效，但仍有许多未解决的问题和经验教训，未来的研究可能关注更优化的刺激参数、剂量和患者选择标准 。
-
情绪障碍：
- 抑郁症：tPBM 被探索作为重度抑郁症 (MDD) 的一种创新治疗方法 。一项荟萃分析发现，tPBM 在减轻抑郁症状严重程度方面可能有效，尤其是在 MDD 患者的单臂研究中显示出显著效果 。然而，针对双盲、假对照研究的荟萃分析未能支持 tPBM 优于假治疗的显著统计学优势，这可能与样本量偏差有关，需要更大规模的随机、假对照研究来充分证明其抗抑郁疗效和确定最佳剂量参数 。
- 焦虑症：一项研究表明，使用 945-nm LED 进行 tPBM 可以改善脑活动，并可能在临床上减少大学生的焦虑和抑郁 。
- 青少年情绪障碍：tPBM 也被纳入青少年情绪障碍的补充和综合医学治疗方法综述中 。
-
认知功能改善：
- 健康老年人：tPBM 已显示出改善老年人认知功能的潜力 。一项研究发现，与假 tPBM 相比，主动 tPBM 显著改善了健康老年人 3-back 任务的准确性和反应时间，并通过优化静息态功能脑网络特性（如整体效率、局部效率、节点效率和功能连接）来实现 。特别是，左前额叶皮层的功能连接和节点效率的变化与 3-back 准确性的改善呈正相关 。
- 健康个体：tPBM 甚至可以增强健康个体的认知功能 。
-
Rett 综合征 (RTT)：
- tPBM 被提出作为 Rett 综合征的辅助治疗方法，这是一种严重的 X 连锁神经发育障碍。tPBM 的生物能量、氧化还原、抗炎和神经营养作用与 RTT 的关键细胞机制（如线粒体功能障碍、氧化应激、神经炎症和突触可塑性受损）的收敛性，表明 tPBM 可能部分补偿 RTT 中的生物能量和信号异常，作为一种多靶点、病理生理学知情的神经调节策略 。
光照参数和递送方法
tPBM 通常使用红光到近红外 (NIR) 光，波长范围为 600-1100 nm ，NIR 光的具体范围通常指 800 至 2,500 nm 的波长 。激光或发光二极管 (LED) 都可用作光源 。
挑战与局限性
- 光线穿透深度：经颅 PBM 的主要挑战是光线穿透组织的指数衰减，难以将足够的剂量传递到深层脑区以实现最佳刺激 。为了克服这一限制，已提出颅内和鼻内光线递送方法作为替代方案 。
- 最佳剂量和参数：尽管许多非对照研究表明 tPBM 对 MDD 有效，但其最佳剂量仍待确定 。对于其他神经系统疾病，也需要进行剂量探索研究以确定最佳 tPBM 参数 。
- 研究证据强度：尽管存在大量临床前和初步临床证据，但在某些领域，特别是针对抑郁症，双盲、假对照研究的证据强度相对较弱，需要更大规模的随机对照试验来验证其疗效 。
安全性
tPBM 通常被认为是安全的非侵入性治疗方法 。一项研究调查了 1064 nm 激光 tPBM 在健康人脑安全性方面的综合定量研究，结果显示 tPBM 不会引起脑结构或功能的显著变化，也不会损害认知能力，且具有良好的耐受性，例如在疲劳、瘙痒、疼痛、灼热、温暖、头晕和嗜睡方面的不适感极小 。没有观察到灰质、白质或脑脊液体积或密度的显著变化，也没有神经元损伤的迹象（神经元特异性烯醇化酶或 S100β 水平没有增加） 。
未来展望
tPBM 作为一个“广谱、毒性更小、非侵入性”的治疗方案，在神经退行性疾病的治疗中具有巨大潜力 。它为神经科学领域提供了新的突破性治疗方法，有望通过多种策略改善认知功能 。未来的研究需要进一步验证现有发现，探索更有效的递送方法，并优化治疗参数，以使其成为主流治疗方式，甚至开发针对高危个体的预防性疗法 。
References
1Brain Photobiomodulation Therapy: a Narrative Review.PubMed
Farzad Salehpour, Javad Mahmoudi, Farzin Kamari, et al.
Mol Neurobiol. 2018 Aug;55(8):6601-6636. doi: 10.1007/s12035-017-0852-4. Epub 2018 Jan 11.
Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is an innovative treatment for a wide range of neurological and psychological conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover, light absorption by ion channels results in release of Ca and leads to activation of transcription factors and gene expression. Brain PBM therapy enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti-apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis. Its therapeutic role in disorders such as dementia and Parkinson's disease, as well as to treat stroke, brain trauma, and depression has gained increasing interest. In the transcranial PBM approach, delivering a sufficient dose to achieve optimal stimulation is challenging due to exponential attenuation of light penetration in tissue. Alternative approaches such as intracranial and intranasal light delivery methods have been suggested to overcome this limitation. This article reviews the state-of-the-art preclinical and clinical evidence regarding the efficacy of brain PBM therapy.
2Transcranial Photobiomodulation in Rett Syndrome: A Mechanistic Review and Therapeutic Hypothesis.PubMed
Fabio Luchese, Carlos Lohmann, Borja Ignacio Ferreras, et al.
Photobiomodul Photomed Laser Surg. 2026 Mar;44(3):157-167. doi: 10.1177/25785478251415480. Epub 2026 Feb 9.
OBJECTIVE: To propose a mechanistic framework for the use of transcranial photobiomodulation (tPBM) as an adjunctive treatment in Rett syndrome (RTT). BACKGROUND DATA: RTT is a severe X-linked neurodevelopmental disorder caused mainly by MECP2 variants, with limited disease-modifying therapies. tPBM delivers red-to-near-infrared light to the brain and shows promising effects in several neurocognitive and neuropsychiatric conditions. METHODS: We reviewed key cellular mechanisms of RTT, namely mitochondrial dysfunction, oxidative stress, neuroinflammation, and impaired synaptic plasticity, and summarized established bioenergetic, redox, anti-inflammatory, and neurotrophic actions of tPBM. RESULTS: The convergence between these pathways suggests that tPBM could partially compensate for bioenergetic and signaling abnormalities in RTT, acting as a multi-target, pathophysiology-informed neuromodulation strategy. CONCLUSIONS: Although speculative, this mechanistic convergence supports prioritizing preclinical studies in Mecp2-deficient models and early-phase feasibility trials of tPBM in individuals with RTT.
3Transcranial photobiomodulation improves functional brain networks and working memory in healthy older adults: An fNIRS study.PubMed
Qin Yang, Xiujuan Qu, Can Sheng, et al.
Neuroimage. 2025 Aug 1;316:121305. doi: 10.1016/j.neuroimage.2025.121305. Epub 2025 Jun 6.
BACKGROUND: Transcranial photobiomodulation (tPBM), as a novel non-invasive neurostimulation technique, has shown the compelling potential for improving cognitive function in aging population. However, the potential mechanism remains unclear. Neuroimaging studies have found that tPBM-induced physiological changes exist in both targeted and non-targeted brain areas, suggesting the necessity of understanding the modulation mechanism from the perspective of the whole brain level. OBJECTIVE: This randomized, single-blind, sham-controlled crossover study aimed to investigate the hypothesis that tPBM improved working memory in healthy older adults through the mechanism of optimizing the properties of the resting-state functional brain networks. METHODS: A total of 55 right-handed healthy older adults were randomly assigned to sham tPBM session group or active tPBM session group. After a washout interval, they were assigned to the opposite intervention session. Each session included the following: active or sham tPBM application with a 1064-nm laser to the left forehead; before and after, resting-state functional near-infrared spectroscopy (fNIRS) measurements; and the digital n-back task. Differences in accuracy and reaction time of the n-back task, and changes in functional connectivity and graph metrics of the brain networks were investigated and compared between the active and sham tPBM sessions. In addition, correlations between tPBM-induced changes in functional brain networks, and the n-back task were examined. RESULTS: The results showed that compared with the sham tPBM session, the accuracy and reaction time during 3-back task significantly improved in the active tPBM session. In addition, the global efficiency, local efficiency, nodal efficiency, and functional connectivity significantly increased in the active tPBM session, particularly in the frontoparietal areas. Importantly, the altered 3-back accuracy was positively correlated with the changes of functional connectivity and nodal efficiency mainly in left prefrontal cortex in those who had increased 3-back accuracy in the active tPBM session. CONCLUSION: This study suggests that tPBM may serve as an effective tool to improve working memory in older adults through the modulation of resting-state functional brain network properties. Investigations in large-scale samples are needed to further validate the findings of this study.
4Near Infrared (NIR) Light Therapy of Eye Diseases: A Review.PubMed
Qin Zhu, Shuyuan Xiao, Zhijuan Hua, et al.
Int J Med Sci. 2021 Jan 1;18(1):109-119. doi: 10.7150/ijms.52980. eCollection 2021.
Near infrared (NIR) light therapy, or photobiomodulation therapy (PBMT), has gained persistent worldwide attention in recent years as a new novel scientific approach for therapeutic applications in ophthalmology. This ongoing therapeutic adoption of NIR therapy is largely propelled by significant advances in the fields of photobiology and bioenergetics, such as the discovery of photoneuromodulation by cytochrome c oxidase and the elucidation of therapeutic biochemical processes. Upon transcranial delivery, NIR light has been shown to significantly increase cytochrome oxidase and superoxide dismutase activities which suggests its role in inducing metabolic and antioxidant beneficial effects. Furthermore, NIR light may also boost cerebral blood flow and cognitive functions in humans without adverse effects. In this review, we highlight the value of NIR therapy as a novel paradigm for treatment of visual and neurological conditions, and provide scientific evidence to support the use of NIR therapy with emphasis on molecular and cellular mechanisms in eye diseases.
5Photobiomodulation for Neurodegenerative Diseases: A Scoping Review.PubMed
Qi Shen, Haoyun Guo, Yihua Yan
Int J Mol Sci. 2024 Jan 28;25(3):1625. doi: 10.3390/ijms25031625.
Neurodegenerative diseases involve the progressive dysfunction and loss of neurons in the central nervous system and thus present a significant challenge due to the absence of effective therapies for halting or reversing their progression. Based on the characteristics of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), which have prolonged incubation periods and protracted courses, exploring non-invasive physical therapy methods is essential for alleviating such diseases and ensuring that patients have an improved quality of life. Photobiomodulation (PBM) uses red and infrared light for therapeutic benefits and functions by stimulating, healing, regenerating, and protecting organizations at risk of injury, degradation, or death. Over the last two decades, PBM has gained widespread recognition as a non-invasive physical therapy method, showing efficacy in pain relief, anti-inflammatory responses, and tissue regeneration. Its application has expanded into the fields of neurology and psychiatry, where extensive research has been conducted. This paper presents a review and evaluation of studies investigating PBM in neurodegenerative diseases, with a specific emphasis on recent applications in AD and PD treatment for both animal and human subjects. Molecular mechanisms related to neuron damage and cognitive impairment are scrutinized, offering valuable insights into PBM's potential as a non-invasive therapeutic strategy.
7Transcranial near-infrared light in treatment of neurodegenerative diseases.PubMed
Damir Nizamutdinov, Chibueze Ezeudu, Erxi Wu, et al.
Front Pharmacol. 2022 Aug 8;13:965788. doi: 10.3389/fphar.2022.965788. eCollection 2022.
Light is a natural agent consisting of a range of visible and invisible electromagnetic spectrum travels in waves. Near-infrared (NIR) light refers to wavelengths from 800 to 2,500 nm. It is an invisible spectrum to naked eyes and can penetrate through soft and hard tissues into deep structures of the human body at specific wavelengths. NIR light may carry different energy levels depending on the intensity of emitted light and therapeutic spectrum (wavelength). Stimulation with NIR light can activate intracellular cascades of biochemical reactions with local short- and long-term positive effects. These properties of NIR light are employed in photobiomodulation (PBM) therapy, have been linked to treating several brain pathologies, and are attracting more scientific attention in biomedicine. Transcranial brain stimulations with NIR light PBM in recent animal and human studies revealed a positive impact of treatment on the progression and improvement of neurodegenerative processes, management of brain energy metabolism, and regulation of chronic brain inflammation associated with various conditions, including traumatic brain injury. This scientific overview incorporates the most recent cellular and functional findings in PBM with NIR light in treating neurodegenerative diseases, presents the discussion of the proposed mechanisms of action, and describes the benefits of this treatment in neuroprotection, cell preservation/detoxification, anti-inflammatory properties, and regulation of brain energy metabolism. This review will also discuss the novel aspects and pathophysiological role of the glymphatic and brain lymphatics system in treating neurodegenerative diseases with NIR light stimulations. Scientific evidence presented in this overview will support a combined effort in the scientific community to increase attention to the understudied NIR light area of research as a natural agent in the treatment of neurodegenerative diseases to promote more research and raise awareness of PBM in the treatment of brain disorders.
8Transcranial Photobiomodulation Improves Cognitive Function, Post-Concussion, and PTSD Symptoms in Mild Traumatic Brain Injury.PubMed
Tsz-Lok Lee, David Yuen-Chung Chan, Danny Tat-Ming Chan, et al.
J Neurotrauma. 2025 Oct;42(19-20):1695-1707. doi: 10.1089/neu.2025.0048. Epub 2025 Jun 9.
Traumatic brain injury (TBI) occurs in millions of people globally each year, with mild TBI (mTBI) representing over 90% of cases. Despite the common assumption of full recovery, significant disturbances persist in many patients with mTBI, including cognitive deficit, headache, dizziness, sleep problems, and symptoms of post-traumatic stress disorder (PTSD). Given that effective treatment is still scarce, the present study investigated the efficacy of transcranial photobiomodulation (tPBM) as an intervention for improving these sequelae in patients with mTBI. In this randomized placebo-controlled trial, 17 patients with mTBI were recruited. Participants were randomized to receive both real and sham tPBM conditions with a counterbalanced order, with a 1-week washout between interventions. Assessments were conducted at baseline, after real tPBM, and after sham tPBM. These included neuropsychological tests, measurements of oxygenated hemoglobin using functional near-infrared spectroscopy during a visual working memory task, and self-rated questionnaires assessing sleep quality, physical post-concussion symptoms, pain intensity, and PTSD symptoms. Compared with the baseline, participants demonstrated significant improvements. After receiving tPBM, patients showed enhanced cognitive efficiency, as evidenced by improved visual working memory performance, better learning in verbal memory tests, improved subjective sleep quality, fewer physical post-concussion symptoms, reduced pain intensity, and decreased PTSD symptoms. In contrast, no significant improvement was observed after patients received the sham tPBM. In addition, the statistically significant improvement in behavioral symptoms also reached the minimal clinically important difference, suggesting clinical significance. These findings support the potential of tPBM as a safe, non-invasive clinical intervention for cognitive deficits and associated symptoms in mTBI. Further exploration is encouraged to evaluate tPBM as a rehabilitation strategy for enhancing recovery in TBI patients.
9A comprehensive review on therapeutic potentials of photobiomodulation for neurodegenerative disorders.PubMed
Pooja Ramakrishnan, Aradhana Joshi, Mohamed Fazil, et al.
Life Sci. 2024 Jan 1;336:122334. doi: 10.1016/j.lfs.2023.122334. Epub 2023 Dec 5.
A series of experimental trials over the past two centuries has put forth Photobiomodulation (PBM) as a treatment modality that utilizes colored lights for various conditions. While in its cradle, PBM was used for treating simple conditions such as burns and wounds, advancements in recent years have extended the use of PBM for treating complex neurodegenerative diseases (NDDs). PBM has exhibited the potential to curb several symptoms and signs associated with NDDs. While several of the currently used therapeutics cause adverse side effects alongside being highly invasive, PBM on the contrary, seems to be broad-acting, less toxic, and non-invasive. Despite being projected as an ideal therapeutic for NDDs, PBM still isn't considered a mainstream treatment modality due to some of the challenges and knowledge gaps associated with it. Here, we review the advantages of PBM summarized above with an emphasis on the common mechanisms that underlie major NDDs and how PBM helps tackle them. We also discuss important questions such as whether PBM should be considered a mainstay treatment modality for these conditions and if PBM's properties can be harnessed to develop prophylactic therapies for high-risk individuals and also highlight important animal studies that underscore the importance of PBM and the challenges associated with it. Overall, this review is intended to bring the major advances made in the field to the spotlight alongside addressing the practicalities and caveats to develop PBM as a major therapeutic for NDDs.
10Photobiomodulation for traumatic brain injury and stroke.PubMed
Michael R Hamblin
J Neurosci Res. 2018 Apr;96(4):731-743. doi: 10.1002/jnr.24190. Epub 2017 Nov 13.
There is a notable lack of therapeutic alternatives for what is fast becoming a global epidemic of traumatic brain injury (TBI). Photobiomodulation (PBM) employs red or near-infrared (NIR) light (600-1100nm) to stimulate healing, protect tissue from dying, increase mitochondrial function, improve blood flow, and tissue oxygenation. PBM can also act to reduce swelling, increase antioxidants, decrease inflammation, protect against apoptosis, and modulate microglial activation state. All these mechanisms of action strongly suggest that PBM delivered to the head should be beneficial in cases of both acute and chronic TBI. Most reports have used NIR light either from lasers or from light-emitting diodes (LEDs). Many studies in small animal models of acute TBI have found positive effects on neurological function, learning and memory, and reduced inflammation and cell death in the brain. There is evidence that PBM can help the brain repair itself by stimulating neurogenesis, upregulating BDNF synthesis, and encouraging synaptogenesis. In healthy human volunteers (including students and healthy elderly women), PBM has been shown to increase regional cerebral blood flow, tissue oxygenation, and improve memory, mood, and cognitive function. Clinical studies have been conducted in patients suffering from the chronic effects of TBI. There have been reports showing improvement in executive function, working memory, and sleep. Functional magnetic resonance imaging has shown modulation of activation in intrinsic brain networks likely to be damaged in TBI (default mode network and salience network).
11Revisiting Transcranial Light Stimulation as a Stroke Therapeutic-Hurdles and Opportunities.PubMed
Wuwei Feng, Alexis Domeracki, Christine Park, et al.
Transl Stroke Res. 2023 Dec;14(6):854-862. doi: 10.1007/s12975-022-01103-7. Epub 2022 Nov 12.
Near-infrared laser therapy, a special form of transcranial light therapy, has been tested as an acute stroke therapy in three large clinical trials. While the NEST trials failed to show the efficacy of light therapy in human stroke patients, there are many lingering questions and lessons that can be learned. In this review, we summarize the putative mechanism of light stimulation in the setting of stroke, highlight barriers, and challenges during the translational process, and evaluate light stimulation parameters, dosages and safety issues, choice of outcomes, effect size, and patient selection criteria. In the end, we propose potential future opportunities with transcranial light stimulation as a cerebroprotective or restorative tool for future stroke treatment.
12Efficacy of Transcranial Photobiomodulation on Depressive Symptoms: A Meta-Analysis.PubMed
Yoonju Cho, Umit Tural, Dan V Iosifescu
Photobiomodul Photomed Laser Surg. 2023 Sep;41(9):460-466. doi: 10.1089/photob.2023.0041. Epub 2023 Aug 31.
Transcranial photobiomodulation (tPBM) is a novel, noninvasive, device-based intervention, which has been tested as a possible treatment for various neurological and psychiatric conditions. Recently, it has been investigated as an innovative treatment for major depressive disorder (MDD). There have been several animal and clinical studies that evaluated the underlying mechanism and the efficacy of its antidepressant effects, but results have been conflicting. Thus, we conducted the first meta-analysis on effects of tPBM on depressive symptoms. Thirty original articles on tPBM were retrieved, eight of them met criteria for inclusion to a random effects meta-analysis. tPBM appeared effective in decreasing depressive symptom severity regardless of diagnosis (Hedges' = 1.415, < 0.001, = 8), but a significant heterogeneity has been found. The meta-analysis of single-arm studies (baseline to endpoint changes) limited to participants with MDD has supported the significant effect of tPBM in reducing the depression severity, without a significant heterogeneity (Hedges' = 1.142, 95% confidence interval = 0.780-1.504, = 6.19, < 0.001, = 5). However, the meta-analysis of the few double-blind, sham-controlled studies in MDD has not supported the statistically significant superiority of tPBM over sham (Hedges' = 0.499, = 0.211, = 3), although a sample size bias is likely present. Overall, this meta-analysis provides weak support for the promising role of tPBM in the treatment of depressive symptoms. Dose finding studies to determine optimal tPBM parameters followed by larger, randomized, sham-controlled studies will be needed to fully demonstrate the antidepressant efficacy of tPBM.
13Photobiomodulation Therapy on Brain: Pioneering an Innovative Approach to Revolutionize Cognitive Dynamics.PubMed
Tahsin Nairuz, Sangwoo-Cho, Jong-Ha Lee
Cells. 2024 Jun 3;13(11):966. doi: 10.3390/cells13110966.
Photobiomodulation (PBM) therapy on the brain employs red to near-infrared (NIR) light to treat various neurological and psychological disorders. The mechanism involves the activation of cytochrome c oxidase in the mitochondrial respiratory chain, thereby enhancing ATP synthesis. Additionally, light absorption by ion channels triggers the release of calcium ions, instigating the activation of transcription factors and subsequent gene expression. This cascade of events not only augments neuronal metabolic capacity but also orchestrates anti-oxidant, anti-inflammatory, and anti-apoptotic responses, fostering neurogenesis and synaptogenesis. It shows promise for treating conditions like dementia, stroke, brain trauma, Parkinson's disease, and depression, even enhancing cognitive functions in healthy individuals and eliciting growing interest within the medical community. However, delivering sufficient light to the brain through transcranial approaches poses a significant challenge due to its limited penetration into tissue, prompting an exploration of alternative delivery methods such as intracranial and intranasal approaches. This comprehensive review aims to explore the mechanisms through which PBM exerts its effects on the brain and provide a summary of notable preclinical investigations and clinical trials conducted on various brain disorders, highlighting PBM's potential as a therapeutic modality capable of effectively impeding disease progression within the organism-a task often elusive with conventional pharmacological interventions.
14Mood Disorders in Youth: Complementary and Integrative Medicine.PubMed
Kirti Saxena, Sherin Kurian, Reena Kumar, et al.
Child Adolesc Psychiatr Clin N Am. 2023 Apr;32(2):367-394. doi: 10.1016/j.chc.2022.08.012.
Omega-3 polyunsaturated fatty acids, probiotics, vitamin C, vitamin D, folic acid and L-methyl folate, broad-spectrum micronutrients, N-acetylcysteine, physical activity, herbs, bright light therapy, melatonin, saffron, meditation, school-based interventions, and transcranial photobiomodulation are reviewed, with a focus on their use for treating mood disorders in children and adolescents. For each treatment, all published randomized controlled trials are summarized.
15Transcranial Photobiomodulation For The Management Of Depression: Current Perspectives.PubMed
Paula Askalsky, Dan V Iosifescu
Neuropsychiatr Dis Treat. 2019 Nov 22;15:3255-3272. doi: 10.2147/NDT.S188906. eCollection 2019.
Major depressive disorder (MDD) is a prevalent condition associated with high rates of disability, as well as suicidal ideation and behavior. Current treatments for MDD have significant limitations in efficacy and side effect burden. FDA-approved devices for MDD are burdensome (due to repeated in-office procedures) and are most suitable for severely ill subjects. There is a critical need for device-based treatments in MDD that are efficacious, well-tolerated, and easy to use. In this paper, we review a novel neuromodulation strategy, transcranial photobiomodulation (t-PBM) with near-infrared light (NIR). The scope of our review includes the known biological mechanisms of t-PBM, as well as its efficacy in animal models of depression and in patients with MDD. Theoretically, t-PBM penetrates into the cerebral cortex, stimulating the mitochondrial respiratory chain, and also significantly increases cerebral blood flow. Animal and human studies, using a variety of t-PBM settings and experimental models, suggest that t-PBM may have significant efficacy and good tolerability in MDD. In aggregate, these data support the need for large confirmatory studies for t-PBM as a novel, likely safe, and easy-to-administer antidepressant treatment.
16The Efficacy and Safety of Transcranial Photobiomodulation for Mild Cognitive Impairment Due to Alzheimer's Disease: A Randomized, Double-Blind, Sham-Controlled Study.PubMed
Hyelim Chun, Minha Lea Yoon, Hee Won Lee, et al.
Photobiomodul Photomed Laser Surg. 2025 Sep;43(9):411-416. doi: 10.1177/15578550251369575.
Transcranial photobiomodulation (tPBM) is a promising noninvasive neuromodulation modality with potential therapeutic benefits for neurodegenerative diseases. Infrared light delivered by a tPBM device penetrates the cortex, stimulating neuronal activity by increasing mitochondrial adenosine triphosphate production and enhancing regional cerebral blood flow. This study investigated the efficacy and safety of a self-administered, at-home, wearable tPBM device for improving cognitive function in individuals with mild cognitive impairment (MCI) due to Alzheimer's disease (AD). Individuals with MCI due to AD, diagnosed according to the National Institute on Aging and Alzheimer's Association criteria, with a Korean version of Mini-Mental State Examination-2 (K-MMSE2) score of 23-27 and a global Clinical Dementia Rating (CDR) score of 0.5-1.0 were enrolled. Subjects self-administered tPBM six times per week for 12 weeks. Assessments were conducted at weeks 7 and 13 using the Korean version of the Montreal Cognitive Assessment (K-MoCA), K-MMSE2, the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease, and the Geriatric Depression Scale. A total of 26 participants were enrolled. The treatment group showed a statistically significant improvement in K-MoCA scores at week 13 ( < 0.05) compared with the sham group. Although K-MMSE2 scores improved in the treatment group, the difference was not statistically significant. No serious adverse events were reported. Findings suggest that tPBM is an effective and safe home-use intervention for individuals with MCI, with promising therapeutic and preventative roles in Alzheimer's dementia.
17Transcranial low-level laser stimulation in the near-infrared-II region (1064 nm) for brain safety in healthy humans.PubMed
Zhilin Li, Yongheng Zhao, Yiqing Hu, et al.
Brain Stimul. 2024 Nov-Dec;17(6):1307-1316. doi: 10.1016/j.brs.2024.11.010. Epub 2024 Nov 30.
BACKGROUND: The use of near-infrared lasers for transcranial photobiomodulation (tPBM) offers a non-invasive method for influencing brain activity and is beneficial for various neurological conditions. However, comprehensive quantitative studies on its safety are lacking. OBJECTIVE: This study aims to investigate the safety of 1064-nm laser-based tPBM across brain structure, brain function, neural damage, cognitive ability and tolerance. METHODS: We employed a multimodal approach, using magnetic resonance imaging (MRI), electroencephalogram (EEG), biochemical analyses, and cognitive testing to quantitatively assess the potential adverse effects of tPBM on brain structure or function, neurons, glial cells, and executive function (EF). Additionally, a detailed questionnaire was used to evaluate subjective tolerance. RESULTS: At the whole-brain structural level, no significant variations in gray matter, white matter, or cerebrospinal fluid volume or density were observed as a result of tPBM. There was no increase in neuron-specific enolase (NSE) or S100β levels suggesting no neuronal damage, but an unexpected significant reduction in NSE was detected which requires further study to assess its implications. EEG, analyzed through power spectra and expert evaluation, revealed no potential disease-inducing effects. A series of cognitive tests demonstrated no impairment in any of the EF components. Furthermore, the questionnaire data revealed minimal discomfort across fatigue, itching, pain, burning, warmth, dizziness, and drowsiness. CONCLUSIONS: Our data indicate that 1064 nm laser tPBM does not induce adverse effects on brain structure or function, nor does it impair cognitive abilities. tPBM is safe for specific parameters, highlighting its good tolerability.
18Study of transcranial photobiomodulation at 945-nm wavelength: anxiety and depression.PubMed
Flávio Klinpovous Kerppers, Kesia Maria Mangoni Gonçalves Dos Santos, Maria Elvira Ribeiro Cordeiro, et al.
Lasers Med Sci. 2020 Dec;35(9):1945-1954. doi: 10.1007/s10103-020-02983-7. Epub 2020 Mar 7.
Transcranial photobiomodulation is an innovative method for the stimulation of neural activity which consists of the exposure of neural tissue to low-level light irradiance. In the present study, light-emitting diodes (LEDs) were used as light source due to their practicality and low cost. The objective was to analyze the effects of transcranial photobiomodulation using 945-nm LED in university students with anxiety and depression. Sample was composed of 22 individuals (17-25 years of age) divided into 2 groups of 11. LED group was treated with 945-nm LEDs for 1 min and 25 s (9.35 J/cm), while in the placebo group, the device was off when placed in contact with the frontal bone for the same amount of time as in treatment group. Participants were evaluated at baseline and after 30 days with the hospital anxiety and depression scale (HADS), the faces test, the designs test, and the grip strength test. On the HADS for anxiety, the mean PAB, PAA, PhAB, and PhAA were 13.89 ± 3.55, 12.82 ± 3.18, 10.75 ± 2.49, and 6.66 ± 2.50 points, respectively. In the HADS for depression, the mean for the PDB group was 13.89 ± 3.55 points, in the PhDB group 12.82 ± 3.18 points, in the PDA group 10.75 ± 2.49 points, and in the PhDA group 6.66 ± 2.50 points. In the PA and PD groups, mean values of 8.0 ± 1.5 and 8.9 ± 1.26 scores were obtained, but did not reach significance; however, between PA and PhD analysis, a significance level of p = 0.0003 was obtained. The 945-nm LED transcranial photobiomodulation improves brain activity and may clinically decrease anxiety and depression.
19Advances in photobiomodulation for cognitive improvement by near-infrared derived multiple strategies.PubMed
Wei-Tong Pan, Pan-Miao Liu, Daqing Ma, et al.
J Transl Med. 2023 Feb 22;21(1):135. doi: 10.1186/s12967-023-03988-w.
Cognitive function is an important ability of the brain, but cognitive dysfunction can easily develop once the brain is injured in various neuropathological conditions or diseases. Photobiomodulation therapy is a type of noninvasive physical therapy that is gradually emerging in the field of neuroscience. Transcranial photobiomodulation has been commonly used to regulate neural activity in the superficial cortex. To stimulate deeper brain activity, advanced photobiomodulation techniques in conjunction with photosensitive nanoparticles have been developed. This review addresses the mechanisms of photobiomodulation on neurons and neural networks and discusses the advantages, disadvantages and potential applications of photobiomodulation alone or in combination with photosensitive nanoparticles. Photobiomodulation and its associated strategies may provide new breakthrough treatments for cognitive improvement.
20Very Low-Level Transcranial Photobiomodulation for Major Depressive Disorder: The ELATED-3 Multicenter, Randomized, Sham-Controlled Trial.PubMed
Dan V Iosifescu, Richard J Norton, Umit Tural, et al.
J Clin Psychiatry. 2022 Aug 8;83(5):21m14226. doi: 10.4088/JCP.21m14226.
Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light might represent a treatment for major depressive disorder (MDD). However, the dosimetry of administered t-PBM varies widely. We tested the efficacy of t-PBM with low irradiance, low energy per session, and low number of sessions in individuals with MDD. A 2-site, double-blind, sham-controlled study was conducted of adjunct t-PBM NIR (830 nm; continuous wave; 35.8 cm treatment area; 54.8 mW/cm irradiance; 65.8 J/cm fluence, 20 min/session; ~2 W total power; 2.3 kJ total energy per session), delivered to the prefrontal cortex, bilaterally, twice a week for 6 weeks, in subjects diagnosed with MDD per the criteria. Subjects were recruited between August 2016 and May 2018. A sequential parallel comparison design was used: 18 nonresponders to sham in phase 1 (6 weeks) were re-randomized in phase 2. The primary outcome was reduction in depression severity (Hamilton Depression Rating Scale [HDRS-17] and Quick Inventory of Depressive Symptomatology-Clinician Rating [QIDS-C] scores) from baseline. Statistical analyses used R package SPCDAnalyze2, including all subjects with ≥ 1 post-randomization evaluation. Of the 54 subjects recruited, we included 49 MDD subjects in the analysis (71% female, mean ± SD age 40.8 ± 16.1 years). There were no significant differences between t-PBM and sham with respect to the change in HDRS-17 ( = -0.319, = .751) or QIDS-C ( = -0.499, = .620) scores. The sham effect was reasonably low. Mostly uncontrolled studies suggest the efficacy of t-PBM for MDD; however, its optimal dose is still to be defined. A minimal dose threshold is likely necessary, similarly to other neuromodulation techniques in MDD (electroconvulsive therapy, transcranial magnetic stimulation). We established a threshold of inefficacy of t-PBM for MDD, based on combined low irradiance, low energy per session, and low number of sessions. ClinicalTrials.gov identifier: NCT02959307.