Inflammation in obsessive-compulsive disorder: A literature review and hypothesis-based potential of transcranial photobiomodulation.

Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric disorder that affects about 2%-3% of the global population. Despite the availability of several treatments, many patients with OCD do not respond adequately, highlighting the need for new therapeutic approaches. Recent studies have associated various inflammatory processes with the pathogenesis of OCD, including alterations in peripheral immune cells, alterations in cytokine levels, and neuroinflammation. These findings suggest that inflammation could be a promising target for intervention. Transcranial photobiomodulation (t-PBM) with near-infrared light is a noninvasive neuromodulation technique that has shown potential for several neuropsychiatric disorders. However, its efficacy in OCD remains to be fully explored. This study aimed to review the literature on inflammation in OCD, detailing associations with T-cell populations, monocytes, NLRP3 inflammasome components, microglial activation, and elevated proinflammatory cytokines such as TNF-α, CRP, IL-1ß, and IL-6. We also examined the hypothesis-based potential of t-PBM in targeting these inflammatory pathways of OCD, focusing on mechanisms such as modulation of oxidative stress, regulation of immune cell function, reduction of proinflammatory cytokine levels, deactivation of neurotoxic microglia, and upregulation of BDNF gene expression. Our review suggests that t-PBM could be a promising, noninvasive intervention for OCD, with the potential to modulate underlying inflammatory processes. Future research should focus on randomized clinical trials to assess t-PBM's efficacy and optimal treatment parameters in OCD. Biomarker analyses and neuroimaging studies will be important in understanding the relationship between inflammatory modulation and OCD symptom improvement following t-PBM sessions.

Transcranial photobiomodulation for neurodevelopmental disorders: a narrative review.

BACKGROUND: Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Down syndrome (DS) significantly impact social, communicative, and behavioral functioning. Transcranial photobiomodulation (t-PBM) with near-infrared light is a promising non-invasive neurostimulation technique for neuropsychiatric disorders, including NDDs. This narrative review aimed to examine the preclinical and clinical evidence of photobiomodulation (PBM) in treating NDDs. METHODS: A comprehensive search across six databases was conducted, using a combination of MeSH terms and title/abstract keywords: "photobiomodulation", "PBM", "neurodevelopmental disorders", "NDD", and others. Studies applying PBM to diagnosed NDD cases or animal models replicating NDDs were included. Protocols, reviews, studies published in languages other than English, and studies not evaluating clinical or cognitive outcomes were excluded. RESULTS: Nine studies were identified, including one preclinical and eight clinical studies (five on ASD, two on ADHD, and one on DS). The reviewed studies encompassed various t-PBM parameters (wavelengths: 635-905 nm) and targeted primarily frontal cortex areas. t-PBM showed efficacy in improving disruptive behavior, social communication, cognitive rigidity, sleep quality, and attention in ASD; in enhancing attention in ADHD; and in improving motor skills and verbal fluency in DS. Minimal adverse effects were reported. Proposed mechanisms involve enhanced mitochondrial function, modulated oxidative stress, and reduced neuroinflammation. CONCLUSIONS: t-PBM emerges as a promising intervention for NDDs, with potential therapeutic effects across ASD, ADHD, and DS. These findings underscore the need for further research, including larger-scale, randomized sham-controlled clinical trials with comprehensive biomarker analyses, to optimize treatment parameters and understand the underlying mechanisms associated with the effects of t-PBM.

Efficacy of transcranial photobiomodulation in the treatment for major depressive disorder: A TMS-EEG and pilot study.

BACKGROUND: Major depressive disorder (MDD) was a prevalent mental condition that may be accompanied by decreased excitability of left frontal pole (FP) and abnormal brain connections. An 820 nm tPBM can induce an increase in stimulated cortical excitability. The purpose of our study was to establish how clinical symptoms and time-varying brain network connectivity of MDD were affected by transcranial photobiomodulation (tPBM). METHODS: A total of 11 patients with MDD received 820 nm tPBM targeting the left FP for 14 consecutive days. The severity of symptoms was evaluated by neuropsychological assessments at baseline, after treatment, 4-week and 8-week follow-up; 8-min transcranial magnetic stimulation combined electroencephalography (TMS-EEG) was performed for five healthy controls and five patients with MDD before and after treatment, and time-varying EEG network was analyzed using the adaptive-directed transfer function. RESULTS: All of scales scores in the 11 patients decreased significantly after 14-day tPBM (p < .01) and remained at 8-week follow-up. The time-varying brain network analysis suggested that the brain regions with enhanced connection information outflow in MDD became gradually more similar to healthy controls after treatment. CONCLUSIONS: This study showed that tPBM of the left FP could improve symptoms of patients with MDD and normalize the abnormal network connections.

Pulsed transcranial photobiomodulation generates distinct beneficial neurocognitive effects compared with continuous wave transcranial light.

Previous research has demonstrated the beneficial effect brought by transcranial photobiomodulation (tPBM). The present study is a further investigation of pulsed transcranial light delivery, from the perspective of wavelength, operation mode, and pulse frequency. A total of 56 healthy young adults (28 males and 28 females) were included in this randomized, sham-controlled experimental study. The wavelength of tPBM was 660 nm and 850 nm, and under each wavelength, subjects were randomly assigned to one of the following four treatments: (1) sham control; (2) continuous-wave (CW) tPBM; (3) pulsed-wave (PW) tPBM (40 Hz); and (4) PW tPBM (100 Hz). The tPBM duration was 8 min and the mean power density was fixed at 250 mW/cm2. Karolinska Sleepiness Scale (KSS) questionnaire, psychomotor vigilance task (PVT), and delayed match-to-sample (DMS) task were completed by subjects before and after the intervention to test whether PW tPBM produced distinct beneficial effects with measures of sleepiness, attention, and memory. 32-channel electroencephalography (EEG) signals were obtained from subjects before, during and after receiving tPBM or sham intervention. Paired sample T test showed that the KSS score, the number of correct responses of PVT, and DMS rate correct score (RCS) of PW tPBM groups improved significantly after intervention (p < 0.05). With regard to EEG analysis, paired one-way repeated ANOVA test showed that during the intervention of PW tPBM, the average power within the Gamma band was higher than the baseline (p < 0.05). Our study presented that PW tPBM could generate better beneficial cognitive effects and change brain electrical activity under certain circumstances.

Transcranial photobiomodulation therapy associated with cardiorespiratory rehabilitation in spastic subjects.

The objective of this study was to evaluate the effects of cardiorespiratory rehabilitation (CR) and transcranial photobiomodulation (tPBM) on exercise tolerance (ET), heart rate variability (HRV), and peripheral muscle activity in individuals with spasticity. Fifteen participants with spasticity were randomly assigned to two groups: the tPBM group (tPBMG) consisted of eight volunteers who underwent tPBM (on mode) and CR, while the control group (CG) consisted of seven volunteers who underwent simulated tPBM (off mode) and CR. The CR program included 12 weeks of treatment, twice a week for one hour, involving aerobic exercises and lower limb strengthening. For tPBM, a cluster with three lasers (λ = 680 nm, 808 nm), with a power of 100 mW/laser and energy of 36 J, applied to the F7, F8, and Fpz points. The following parameters were evaluated after 8 and 12 weeks: ET, HRV, and surface electromyography (EMG) of the rectus femoris muscle during orthostasis (ORT), isometric squatting (ISOM), and isotonic squatting (ISOT). Both groups showed a 40% increase in ET for the CG and a 30% increase for the tPBMG. The CG had more pronounced parasympathetic modulation alterations during post-exercise effort and recovery compared to the tPBMG. The EMG results showed that the tPBMG exhibited progressive improvement in muscle activity during ISOM and ISOT, as well as a decrease in the interlimb difference. In conclusion, both CR and tPBMG demonstrated improvements in ET. However, tPBMG specifically showed promising effects on HRV modulation and peripheral muscle electrical activity, providing additional benefits compared to CR alone.

Effect of transcranial near-infrared photobiomodulation on cognitive outcomes in D-galactose/AlCl3 induced brain aging in BALB/c mice.

Brain photobiomodulation (PBM) therapy (PBMT) modulates various biological and cognitive processes in senescence rodent models. This study was designed to investigate the effects of transcranial near-infrared (NIR) laser treatment on D-galactose (D-gal)/aluminum chloride (AlCl3) induced inflammation, synaptic dysfunction, and cognitive impairment in mice. The aged mouse model was induced by subcutaneously injecting D-gal (60 mg/kg/day) followed by intragastrically administering AlCl3 (200 mg/kg/day) for 2 months. NIR PBM (810 nm laser, 32, 16, and 8 J/cm2) was administered transcranially every other day (3 days/week) for 2 months. Social, contextual, and spatial memories were assessed by social interaction test, passive avoidance test, and Lashley III maze, respectively. Then, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and synaptic markers including growth-associated protein 43 (GAP-43), post-synaptic density-95 (PSD-95), and synaptophysin (SYN) levels were measured in the hippocampus using western blot method. Behavioral results revealed that NIR PBM at fluencies of 16 and 8 J/cm2 could reduce D-gal/AlCl3 impaired social and spatial memories. Treatment with NIR attenuated neuroinflammation through down-regulation of TNF-α and IL-6. Additionally, NIR significantly inhibited the down-regulation of GAP-43 and SYN. The results indicate that transcranial PBM at the fluencies 16 and 8 J/cm2 effectively prevents cognitive impairment in mice model of aging by inhibiting the production of the inflammatory cytokines and enhancing synaptic markers.

Synergistic effects of combined therapy with transcranial photobiomodulation and enriched environment on depressive- and anxiety-like behaviors in a mice model of noise stress.

The development of anxiety and depression due to chronic exposure to noise stress has remained as an unsolved health problem so far. Despite the studies suggesting the neuroenhancement effects of transcranial photobiomodulation (tPBM) and housing in an enriched environment (EE), the combined effects of these treatments have not been elucidated yet. Also, there is no available data on the relationship between the application of tPBM and hippocampal brain-derived neurotrophic factor (BDNF) expression in animal models of stress. The present study aims to investigate the application of the tPBM and EE (alone or in combination) on depressive- and anxiety-like behaviors in a mice model of noise stress. Mice were divided into five groups: control, noise, noise + EE, noise + tPBM, and noise + EE + tPBM. Except for the control group, other groups were subjected to 110 dB SPL white noise for 4 h/day for 14 consecutive days and received their respective treatments. Forced Swimming Test (FST) was used to evaluate depressive-like behaviors. Elevated Plus Maze (EPM) and Open Field Test (OFT) were used to evaluate anxiety-like behaviors. BDNF, tyrosine receptor kinase B (TrkB), and cAMP response element-binding (CREB) protein levels in the hippocampus were determined by the Western blot method, and also serum corticosterone levels were assessed using an ELISA kit. Exposure to noise stress significantly elevated serum corticosterone level; downregulated hippocampal BDNF, TrkB, and CREB protein expressions; and resulted in depressive- and anxiety-like behaviors. While, the application of tPBM (810 nm wavelength, 8 J/cm2 fluence, 10 Hz pulsed wave mode), housing in EE, and their combination lowered corticosterone levels, upregulated the BDNF/TrkB/CREB signaling pathway in the hippocampus, and improved behavioral outcomes in noise stress subjected mice. Our finding revealed the improving effects of tPBM and EE on depressive and anxiety-like behaviors induced by noise stress, possibly by augmenting the BDNF/TrkB/CREB signaling pathway.

The effect of transcranial photobiomodulation on cognitive function and attentional performance of older women with mild cognitive impairment: a randomized controlled trial.

Introduction: Mild cognitive impairment (MCI) is a progressive age-related condition caused by physiological and structural changes in the brain, such as neurodegeneration and hypometabolism. Transcranial photobiomodulation (tPBM) is a neuromodulation technique that improves brain metabolism and oxygenation by irradiating red to near-infrared light on a specific area of the head. This study aimed to investigate the effect of multi-session tPBM on the cognitive capacities and attentional function of older women with MCI. Material and methods: In this randomized controlled trial, 42 older women with MCI were randomly assigned to 2 equal groups: real and sham. The mini-mental state examination (MMSE) and the attentional Go/No-Go task were used to examine the patients. On the right frontal-pole of the cortex, 5 sessions of 850 nm tPBM were given. Re-examinations were conducted on the participants. For the Go/No-Go task, the reaction time to the target (RTT), the percentage of correct trials (PCT), and the efficiency score (ES) were measured. Results: The findings revealed a significant interaction between group × time for MMSE (F (1, 40) = 20, p < 0.001, h2 = 0.33), and the post-hoc paired-samples t-tests revealed a substantial rise in the mean MMSE in the real group (t = 15.9; p = 0.001; d = 9.3). Additionally, for ES (F (1, 40) = 19, p < 0.001, h2 = 0.32), RTT (F (1, 40) = 17, p < 0.001, h2 = 0.38), and PCT (F (1, 40) = 13, p < 0.001, h2 = 0.31), a significant group × time interaction was discovered, and post-hoc paired-samples t-tests revealed a significant improvement in attention performance of the real group for increases in the mean of ES (F (1,40) = 20, p < 0.001, h2 = 0.33), (t = 5.3, p < 0.001, d = 0.034), decreases in the mean of RTT (t = 4.8; p = 0.001; d = -37.4), and increases in the mean of PCT (t = 2.67; p = 0.015; d = 6.3). Conclusions: According to the findings of this study, tPBM had a positive effect on older people's attention and cognitive abilities.

Transcranial Photobiomodulation of Clearance of Beta-Amyloid from the Mouse Brain: Effects on the Meningeal Lymphatic Drainage and Blood Oxygen Saturation of the Brain.

Here, we demonstrate the therapeutic effects of transcranial photobiomodulation (tPBM, 1267 nm, 32 J/cm2, a 9-day course) in mice with the injected model of Alzheimer's disease (AD) associated with accumulation of beta-amyloid (Aß) in the brain resulting in neurocognitive deficit vs. the control group (CG) (the neurological severity score (NNS), AD 3.67 ± 0.58 vs. CG 1.00 ± 0.26%, p < 0.05) and mild cerebral hypoxia (AD 72 ± 6% vs. CG 97 ± 2%, p < 0.001). The course of tPBM improved neurocognitive status of mice with AD (NNS, AD 2.03 ± 0.14 vs. CG 1.00 ± 0.26, vs. 2.03 ± 0.14, p < 0.05) due to stimulation of clearance of Aß from the brain via the meningeal lymphatic vessels (the immunohistochemical and confocal data) and an increase in blood oxygen saturation of the brain tissues (the pulse oximetry data) till 85 ± 2%, p < 0.05. These results open breakthrough strategies for non-pharmacological therapy of AD and clearly demonstrate that tPBM might be a promising therapeutic target for preventing or delaying AD based on stimulation of oxygenation of the brain tissues and activation of clearance of toxic molecules via the cerebral lymphatics.

[Transcranial photobiomodulation in therapy of neurodegenerative diseases of the brain: theoretical background and clinical effectiveness]. / Transkranial'naya fotobiomodulyatsiya v terapii neirodegenerativnykh zabolevanii golovnogo mozga: teoreticheskie predposylki i klinicheskaya effektivnost'.

Transcranial photobiomodulation (tPBM) is a form of light therapy that uses monochromatic visible and infrared light from non-ionizing radiation sources (lasers, LEDs) placed on the scalp, forehead, or intranasally to project light directly to target areas of the brain. Accumulated experimental and clinical data indicate the safety and potential efficacy of tPBM in some central nervous system diseases.This article briefly reviews the general concepts of tPBM, the results of experimental and clinical studies on the efficacy of tPBM in Alzheimer's disease, Parkinson's disease, and brain stroke. The possible mechanisms of the tPBM therapeutic effect and the need to choose optimal exposure parameters are discussed. Although the evidence base regarding the efficacy of tPBM in neurodegenerative and vascular brain diseases is still insufficient, analysis of the published data justifies considering tPBM as a promising method of adjuvant therapy for some central nervous system diseases.

Transcranial Photobiomodulation (tPBM) With 1,064-nm Laser to Improve Cerebral Metabolism of the Human Brain In Vivo.

BACKGROUND AND OBJECTIVES: In our previous proof-of-principle study, transcranial photobiomodulation (tPBM) with 1,064-nm laser was reported to significantly increase concentration changes of oxygenated hemoglobin (∆[HbO]) and oxidized-state cytochrome c oxidase (∆[oxi-CCO]) in the human brain. This paper further investigated (i) its validity in two different subsets of young human subjects at two study sites over a period of 3 years and (ii) age-related effects of tPBM by comparing sham-controlled increases of ∆[HbO] and ∆[oxi-CCO] between young and older adults. STUDY DESIGN/MATERIALS AND METHODS: We measured sham-controlled ∆[HbO] and ∆[oxi-CCO] using broadband near-infrared spectroscopy (bb-NIRS) in 15 young (26.7 ± 2.7 years of age) and 5 older (68.2 ± 4.8 years of age) healthy normal subjects before, during, and after right-forehead tPBM/sham stimulation with 1,064-nm laser. Student t tests were used to test statistical differences in tPBM-induced ∆[HbO] and ∆[oxi-CCO] (i) between the 15 young subjects and those of 11 reported previously and (ii) between the two age groups measured in this study. RESULTS: Statistical analysis showed that no significant difference existed in ∆[HbO] and ∆[oxi-CCO] during and post tPBM between the two subsets of young subjects at two study sites over a period of 3 years. Furthermore, the two age groups showed statistically identical net increases in sham-controlled ∆[HbO] and ∆[oxi-CCO]. CONCLUSIONS: This study provided strong evidence to validate/confirm our previous findings that tPBM with 1,064-nm laser enables to increase cerebral ∆[HbO] and ∆[oxi-CCO] in the human brain, as measured by bb-NIRS. Overall, it demonstrated the robust reproducibility of tPBM being able to improve cerebral hemodynamics and metabolism of the human brain in vivo in both young and older adults. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals, Inc.

Transcranial photobiomodulation prevents anxiety and depression via changing serotonin and nitric oxide levels in brain of depression model mice: A study of three different doses of 810 nm laser.

OBJECTIVES: The effectiveness of transcranial photobiomodulation (TPBM) in treating anxiety and depression disorders is a demonstrated and identified issue. However, the optimum therapeutic dose and the underlying mechanism of action are not fully understood. In this study, the therapeutic effects of three different near-infrared (NIR) doses on anxiety- and depression-like behaviors as well as cerebral levels of serotonin (5-HT) and nitric oxide (NO) were evaluated in a mouse model of chronic restraint stress (CRS). MATERIALS AND METHODS: CRS procedure (3 hours/day, over 3 weeks) was performed as a typical stress model to study anxiety and depression along with laser treatment (3 times/week, over 3 weeks), which began simultaneously with CRS. A NIR diode laser (810 nm wavelength, 10 Hz) with the output power of 200 mW and power density of 4.75 W/cm2 was implemented to deliver three different doses of 4, 8, and 16 J/cm2 to the cerebral cortex of mice. Behavioral experiments including open field, tail suspension, and elevated plus maze tests as well as serum cortisol levels were assessed to evaluate the anti-anxiety and anti-depressive effects of NIR TPBM. The changes of 5-HT and NO levels in the prefrontal cortex (PFC) and hippocampus (Hipp) were assessed. RESULTS: CRS procedure induced anxiety- and depression-like behaviors, increased serum cortisol levels, decreased 5-HT and increased NO levels in the PFC and Hipp areas. NIR TPBM improved behavioral results, decreased serum cortisol levels, increased 5-HT and decreased NO concentrations in the PFC and Hipp. A dose of 8 J/cm2 of NIR TPBM showed the maximum effects on behavioral and molecular results, while a decline was observed from the optimum effects at both lower (4 J/cm2 ) and higher (16 J/cm2 ) doses. CONCLUSION: Our results demonstrated that NIR TPBM had an anti-anxiety and anti-depressive effect in CRS mice, which is probably linked to increasing 5-HT and decreasing NO levels in the PFC and Hipp areas. Also, the maximum anti-anxiety and anti-depressive effect was produced at dose of 8 J/cm2 . Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Transcranial Photobiomodulation Therapy as an Intervention for Opioid Cravings and Depression: A Pilot Cohort Study.

Introduction: The opioid crisis, a declared national health emergency, has prompted the exploration of innovative treatments to address the pervasive issues of opioid cravings and associated depression. Aims: This pilot cohort study investigated the efficacy of transcranial Photobiomodulation (tPBM) therapy using the SunPowerLED helmet to alleviate these symptoms in individuals undergoing treatment for opioid addiction at a rehabilitation center in West Virginia. Methods: Employing a quasi-experimental design, this study enrolled participants into two groups: one receiving tPBM therapy alongside standard care and a control group receiving standard care alone. The helmet features include the following: total wavelength = 810 nm, total irradiance = 0.06 W/cm2 (60 m W/cm2), and total fluence = 172.8J/cm2. Results: The results of the Wilcoxon signed-rank tests for within-group analysis and Mann-Whitney U tests for between-group comparisons revealed statistically significant reductions in the intensity (W = 7.36, p = 0.012), time (W = 6.50, p = 0.015), frequency (W = 6.50, p = 0.010), and total scores of opioid cravings (W = 7.50, p = 0.009), as well as improvements in depression symptoms (W= 8.00, p = 0.005) within the PBM group compared to the non-PBM group. Discussion: These findings suggest that transcranial PBM therapy could be a promising noninvasive intervention for reducing opioid cravings and depressive symptoms in individuals with opioid use disorder, warranting further investigation through larger randomized controlled trials.

Can transcranial photobiomodulation improve cognitive function in TBI patients? A systematic review.

Introduction: Transcranial photobiomodulation (tPBM) is a non-invasive neuromodulation technology which has become a promising therapy for treating many brain diseases. Although it has been confirmed in studies targeting neurological diseases including Alzheimer's and Parkinson's that tPBM can improve cognitive function, the effectiveness of interventions targeting TBI patients remains to be determined. This systematic review examines the cognitive outcomes of clinical trials concerning tPBM in the treatment of traumatic brain injury (TBI). Methods: We conducted a systematic literature review, following the PRISMA guidelines. The PubMed, Web of Science, Scopus, EMBASE, and Cochrane Library databases were searched before October 31, 2023. Results: The initial search retrieved 131 articles, and a total of 6 studies were finally included for full text-analysis after applying inclusion and exclusion criteria. Conclusion: Results showed improvements in cognition for patients with chronic TBI after tPBM intervention. The mechanism may be that tPBM increases the volume of total cortical gray matter (GM), subcortical GM, and thalamic, improves cerebral blood flow (CBF), functional connectivity (FC), and cerebral oxygenation, improving brain function. However, due to the significant heterogeneity in application, we cannot summarize the optimal parameters for tPBM treatment of TBI. In addition, there is currently a lack of RCT studies in this field. Therefore, given this encouraging but uncertain finding, it is necessary to conduct randomized controlled clinical trials to further determine the role of tPBM in cognitive rehabilitation of TBI patients.

Simultaneous MEG and EEG source imaging of electrophysiological activity in response to acute transcranial photobiomodulation.

Introduction: Transcranial photobiomodulation (tPBM) is a non-invasive neuromodulation technique that improves human cognition. The effects of tPBM of the right forehead on neurophysiological activity have been previously investigated using EEG in sensor space. However, the spatial resolution of these studies is limited. Magnetoencephalography (MEG) is known to facilitate a higher spatial resolution of brain source images. This study aimed to image post-tPBM effects in brain space based on both MEG and EEG measurements across the entire human brain. Methods: MEG and EEG scans were concurrently acquired for 6 min before and after 8-min of tPBM delivered using a 1,064-nm laser on the right forehead of 25 healthy participants. Group-level changes in both the MEG and EEG power spectral density with respect to the baseline (pre-tPBM) were quantified and averaged within each frequency band in the sensor space. Constrained modeling was used to generate MEG and EEG source images of post-tPBM, followed by cluster-based permutation analysis for family wise error correction (p < 0.05). Results: The 8-min tPBM enabled significant increases in alpha (8-12 Hz) and beta (13-30 Hz) powers across multiple cortical regions, as confirmed by MEG and EEG source images. Moreover, tPBM-enhanced oscillations in the beta band were located not only near the stimulation site but also in remote cerebral regions, including the frontal, parietal, and occipital regions, particularly on the ipsilateral side. Discussion: MEG and EEG results shown in this study demonstrated that tPBM modulates neurophysiological activity locally and in distant cortical areas. The EEG topographies reported in this study were consistent with previous observations. This study is the first to present MEG and EEG evidence of the electrophysiological effects of tPBM in the brain space, supporting the potential utility of tPBM in treating neurological diseases through the modulation of brain oscillations.

Transcranial photobiomodulation for brain diseases: review of animal and human studies including mechanisms and emerging trends.

The brain diseases account for 30% of all known diseases. Pharmacological treatment is hampered by the blood-brain barrier, limiting drug delivery to the central nervous system (CNS). Transcranial photobiomodulation (tPBM) is a promising technology for treating brain diseases, due to its effectiveness, non-invasiveness, and affordability. tPBM has been widely used in pre-clinical experiments and clinical trials for treating brain diseases, such as stroke and Alzheimer's disease. This review provides a comprehensive overview of tPBM. We summarize emerging trends and new discoveries in tPBM based on over one hundred references published in the past 20 years. We discuss the advantages and disadvantages of tPBM and highlight successful experimental and clinical protocols for treating various brain diseases. A better understanding of tPBM mechanisms, the development of guidelines for clinical practice, and the study of dose-dependent and personal effects hold great promise for progress in treating brain diseases.

Directed physiological networks in the human prefrontal cortex at rest and post transcranial photobiomodulation.

Cerebral infra-slow oscillation (ISO) is a source of vasomotion in endogenic (E; 0.005-0.02 Hz), neurogenic (N; 0.02-0.04 Hz), and myogenic (M; 0.04-0.2 Hz) frequency bands. In this study, we quantified changes in prefrontal concentrations of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics, and electroencephalogram (EEG) powers as electrophysiological activity, using concurrent measurements of 2-channel broadband near-infrared spectroscopy and EEG on the forehead of 22 healthy participants at rest. After preprocessing, the multi-modality signals were analyzed using generalized partial directed coherence to construct unilateral neurophysiological networks among the three neurophysiological metrics (with simplified symbols of HbO, CCO, and EEG) in each E/N/M frequency band. The links in these networks represent neurovascular, neurometabolic, and metabolicvascular coupling (NVC, NMC, and MVC). The results illustrate that the demand for oxygen by neuronal activity and metabolism (EEG and CCO) drives the hemodynamic supply (HbO) in all E/N/M bands in the resting prefrontal cortex. Furthermore, to investigate the effect of transcranial photobiomodulation (tPBM), we performed a sham-controlled study by delivering an 800-nm laser beam to the left and right prefrontal cortex of the same participants. After performing the same data processing and statistical analysis, we obtained novel and important findings: tPBM delivered on either side of the prefrontal cortex triggered the alteration or reversal of directed network couplings among the three neurophysiological entities (i.e., HbO, CCO, and EEG frequency-specific powers) in the physiological network in the E and N bands, demonstrating that during the post-tPBM period, both metabolism and hemodynamic supply drive electrophysiological activity in directed network coupling of the prefrontal cortex (PFC). Overall, this study revealed that tPBM facilitates significant modulation of the directionality of neurophysiological networks in electrophysiological, metabolic, and hemodynamic activities.

Transcranial photobiomodulation on the left inferior frontal gyrus enhances Mandarin Chinese L1 and L2 complex sentence processing performances.

This study investigated the causal enhancing effect of transcranial photobiomodulation (tPBM) over the left inferior frontal gyrus (LIFG) on syntactically complex Mandarin Chinese first language (L1) and second language (L2) sentence processing performances. Two (L1 and L2) groups of participants (thirty per group) were recruited to receive the double-blind, sham-controlled tPBM intervention via LIFG, followed by the sentence processing, the verbal working memory (WM), and the visual WM tasks. Results revealed a consistent pattern for both groups: (a) tPBM enhanced sentence processing performance but not verbal WM for linear processing of unstructured sequences and visual WM performances; (b) Participants with lower sentence processing performances under sham tPBM benefited more from active tPBM. Taken together, the current study substantiated that tPBM enhanced L1 and L2 sentence processing, and would serve as a promising and cost-effective noninvasive brain stimulation (NIBS) tool for future applications on upregulating the human language faculty.

Preventive effects of transcranial photobiomodulation on epileptogenesis in a kainic acid-induced rat epilepsy model.

OBJECTIVE: Temporal lobe epilepsy affects nearly 50 million people worldwide and is a major burden to families and society. A significant portion of patients are living in developing countries with limited access to therapeutic resources. This highlights the urgent need to develop more readily available, noninvasive treatments for seizure control. This research explored the effectiveness of transcranial photobiomodulation (tPBM), a non-invasive method utilizing photon-tissue interactions, for preventing epileptogenesis and controlling seizures. METHODS: In a kainic acid (KA)-induced rat model of epilepsy, two different wavelengths of tPBM, 808 nm and 940 nm, were applied separately in two groups of animals (KA+808 and KA+940). The ability of tPBM for seizure control was evaluated by comparing the occurrence rate of interictal epileptiform discharges (IED) and behavioral seizures among three groups: KA, KA+808, KA+940. Prevention of epileptogenesis was assessed by comparing the occurrence rate of high frequency oscillations (HFOs), especially fast ripple (FR) rate, among the three groups. Nissl staining and immunostaining for the apoptosis marker caspase-3 were used as indications of neuroprotection. RESULTS: The KA+808 group and the KA+940 group showed significantly lower FR and IED rates compared to the KA group. Weekly FR rates started to drop during the first week of tPBM treatment. The KA+808 and KA+940 groups also displayed milder seizure behaviors and less neuronal loss in hippocampal areas compared to KA rats without tPBM treatment. Similarly, lower caspase-3 levels in the KA+808 and KA+940 compared with the KA group suggested effectiveness of tPBM in reducing cell death. SIGNIFICANCE: tPBM of 808 nm/940 nm showed effectiveness in suppressing epileptogenesis and ictogenesis in the KA-induced rat epilepsy model. This effectiveness of tPBM can be linked to the neuroprotection benefits of photon-tissue interactions. Further studies are warranted to elucidate the fundamental mechanism of tPBM protection, determine optimal treatment parameters and validate its effectiveness in other epilepsy models.

Effect of transcranial photobiomodulation on electrophysiological activity of brain in healthy individuals: A scoping review.

BACKGROUND OBJECTIVE: Transcranial photobiomodulation (tPBM) is a safe and non-invasive treatment that has recently emerged as an effective technique to apply near-infrared or red light to activate neural tissues. The objective is to review the literature on the effect of tPBM on electrophysiological activity in healthy individuals. METHODS: Literature was searched through PubMed, Scopus, Web of Science, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Embase, and Ovid for transcranial photobiomodulation therapy in healthy individuals age group 18-80 years of either gender having electroencephalography as an outcome. Critical appraisal of included Randomized Controlled Trials and non-randomized experimental studies was done using Joanna Briggs Institute (JBI) critical appraisal tool. RESULTS: A database search yielded a total of 4156 results. After eliminating 2626 duplicates, 1530 records were left. 32 articles were considered for full-text screening after 1498 records were excluded through title and abstract screening. 10 articles were included in this review. tPBM has been found to increase the higher electrophysiological oscillations and there is inconclusive evidence targeting the lower oscillatory electrophysiological frequencies. CONCLUSION: Transcranial photobiomodulation can have promising effects on the electrophysiological activity of the brain in healthy individuals.