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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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Introduction: The quantification of electroencephalography (EEG) microstates is an effective method for analyzing synchronous neural firing and assessing the temporal dynamics of the resting state of the human brain. Transcranial photobiomodulation (tPBM) is a safe and effective modality to improve human cognition. However, it is unclear how prefrontal tPBM neuromodulates EEG microstates both temporally and spectrally. Methods: 64-channel EEG was recorded from 45 healthy subjects in both 8-min active and sham tPBM sessions, using a 1064-nm laser applied to the right forehead of the subjects. After EEG data preprocessing, time-domain EEG microstate analysis was performed to obtain four microstate classes for both tPBM and sham sessions throughout the pre-, during-, and post-stimulation periods, followed by extraction of the respective microstate parameters. Moreover, frequency-domain analysis was performed by combining multivariate empirical mode decomposition with the Hilbert-Huang transform. Results: Statistical analyses revealed that tPBM resulted in (1) a significant increase in the occurrence of microstates A and D and a significant decrease in the contribution of microstate C, (2) a substantial increase in the transition probabilities between microstates A and D, and (3) a substantial increase in the alpha power of microstate D. Discussion: These findings confirm the neurophysiological effects of tPBM on EEG microstates of the resting brain, particularly in class D, which represents brain activation across the frontal and parietal regions. This study helps to better understand tPBM-induced dynamic alterations in EEG microstates that may be linked to the tPBM mechanism of action for the enhancement of human cognition.

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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.

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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 PFC. Overall, this study revealed that tPBM facilitates significant modulation of the directionality of neurophysiological networks in electrophysiological, metabolic, and hemodynamic activities.

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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.

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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.

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Prolonged microgravity exposure causes cognitive impairment. Evidence shows that oxidative stress and neuroinflammation are involved in the causation. Here, we explore the effectiveness of transcranial near-infrared photobiomodulation (PBM) on cognitive deficits in a mouse model of simulated microgravity. 24 adult male C57BL/6 mice were assigned into three groups (8 in each); control, hindlimb unloading (HU), and HU + PBM groups. After surgery to fit the suspension fixing, the animals were housed either in HU cages or in their normal cage for 14 days. The mice in the HU + PBM group received PBM (810 nm laser, 10 Hz, 8 J/cm2) once per day for 14 days. Spatial learning and memory were assessed in the Lashley III maze and hippocampus tissue samples were collected to assess oxidative stress markers and protein expression of brain-derived neurotrophic factor (BDNF), nuclear factor erythroid 2-related factor 2 (Nrf2), Sirtuin 1 (Sirt1), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Behavioral testing showed that the PBM-treated animals had a shorter latency time to find the target and fewer errors than the HU group. PBM decreased hippocampal lipid peroxidation while increasing antioxidant defense systems (glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) compared to HU mice. PBM increased protein expression of Sirt1, Nrf2, and BDNF while decreasing NF-κB compared to HU mice. Our findings suggested that the protective effect of PBM against HU-induced cognitive impairment involved the activation of the Sirt1/Nrf2 signaling pathway, up-regulation of BDNF, and reduction of neuroinflammation and oxidative stress in the hippocampus.

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Transcranial photobiomodulation (tPBM) has been suggested as a non-invasive neuromodulation tool. The repetitive administration of light-emitting diode (LED)-based tPBM for several weeks significantly improves human cognition. To understand the electrophysiological effects of LED-tPBM on the human brain, we investigated alterations by repeated tPBM in vigilance performance and brain networks using electroencephalography (EEG) in healthy participants. Active and sham LED-based tPBM were administered to the right forehead of young participants twice a week for four weeks. The participants performed a psychomotor vigilance task (PVT) during each tPBM/sham experiment. A 64-electrode EEG system recorded electrophysiological signals from each participant during the first and last visits in a 4-week study. Topographical maps of the EEG power enhanced by tPBM were statistically compared for the repeated tPBM effect. A new data processing framework combining the group's singular value decomposition (gSVD) with eLORETA was implemented to identify EEG brain networks. The reaction time of the PVT in the tPBM-treated group was significantly improved over four weeks compared to that in the sham group. We observed acute increases in EEG delta and alpha powers during a 10 min LED-tPBM while the participants performed the PVT task. We also found that the theta, beta, and gamma EEG powers significantly increased overall after four weeks of LED-tPBM. Combining gSVD with eLORETA enabled us to identify EEG brain networks and the corresponding network power changes by repeated 4-week tPBM. This study clearly demonstrated that a 4-week prefrontal LED-tPBM can neuromodulate several key EEG networks, implying a possible causal effect between modulated brain networks and improved psychomotor vigilance outcomes.

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BACKGROUND: Alzheimer's disease's (AD) prevalence is projected to increase as the population ages and current treatments are minimally effective. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates into the cerebral cortex, stimulates the mitochondrial respiratory chain, and increases cerebral blood flow. Preliminary data suggests t-PBM may be efficacious in improving cognition in people with early AD and amnestic mild cognitive impairment (aMCI). METHODS: In this randomized, double-blind, placebo-controlled study with aMCI and early AD participants, we will test the efficacy, safety, and impact on cognition of 24 sessions of t-PBM delivered over 8 weeks. Brain mechanisms of t-PBM in this population will be explored by testing whether the baseline tau burden (measured with 18F-MK6240), or changes in mitochondrial function over 8 weeks (assessed with 31P-MRSI), moderates the changes observed in cognitive functions after t-PBM therapy. We will also use changes in the fMRI Blood-Oxygenation-Level-Dependent (BOLD) signal after a single treatment to demonstrate t-PBM-dependent increases in prefrontal cortex blood flow. CONCLUSION: This study will test whether t-PBM, a low-cost, accessible, and user-friendly intervention, has the potential to improve cognition and function in an aMCI and early AD population.

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Significance: Transcranial photobiomodulation (tPBM) is a noninvasive neuromodulation method that facilitates the improvement of human cognition. However, limited information is available in the literature on the wavelength- and site-specific effects of prefrontal tPBM. Moreover, 2-channel broadband near-infrared spectroscopy (2-bbNIRS) is a new approach for quantifying infra-slow oscillations (ISO; 0.005 to 0.2 Hz) of neurophysiological networks in the resting human brain in vivo. Aim: We aim to prove the hypothesis that the hemodynamic and metabolic activities of the resting prefrontal cortex are significantly modulated by tPBM and that the modulation is wavelength- and site-specific in different ISO bands. Approach: Noninvasive 8-min tPBM with an 800- or 850-nm laser or sham was delivered to either side of the forehead of 26 healthy young adults. A 2-bbNIRS unit was used to record prefrontal ISO activity 7 min before and after tPBM/sham. The measured time series were analyzed in the frequency domain to determine the coherence of hemodynamic and metabolic activities at each of the three ISO frequency bands. Sham-controlled coherence values represent tPBM-induced effects on neurophysiological networks. Results: Prefrontal tPBM by either wavelength and on either lateral side of the forehead (1) increased ipsilateral metabolic-hemodynamic coupling in the endogenic band and (2) desynchronized bilateral activity of metabolism in the neurogenic band and vascular smooth-muscle hemodynamics in the myogenic band. Site-specific effects of laser tPBM were also observed with significant enhancement of bilateral hemodynamic and metabolic connectivity by the right prefrontal 800-nm tPBM. Conclusions: Prefrontal tPBM can significantly modulate neurophysiological networks bilaterally and coupling unilaterally in the human prefrontal cortex. Such modulation effects are site- and wavelength-specific for each ISO band.

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Major depressive disorder (MDD) is considered a global crisis. Conventional treatments for MDD consist of pharmacotherapy and psychotherapy, although a significant number of patients with depression respond poorly to conventional treatments and are diagnosed with treatment-resistant depression (TRD). Transcranial photobiomodulation (t-PBM) therapy uses near-infrared light, delivered transcranially, to modulate the brain cortex. The aim of this review was to revisit the antidepressant effects of t-PBM, with a special emphasis on individuals with TRD. A search on PubMed and ClinicalTrials.gov tracked clinical studies using t-PBM for the treatment of patients diagnosed with MDD and TRD.

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Objective.Transcranial photobiomodulation (tPBM) has shown promising benefits, including cognitive improvement, in healthy humans and in patients with Alzheimer's disease. In this study, we aimed to identify key cortical regions that present significant changes caused by tPBM in the electroencephalogram (EEG) oscillation powers and functional connectivity in the healthy human brain.Approach. A 64-channel EEG was recorded from 45 healthy participants during a 13 min period consisting of a 2 min baseline, 8 min tPBM/sham intervention, and 3 min recovery. After pre-processing and normalizing the EEG data at the five EEG rhythms, cluster-based permutation tests were performed for multiple comparisons of spectral power topographies, followed by graph-theory analysis as a topological approach for quantification of brain connectivity metrics at global and nodal/cluster levels.Main results. EEG power enhancement was observed in clusters of channels over the frontoparietal regions in the alpha band and the centroparietal regions in the beta band. The global measures of the network revealed a reduction in synchronization, global efficiency, and small-worldness of beta band connectivity, implying an enhancement of brain network complexity. In addition, in the beta band, nodal graphical analysis demonstrated significant increases in local information integration and centrality over the frontal clusters, accompanied by a decrease in segregation over the bilateral frontal, left parietal, and left occipital regions.Significance.Frontal tPBM increased EEG alpha and beta powers in the frontal-central-parietal regions, enhanced the complexity of the global beta-wave brain network, and augmented local information flow and integration of beta oscillations across prefrontal cortical regions. This study sheds light on the potential link between electrophysiological effects and human cognitive improvement induced by tPBM.

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