ArticleLiterature Review

Can transcranial photobiomodulation improve cognitive function? A systematic review of human studies

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Abstract

Background Transcranial photobiomodulation (tPBM) has been studied for over a decade as a possible cognitive intervention. Objective To evaluate the effect of tPBM for enhancing human cognitive function in healthy adults and remediating impaired cognitive function in adults with cognitive disorders. Methods A systematic literature search from three electronic databases (PubMed, Scopus, Web of Science) was conducted from 1987 to May 2022. The cognitive function being evaluated included learning and memory, attention, executive function, language, and global cognitive function. Results Of the 35 studies identified, 29 (82.9%) studies reported positive improvement in cognitive functions after tPBM. All nine studies on participants with subjective memory complaints, mild cognitive impairment, and dementia, showed positive outcomes. Seven (87.5%) studies on traumatic brain injury (TBI) patients also showed positive results. A series of clinical trials on stroke patients showed positive trends on improved neurological deficit at first, but was prematurely terminated later at phase III due to the lack of statistical significance. One of the most common protocols for clinical populations employed devices delivering near-infrared light (810 nm), the irradiance of 20 – 25 mW/cm², and fluence of 1 – 10 J/cm². While this was common, the reviewed protocols also included other wavelengths of light ranging from visible, red (630 – 635 nm) to invisible near-infrared maximum wavelengths of 1060 – 1068 nm. Conclusions tPBM seems to improve cognitive function. However, only half of the reviewed clinical trials were randomized control trials, further investigation is warranted.

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... Thus, behavior-based interventions generally appear to produce limited improvements in the frontal lobe cognitive functions of normal older adults. In view of this, there is increasing interest in applying transcranial photobiomodulation (tPBM) as a possible efficient and non-invasive intervention for improving cognitive functions in either normal or clinical populations (for a review, see Chan et al., 2019b;Lee et al., 2022). Previous studies on normal young and older adults have consistently reported that tPBM can significantly improve various aspects of cognitive functions primarily mediated by the frontal lobe, including set-shifting (Blanco et al., 2017a), rule-based category learning (Blanco et al., 2017b), sustained attention (Barrett and Gonzalez-Lima, 2013;Moghadam et al., 2017;Vargas et al., 2017), and working memory (Barrett and Gonzalez-Lima, 2013;Vargas et al., 2017). ...
... Although some studies of tPBM suggest that this intervention seems to have positive effects on the frontal lobe cognitive functions of normal adults and patients with traumatic brain injury (Lee et al., 2022), and depressive and anxiety symptoms in patients with psychological disorders (Gutiérrez-Menéndez et al., 2020), its effect on older adults with mild cognitive impairment (MCI) of the non-amnestic type remains unknown. In this study, we investigated the effect of tPBM on three older adults with non-amnestic MCI who demonstrated impairment in the frontal lobe cognitive functions and depressive and anxiety symptoms at baseline. ...
... In this study, we investigated the effect of tPBM on three older adults with non-amnestic MCI who demonstrated impairment in the frontal lobe cognitive functions and depressive and anxiety symptoms at baseline. Given the positive effects of tPBM on improving inhibitory control and mental flexibility (functions mediated by the frontal lobe) of normal older adults in our recent study (Chan et al., 2019a), and the use of tPBM in improving the frontal lobe cognitive functions of patients with traumatic brain injury (TBI) (Naeser et al., 2011(Naeser et al., , 2014(Naeser et al., , 2016Lee et al., 2022) and depressive and anxiety symptoms in clinical patients (Gutiérrez-Menéndez et al., 2020), we anticipated that tPBM stimulation would improve the frontal lobe cognitive functions, and depressive and anxiety symptoms of older adults with non-amnestic MCI. These case studies may provide preliminary support for the potential of tPBM as an intervention for individuals with non-amnestic MCI or cognitive dysfunction associated with the frontal lobe. ...
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Introduction This study investigated the effects of transcranial photobiomodulation (tPBM) on improving the frontal lobe cognitive functions and mental health of older adults. Methods Three older adults with mild cognitive impairment (MCI) of the non-amnestic type received 18-session tPBM stimulation for 9 weeks and were assessed with neuropsychological tests of memory and executive functions and standardized questionnaires on depressive and anxiety symptoms, global cognitive functions, and daily functioning abilities before and after tPBM stimulation. Results At baseline, their intrusion and/or perseveration errors in a verbal memory test and a fluency test, as measures of the frontal lobe cognitive functions, were in the borderline to severely impaired range at baseline. After tPBM stimulation, the three older adults showed various levels of improvement in their frontal lobe cognitive functions. One older adult’s intrusion and perseveration errors improved from the <1st–2nd percentile (moderately to severely impaired range) to the 41st–69th percentile (average range), another older adult’s intrusion errors improved from the 11th percentile to the 83rd percentile, and the third older adult’s intrusion errors improved from the 5th percentile to the 56th percentile. Moreover, improvements in their anxiety and/or depressive symptoms were also observed. One older adult’s depressive and anxiety symptoms improved from the severe range at baseline to the mild range after the intervention. The other two older adults’ depressive symptoms improved from the mild range at baseline to the normal range after the intervention. Discussion These findings provide preliminary support for the potential of tPBM to improve the frontal lobe cognitive functions and mental health of older adults with MCI. Given the small sample size of only three older adults and the absence of a placebo control group, larger randomized controlled studies are needed to confirm its potential.
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Transcranial infrared laser stimulation (TILS) is a novel, safe, non-invasive method of brain photobiomodulation. Laser stimulation of the human prefrontal cortex causes cognitive enhancement. To investigate the hemodynamic effects in prefrontal cortex by which this cognitive enhancement occurs, we used functional near-infrared spectroscopy (fNIRS), which is a safe, non-invasive method of monitoring hemodynamics. We measured concentration changes in oxygenated and deoxygenated hemoglobin, total hemoglobin and differential effects in 18 healthy adults during sustained attention and working memory performance, before and after laser of the right prefrontal cortex. We also measured 16 sham controls without photobiomodulation. fNIRS revealed large effects on prefrontal oxygenation during cognitive enhancement post-laser and provided the first demonstration that cognitive enhancement by transcranial photobiomodulation is associated with cerebrovascular oxygenation of the prefrontal cortex. Sham control data served to rule out that the laser effects were due to pre-post task repetition or other non-specific effects. A laser-fNIRS combination may be useful to stimulate and monitor cerebrovascular oxygenation associated with neurocognitive enhancement in healthy individuals and in those with prefrontal hypometabolism, such as in cognitive aging, dementia and many neuropsychiatric disorders.
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Purpose To systematically review the literature and update the evidence-based clinical practice guidelines for the use of photobiomodulation (PBM), such as laser and other light therapies, for the prevention and/or treatment of oral mucositis (OM). Methods A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) using PubMed and Web of Science. We followed the MASCC methods for systematic review and guidelines development. The rigorously evaluated evidence for each intervention, in each cancer treatment setting, was assigned a level-of-evidence (LoE). Based on the LoE, one of the following guidelines was determined: Recommendation, Suggestion, or No Guideline Possible. Results Recommendations are made for the prevention of OM and related pain with PBM therapy in cancer patients treated with one of the following modalities: hematopoietic stem cell transplantation, head and neck (H&N) radiotherapy (without chemotherapy), and H&N radiotherapy with chemotherapy. For each of these modalities, we recommend 1–2 clinically effective protocols; the clinician should adhere to all parameters of the protocol selected. Due to inadequate evidence, currently, No Guideline Possible for treatment of established OM or for management of chemotherapy-related OM. The reported clinical settings were extremely variable, limiting data integration. Conclusions The evidence supports the use of specific settings of PBM therapy for the prevention of OM in specific patient populations. Under these circumstances, PBM is recommended for the prevention of OM. The guidelines are subject to continuous update based on new published data.
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The aim of the present study was to investigate the electrophysiological effects of the photobiomodulation (PBM) by the quantitative electroencephalography (qEEG) as a diagnostic method. The neurotherapeutic potential of transcranial PBM has been recently investigated in preclinical and clinical studies. According to the PBM mechanisms of action on increasing the cerebral blood flow and the neuronal firing, a change may occur in cortical electrical activity after transcranial PBM that could be revealed in qEEG. A total of 30 participants (15 males and 15 females) were included in this experimental study in a convenience sampling method. A 19-channel EEG was obtained from subjects, before and after receiving sham or real 850-nm PBM by light emitting diode (LED) array on the right prefrontal cortex (PFC). An attentional task also was completed by the participant before and after the irradiation. Results presented that the effect of PBM on the reaction time was significant (p = 0.001) in favor of the real-treatment group (p < 0.05). For the absolute power, repeated-measures ANOVA showed a significant interaction of group × time × frequency (p = 0.04). In the real-treatment group, absolute power of delta band was significantly reduced in all electrodes (p < 0.05). Also, a similar significant interaction of group × time × frequency was seen for relative power (p = 0.04). Post-hoc analysis showed a significant decrease in delta band after PBM in the real treatment group (p < 0.05). The study presented that light irradiation with 850-nm LED source on right PFC could change brain electrical activity and has beneficial effects on attentional performance.
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General purpose: To provide background and examine evidence for the therapeutic application of light energy treatments for wound healing. Target audience: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. Learning objectives/outcomes: After completing this continuing education activity, you should be better able to:1. Explain the basics of lasers, light-emitting diodes, and light-tissue interactions as they apply to photobiomodulation therapy.2. Summarize the results of the authors' literature review of the evidence regarding the therapeutic applications of photobiomodulation treatments for wound healing. Abstract: To provide background and examine evidence for the therapeutic applications of light energy treatments for wound healing.A search was performed in PubMed for peer-reviewed scientific articles published in the last 5 years using the search terms "photobiomodulation therapy" and "low-level laser therapy," and these terms combined with "wound," using a "human species" filter. This search yielded 218 articles on photobiomodulation therapy or low-level laser therapy and wounds. Of these, only articles on in vivo wound care using light treatments were specifically included in this review (n = 11).The wound healing effects of low-dose laser treatments were first described over 50 years ago. Various doses ranging from 0.1 to 10 J/cm and wavelengths ranging from 405 to 1,000 nm appear to provide therapeutic benefits for a broad range of chronic wounds. A range of light energy sources from LEDs to lasers have been used and have specific advantages and limitations. There is a lack of consensus on standardized treatment parameters such as wavelengths, dose, and therapeutic outcomes in the reviewed studies, preventing direct comparison and clinical protocol recommendation. An expert opinion based on ongoing research studies and reported literature is offered.Noninvasive, economical, and multipurpose light devices are an attractive tool for wound management. However, there is an urgent need in the wound care community to develop optimal clinical protocols for use based on well-designed, rigorous clinical research studies.
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Cerebrovascular accidents (CVAs), commonly known as strokes, can damage the brain through vascular injuries caused by either blood vessel blockages (ischemic stroke) or ruptures (hemorrhagic stroke) which disrupt regular brain blood supply and can cause severe damage to the individual. The objective of the present study was to evaluate the effects of photobiomodulation with a light-emitting diode (LED) device (904 nm, 110 mW, 7 J/cm²) on neurogenesis, muscle resistance, and motor behavior in animals submitted to an experimental model of hemiplegia. The sample consisted of 30 Wistar rats, divided into two groups: control group (GC) and 904-nm LED-treated group (TG). All animals underwent stereotactic surgery for electrode implant and subsequent electrolytic injury to induce an ischemic stroke. TG was subjected to daily LED irradiation (904 nm, 110 mW, 7 J/cm²) for 63 s. Suspension test results indicate an improvement of TG muscle resistance when compared with baseline evaluation (BLT); a reduction in open-field freezing time and the number of fecal bolus pellets suggest diminished anxiety induced by 904-nm LED treatment on treatment days 7 and 21 (TG7 and TG21) compared with the baseline results; and lastly, histological analysis showed important signs of neurogenesis in TG in comparison to CG, especially on treatment days 7 and 21 (TG7 and TG21). In conclusion, the present study suggests that 904-nm LED irradiation may beneficially affect neurogenesis, muscle resistance, and animal motor behavior following ischemic CVA.
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Photobiomodulation (PBM) therapy, previously known as low-level laser therapy, was discovered more than 50 years ago, yet there is still no agreement on the parameters and protocols for its clinical application. Some groups have recommended the use of a power density less than 100mW/cm 2 and an energy density of 4 to 10J/cm 2 at the level of the target tissue. Others recommend as much as 50J/cm 2 at the tissue surface. The wide range of parameters that can be applied (wavelength, energy, fluence, power, irradiance, pulse mode, treatment duration, and repetition) in some cases has led to contradictory results. In our review, we attempt to evaluate the range of effective and ineffective parameters in PBM. Studies in vitro with cultured cells or in vivo with different tissues were divided into those with higher numbers of mitochondria (muscle, brain, heart, nerve) or lower numbers of mitochondria (skin, tendon, cartilage). Graphs were plotted of energy density against power density. Although the results showed a high degree of variability, cells/tissues with high numbers of mitochondria tended to respond to lower doses of light than those with lower number of mitochondria. Ineffective studies in cells with high mitochondrial activity appeared to be more often due to over-dosing than to under-dosing. © © 2018 Society of Photo-Optical Instrumentation Engineers (SPIE).
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Background Photobiomodulation is widely studied for its potential benefits in the wound healing process. Numerous scientific studies have highlighted its effect on various phases of wound repair, but clinical validations are few. This comparative trial aims to evaluate the influence of photobiomodulation on the post-abdominoplasty healing process. Methods Seventeen Caucasian women (aged 18–55) who underwent an abdominoplasty were enrolled in this double-blinded, controlled clinical trial. The postoperative scars were divided into two areas; the right side of the scars was treated with ten sessions of photobiomodulation (consisting in three types of wavelengths). The other part of the scars was used as control and did not receive any additional treatment. Clinical assessments of both parts of the scars were scheduled at 1, 6 and 12 months postoperative. Results Within six months following surgery, significantly improved quality of the scars on the treated side compared with the untreated side was reported by patients and experienced professionals according to Vancouver Scar Scale, Patient and Observer Scar Assessment Scale (p < 0.05) and standardized photographs (p < 0.05). At 1 year of follow-up, patients observed no differences between the treated and untreated sides of the scars. This suggests that photobiomodulation appears to play an early role in the wound healing process, accelerating the first stages of cicatrization. Conclusion This study statistically validates the positive impact of photobiomodulation treatment on the first stages of the postoperative healing process. Carried out on Caucasians participants only, this study should, however, be performed on a more heterogeneous population to definitively confirm these effects on an international population. Clinical trial registry Registro Brasileiro de ensaios clínicos: http://www.ensaiosclinicos.gov.br, Trial RBR-49PK78. Level of Evidence II This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Objectives The frontal lobe hypothesis of age‐related cognitive decline suggests that the deterioration of the prefrontal cortical regions that occurs with aging leads to executive function deficits. Photobiomodulation (PBM) is a newly developed, non‐invasive technique for enhancing brain function, which has shown promising effects on cognitive function in both animals and humans. This randomized, sham‐controlled study sought to examine the effects of PBM on the frontal brain function of older adults. Methods/Designs Thirty older adults without a neuropsychiatric history performed cognitive tests of frontal function (i.e., the Eriksen flanker and category fluency tests) before and after a single 7.5‐min session of real or sham PBM. The PBM device consisted of three separate light‐emitting diode cluster heads (633 nm and 870 nm), which were applied to both sides of the forehead and posterior midline, and delivered a total energy of 1349 J. Results Significant group (experimental, control) × time (pre‐PBM, post‐PBM) interactions were found for the flanker and category fluency test scores. Specifically, only the older adults who received real PBM exhibited significant improvements in their action selection, inhibition ability, and mental flexibility after vs. before PBM. Conclusions Our findings support that PBM may enhance the frontal brain functions of older adults in a safe and cost‐effective manner.
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Background To observe the effect of red light phototherapy (RLPT) on radioactive dermatitis (RD) caused by radiotherapy in patients with head and neck cancer (HNC). Methods Sixty patients with HNC admitted to our hospital were randomly divided into experimental group and control group, 30 patients in each group. The control group received routine daily care during radiotherapy treatment. In the experimental group, in addition to routine daily care during radiotherapy treatment, photon therapy apparatus RLPT was added, 10 min/time, 2 times/day, and lasted until the end of radiotherapy. The pain and conditions of the patients’ skin were assessed daily, and the skin pain and dermatitis grades of the two groups were compared. Results In terms of the reaction degree of RD, experimental group was mainly grade 0–2, and control group was mainly grade 2–3, with a significant difference (P < 0.05). In terms of skin pain, according to the pain records at week 2, 3, and 4, the pain degree increased with time. However, the score of wound pain in experimental group was significantly lower than that in control group, and there was a significant difference between the two groups (P < 0.05). Conclusions The application of RLPT in the treatment of RD can help accelerate wound healing and significantly shorten healing time. It can not only reduce wounds pain of patients, promote inflammation and ulcer healing, but also ensure the smooth progress of patients’ radiotherapy and improve their quality of lives, which is worth popularization and application in the clinical practice.
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Oral squamous cell carcinoma (OSCC) is the most frequent oral malignant neoplasia. As consequence of OSCC treatment, oral mucositis (OM) is one of the most common adverse effects of OSCC treatment. Currently, there is no consensus for OM treatment. The purpose of the current study was to test the combination of red and infrared low-level laser therapy (LLLT) for OM treatment. Primary culture of human fibroblast was performed to identify LLLT dose. After laboratory tests, a two-arm parallel, single-blind, controlled study was conducted. The two arms were group 1, both 660- and 808-nm wavelengths (300 J/cm2, 9 J of total energy, 100 mW, spot size 3 mm2), and group 2, only 660-nm wavelength (300 J/cm2, 9 J of total energy, 100 mW, spot size 3 mm2). Both treatments were performed twice a week. Group 1 presented a reduction of mucositis grade in comparison to group 2. Group 1 also presented reduction of analgesics prescription. But no significant differences between groups 1 and 2 were observed according to the pain scale. In conclusion, the current study demonstrated that a combination of red and infrared at a higher dose (300 J/cm2) reduced both oral mucositis grade and analgesics prescription. The effects of the combination of RT and LLLT are unclear and need more studies.
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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 Ca²⁺ 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.
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Transcranial infrared laser stimulation (TILS) at 1064 nm, 250 mW/cm² has been proven safe and effective for increasing neurocognitive functions in young adults in controlled studies using photobiomodulation of the right prefrontal cortex. The objective of this pilot study was to determine whether there is any effect from TILS on neurocognitive function in older adults with subjective memory complaint at risk for cognitive decline (e.g., increased carotid artery intima-media thickness or mild traumatic brain injury). We investigated the cognitive effects of TILS in older adults (ages 49–90, n = 12) using prefrontal cortex measures of attention (psychomotor vigilance task (PVT)) and memory (delayed match to sample (DMS)), carotid artery intima-media thickness (measured by ultrasound), and evaluated the potential neural mechanisms mediating the cognitive effects of TILS using exploratory brain studies of electroencephalography (EEG, n = 6) and functional magnetic resonance imaging (fMRI, n = 6). Cognitive performance, age, and carotid artery intima-media thickness were highly correlated, but all participants improved in all cognitive measures after TILS treatments. Baseline vs. chronic (five weekly sessions, 8 min each) comparisons of mean cognitive scores all showed improvements, significant for PVT reaction time (p < 0.001), PVT lapses (p < 0.001), and DMS correct responses (p < 0.05). The neural studies also showed for the first time that TILS increases resting-state EEG alpha, beta, and gamma power and promotes more efficient prefrontal blood-oxygen-level-dependent (BOLD)-fMRI response. Importantly, no adverse effects were found. These preliminary findings support the use of TILS for larger randomized clinical trials with this non-invasive approach to augment neurocognitive function in older people to combat aging-related and vascular disease-related cognitive decline.
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Background: Transcranial light therapy (TCLT) is a new noninvasive interventional method, which applies red to near infrared spectrum laser or light emitting diode (LED) source on the head, transcranially. This spectrum can penetrate the skull and could improve the brain pathological conditions and cognitive functions. Despite relative advantages of the LED upon laser sources, TCLT research has been limited on the beneficial effects of LED source on human cognitive performances. Objectives: This study aimed at investigating the effectiveness of the TCLT with LED source on brain attentional performance as an important cognitive ability. Methods: This experimental intervention study was conducted in Tabriz, Iran, from September to October 2016. The study samples were selected by the convenience sampling method. Thirty-four healthy individuals (age: 18 to 24; 17 males and 17 females) were randomly assigned to sham (n = 17) or real intervention (n = 17) groups. We applied 850 nm LED with irradiation energy density 60 J/cm² upon the frontal cortex, the brain region involved in attentional activities. Before and after TCLT, participants completed a cognitive task (Level-1 of parametric Go/No-task), which measures attentional performance. Results: Our results revealed improvement of efficiency score as the main parameter of attentional performance in the real intervention group versus sham-TCLT group. The interaction of group × time was significant (P = 0.004). Mean change of the efficiency score was higher in the real intervention group (mean = 4.6 ± 3) than the sham group (mean = 0.8 ± 3) after TCLT (P = 0.001). Conclusions: Applying the TCLT by LED source over the PFC, promotes attentional performance as an important cognitive function.
Article
Objective: To assess the efficacy and safety of transcranial photobiomodulation (tPBM) in adults with autism spectrum disorder (ASD). Methods: Adults with high-functioning-ASD, between 18 and 59 years of age, were enrolled to receive twice a week tPBM for 8 weeks in an open-label single group design. ASD symptom severity was assessed at baseline, midpoint, and end-point, by clinician-, self-, and informant-rated measures. Treatment response was defined as a ≥30% reduction in Social Responsiveness Scale-2nd Edition (SRS-2) total score and ASD Clinical Global Impression-Improvement score ≤2. Any possible adverse events were recorded at each visit. Paired-samples t-test analyses were performed. Results: Eleven participants were enrolled, and 10 participants (9 males; 30.0 ± 11.9 years) completed the study. One participant withdrew consent before baseline. All 10 completers were included in efficacy and safety analyses. Five participants (50%) met responder criteria at end-point. Overall, 8-week tPBM was associated with significant reduction in SRS-2 total scores at end-point (SRS-2: -30.6 ± 23, p < 0.001) particularly in Social Awareness (-3.0 ± 1.9, p < 0.001), Social Communication (-10.3 ± 6, p < 0.001), Social Motivation (-5.0 ± 2.4, p < 0.001), and Restricted/Repetitive Behaviors (-7.4 ± 4.1, p < 0.001). There were statistically significant improvements at end-point in Global Assessment of Functioning scores (+12.8 ± 4.2, p < 0.001) and Quality of Life Enjoyment and Satisfaction Questionnaire scores (+6.0 ± 7.9, p = 0.02). Three participants experienced transient, mild side effects (insomnia, headache, and warmth at treatment application site). No adverse events required changes in tPBM protocol. Adherence rate was 98%. Conclusions: tPBM is a safe and feasible treatment approach that has the potential to treat core features of ASD. Further research is necessary and warranted. ClinicalTrials.gov Identifier: NCT03724552.
Article
Background: We present a pilot study of near-infrared (NIR) 1068 nm transcranial photobiomodulation therapy (PBM-T). Impact upon motor function, memory, and processing speed in healthy individuals, older than 45 years of age, was evaluated. Methods: PBM-T was performed at home using a transcranial phototherapy device, a helmet that comprised 14 air cooled light emitting diode panel arrays, with a peak wavelength of 1068 nm, full width at half maximum bandwidth of 60 nm and total average optical output power of 3.8 W. The device was used for 6 min twice daily on age-matched middle-aged subjects with normal intellectual function. The US Food and Drug Administration (FDA)-approved computerized assessment tool Automated Neuropsychological Assessment Metrics (ANAM) was adopted to quantify a series of cognitive and motor activities in the participating groups. Results: A significant improvement in motor function, memory performance, and processing speed was observed in healthy individuals with PBM-T compared to the placebo group. No adverse effects were reported. Conclusions: PBM-T may be a promising new approach to improve memory in healthy middle-aged individuals. ClinicalTrials.gov ID: NCT04568057.
Article
Background: Neuroprotection against Parkinson's disease degeneration by photobiomodulation has been reported in animal models but no true placebo-controlled human studies have been published. Objective: To understand if photobiomodulation therapy can produce clinically significant differences in physical performance measures in people with Parkinson's disease; and what frequency of treatment is necessary to initiate clinical change. Methods: In a participant and assessor-blinded, randomized, placebo-controlled pilot study, 22 participants received either sham and/or active laser photobiomodulation (904 nm, 60 mW/diode, 50 Hz) for 33 s to each of 21 points at the cranium and intra-orally, on one, two or three times/week for 4 weeks. Two treatment phases were separated by a 4-week wash-out (Phase 2). Upper and lower limb physical outcome measures were assessed before and after each treatment phase. The Montreal Cognitive Assessment was evaluated prior to treatment Phase 1, and at the end of treatment Phase 3. Results: Montreal Cognitive Assessment remained stable between start and end of study. No measures demonstrated statistically significant changes. With regular treatment, the spiral (writing) test and the dynamic step test were most sensitive to change in a positive direction; and the 9-hole peg test demonstrated a minimum clinically important difference worthy of further investigation in a larger, adequately powered clinical trial. A placebo effect was noted. Conclusion: The results support the notion that combined transcranial and intra-oral photobiomodulation therapy needs to be applied at least 2 to 3 times per week for at least four weeks before some improvement in outcome measures becomes evident. Longer courses of treatment may be required.
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Stroke is the main cause of death and functional disability. The available therapy affects only 5% of patients, and new therapeutic approaches have been constantly tested. Transcranial photobiomodulation (PBM) is promising for its neuroprotective effect on brain injuries. Thus, the present study investigated the PBM effects in an in vivo model of ischemic stroke induced by photothrombosis (PT). Five different groups of Wistar rats were submitted or not to a daily dose of fish oil or/and laser sessions for 2 months. The ischemia volume was evaluated by stereology; GFAP, Iba, and NeuN by immunohistochemistry; TNF‐α, IL‐1β, IL‐6, IL‐10, and TGF‐β by ELISA assay. PBM influenced both the lesion volume and the GFAP. Furthermore, PBM and Ω‐3 or both reduced Iba RNAm. PBM reduced TNF‐α, IL‐1β, IL‐6, brain damage, neuroinflammation, and microglial activation, and it increased astroglial activity in peri‐lesioned region after stroke. This article is protected by copyright. All rights reserved.
Article
Photobiomodulation, otherwise known as low‐level laser (or light) therapy, is an emerging modality for the management of hair loss. Several randomized trials have demonstrated that it is safe and potentially effective on its own or in combination with standard therapies. These devices come in many forms including wearable caps or helmets that afford hands‐free and discreet use. Models with light‐emitting diodes (LEDs) are less expensive compared to laser‐based devices and do not require laser safety considerations, thus facilitating ease of home use. Limitations include cost of the unit, risk of information bias, and lack of standardized protocols. Finally, as with any hair loss treatment, patients’ expectations with regards to therapeutic outcomes must be managed.
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Significance: Accumulating evidence suggests that inflammation is a major contributor in the pathogenesis of several highly prevalent, but also rare, neurological diseases. In particular, the neurodegenerative processes of Alzheimer disease (AD), vascular dementia (VAD), Parkinson's disease (PD), multiple sclerosis (MS) are fueled by neuroinflammation, which in turn is accompanied by a parallel systemic immune dysregulation. This cross-talk between periphery and the brain becomes substantial when the blood brain barrier loses its integrity as often occurs in the course of these diseases. It has been hypothesized the perpetual bidirectional flux of inflammatory mediators is not a mere "static" collateral effect of the neurodegeneration, but represents a proactive phenomenon sparking and driving the neuropathological processes. However, the upstream/downstream relationship between inflammatory events and neurological pathology is still unclear. Recent advances: Solid recent evidence clearly suggest that metabolic factors, systemic infections, Microbiota dysbiosis, and oxidative stress are implicated, although at different extent, in the development in brain diseases CRITICAL ISSUE: Here, we reviewed the most solid published evidence supporting the implication of the axis systemic inflammation-neuroinflammation-neurodegeneration in the pathogenesis of AD, VAD, PD and MS, highlighting the possible cause of the putative downstream component of the axis. Future directions: Reaching a definitive clinical/epidemiological appreciation of the etiopathogenic significance of the connection between peripheral and brain inflammation in neurologic disorders is pivotal since it could open novel therapeutic avenues for these diseases.
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Neurological disorders are the leading cause of disability and the second leading cause of death worldwide. In the past 30 years, the absolute numbers of deaths and people with disabilities owing to neurological diseases have risen substantially, particularly in low-income and middle-income countries, and further increases are expected globally as a result of population growth and ageing. This rise in absolute numbers of people affected suggests that advances in prevention and management of major neurological disorders are not sufficiently effective to counter global demographic changes. Urgent measures to reduce this burden are therefore needed. Because resources for health care and research are already overstretched, priorities need to be set to guide policy makers, governments, and funding organisations to develop and implement action plans for prevention, health care, and research to tackle the growing challenge of neurological disorders.
Article
Literature databases (i.e., PubMed, Scopus, and Web of Science) differ in terms of their coverage, focus, and the tool they provide. PubMed focuses mainly on life sciences and biomedical disciplines, whereas Scopus and Web of Science are multidisciplinary. The protocol described in the current study was used to search for publications from Jordanian authors in the years 2013-2017. In this protocol, how to use each database to conduct this type of search is explained in detail. A Scopus search resulted in the highest number of documents (11,444 documents), followed by a Web of Science search (10,943 documents). PubMed resulted in a smaller number of documents due to its narrower scope and coverage (4,363 documents). The results also show a yearly trend in: (1) the number of publications, (2) the disciplines that have the most publications, (3) the countries of collaboration, and (4) the number of open access publications. In contrast, PubMed has a sophisticated keyword optimization service (i.e., Medical Subject Heading, or MeSH), while both Scopus and Web of Science provide search analysis tools that can produce representative figures. Finally, the features of each database are explained in detail and several indices that can be extracted using the search results are provided. This study provides a base for using literature databases for bibliometric analysis.
Article
Background: Transcranial photobiomodulation (t-PBM) is a noninvasive modality that may improve cognitive function in both healthy and diseased subjects. Objective: This systematic review and meta-analysis addresses the question of whether t-PBM improves cognitive function in healthy adults. Methods: We searched MEDLINE using PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane Library up to March 2019. We also searched ProQuest and Google Scholar databases for unpublished material. The search was limited to articles on the procognitive effects of t-PBM in healthy adults. The initial search resulted in 871 studies, of which nine publications met our criteria for inclusion and exclusion. Seven studies were performed on young, healthy subjects (17–35 years), and two studies were conducted on older (‡49 years), normal subjects. A meta-analysis was performed on six full-text publications whose subjects were young adults. Results: t-PBM administration improved cognition-related outcomes by an 0.833 standardized mean difference (SMD; 95% confidence interval (CI): 0.458–1.209, 14 comparisons) in young, healthy participants. Funnel plotting revealed asymmetry, which was validated using Egger’s ( p = 0.030) and Begg’s regression ( p = 0.006) tests. However after reanalysis, this asymmetry disappeared in the attention subgroup, but not in the memory subgroup. The trim-and-fill analysis indicated two studies were lacking required data. Thus, the effect size was adjusted from an SMD of 0.761 (95% CI: 0.573–0.949) to 0.949 (0.779–1.120). The overall quality score of the studies was modest. Conclusions: We demonstrated a significant, beneficial effect of t-PBM on cognitive performance of young, healthy individuals; however, the heterogeneity of the data was high. This could be due to the modest quality or to the low number of included studies, or to the differences between the various subdomains assessed. These shortcomings should be meticulously addressed before concluding that t-PBM is a cognitive-enhancing intervention in healthy individuals.
Chapter
Converging evidence suggests that human aging is associated with structural, functional, and cognitive deteriorations that preferentially affect the frontal lobe of the brain. Because a decline in frontal cognitive functions may be associated with subsequent declines in global cognitive function and functional activities, interventions that effectively enhance frontal lobe functions of older adults are clinically important. In this chapter, we propose that photobiomodulation (PBM) can be an effective treatment option to protect the aging neurons and enhance frontal lobe functions in normal older adults. Specifically, aging is associated with frontal hypometabolism; through its effects on mitochondrial functioning, PBM may increase energy production and oxygen supply to support metabolism of the aging neurons. In addition, aging is associated with neural atrophy and loss of synapses; through its effects on transcription factors, PBM may promote neuronal survival and encourage the formation of new cells and synapses in the aging frontal cortex.
Article
Objective: To examine the effects of transcranial and intranasal photobiomodulation (PBM) therapy, administered at home, in patients with dementia. Background: This study sought to replicate and build upon a previously published case series report describing improved cognitive function in five patients with mild-to-moderate dementia after 12 weeks of transcranial and intranasal near-infrared (NIR) PBM therapy. Materials and methods: Eight participants (mean age: 79.8 ± 5.8 years old) diagnosed with dementia by their physicians were randomized to 12 weeks of usual care (UC, n = 4) or home PBM treatments (n = 4). The NIR PBM treatments were administered by a study partner at home three times per week with the Vielight Neuro Gamma device. The participants were assessed with the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog) subscale and the Neuropsychiatric Inventory (NPI) at baseline and 6 and 12 weeks, and with arterial spin-labeled perfusion magnetic resonance imaging (MRI) and resting-state functional MRI at baseline and 12 weeks. Results: At baseline, the UC and PBM groups did not differ demographically or clinically. However, after 12 weeks, there were improvements in ADAS-cog (group × time interaction: F1,6 = 16.35, p = 0.007) and NPI (group × time interaction: F1,6 = 7.52, p = 0.03), increased cerebral perfusion (group × time interaction: F1,6 = 8.46, p < 0.03), and increased connectivity between the posterior cingulate cortex and lateral parietal nodes within the default-mode network in the PBM group. Conclusions: Because PBM was well tolerated and associated with no adverse side effects, these results support the potential of PBM therapy as a viable home treatment for individuals with dementia.
Article
Objective: This study explored the outcome of applying red/near-infrared light therapy using light-emitting diodes (LEDs) pulsed with three different frequencies transcranially to treat traumatic brain injury (TBI) in Veterans. Background: Photobiomodulation therapy (PBMT) using LEDs has been shown to have positive effects on TBI in humans and animal models. Materials and methods: Twelve symptomatic military Veterans diagnosed with chronic TBI >18 months post-trauma received pulsed transcranial PBMT (tPBMT) using two neoprene therapy pads containing 220 infrared and 180 red LEDs, generating a power output of 3.3 W and an average power density of 6.4 mW/cm2 for 20 min, thrice per week over 6 weeks. Outcome measures included standardized neuropsychological test scores and qualitative and quantitative single photon emission computed tomography (SPECT) measures of regional cerebral blood flow (rCBF). Results: Pulsed tPBMT significantly improved neuropsychological scores in 6 of 15 subscales (40.0%; p < 0.05; two tailed). SPECT analysis showed increase in rCBF in 8 of 12 (66.7%) study participants. Quantitative SPECT analysis revealed a significant increase in rCBF in this subgroup of study participants and a significant difference between pre-treatment and post-treatment gamma ray counts per cubic centimeter [t = 3.77, df = 7, p = 0.007, 95% confidence interval (95,543.21-21,931.82)]. This is the first study to report quantitative SPECT analysis of rCBF in regions of interest following pulsed tPBMT with LEDs in TBI. Conclusions: Pulsed tPBMT using LEDs shows promise in improving cognitive function and rCBF several years after TBI. Larger, controlled studies are indicated.
Article
Objective: We present a case report of rapid reversal of cognitive impairment, olfactory dysfunction and quality of life measures in a patient with cognitive decline after multi-modality photobiomodulation (PBM) therapy. Background: Transcranial and intranasal PBM has been introduced as a light-based therapeutic technique in which exposure to low-levels of red to near-infrared light stimulates neuronal function, leading to beneficial neurological effects. Materials and Methods: Patient received 4 weeks of twice-daily PBM therapy at home using three separate light-emitting diode (LED) devices: transcranial/intranasal/body-pad. Results: The patient showed a significant improvement in the Montreal Cognitive Assessment score from 18 to 24 and in the Working Memory Questionnaire score from 53 to 10. The cognitive enhancement was accompanied by reversal of olfactory dysfunction as measured by the Alberta Smell Test and peanut butter odor detection test. Quality of life measures improved and caregiver stress was reduced. No adverse effects were reported. Conclusions: PBM therapy may be a promising non-invasive approach for patients with neurodegenerative diseases.
Article
Orthodontic treatment promotes a degree of discomfort in patients and can lead to them giving up treatment when they have a lower pain tolerance threshold. The aim of this study was to evaluate the low level laser therapy (LLLT) in controlling pain after placement of orthodontic separators. A total of 40 volunteers who were divided into 2 groups: G1 - exposed hemi-arch (LLLT use) and hemi-arch G2 (simulation). Orthodontic tabs were placed in the upper first molar and immediately the laser or simulation was performed. During the use of the separators, the volunteers recorded visual analogue scale in the periods (T0) 5 min, 24 h (T1) and 120 h (T2) after the procedure to evaluate the intensity of pain. After the evaluation sessions, each volunteer was asked to complete a scale to evaluate their satisfaction regarding the use of laser in pain control (LIKERT scale). Differences between G1 and G2 were observed for all the evaluated intervals (T0, T1 and T2), presenting a greater reduction of pain in the hemi-arch exposed to the laser. Regarding sex, a lower pain reduction was observed in males (p > 0.05). Regarding the LIKERT scale, the volunteers demonstrated a high satisfaction rate regarding LLLT use. It was observed a significant reduction in pain from exposed to the laser hemi-arch compared to hemi-arch not exposed at all time intervals assessed. In this way, the results obtained suggest that the use of the reduced pain sensitivity after the placement of orthodontic separators.
Chapter
Photobiomodulation (PBM) or low-level laser (light) therapy (LLLT) describes the use of red or near-infrared light from lasers or LEDs to heal, stimulate, and protect damaged tissues. It was first used for wound healing and pain relief but in recent years has been extensively investigated for brain disorders. One of the first applications of transcranial PBM in the brain was for acute stroke. The mechanisms of action of PBM are multifunctional. PBM applied to the head can increase cerebral blood flow by releasing nitric oxide and improve tissue oxygenation in the brain. It can stimulate mitochondrial metabolism and increase ATP production. Protective mechanisms are activated that can reduce neuronal cell death and oxidative stress occurring as a result of hypoxia, while neuroinflammation is also reduced. PBM can stimulate the formation of new neurons from neuroprogenitor cells in the hippocampus and subventricular zone. Finally, PBM can stimulate synaptogenesis and neuroplasticity (formation of new connections between existing neurons). This chapter will cover animal studies of PBM for acute stroke (caused by a variety of techniques) carried out in rats, rabbits, and dogs. The three major clinical trials for acute stroke in human patients (NEST-1, NEST-2, NEST-3) and the reasons for the eventual failure of NEST-3 will be discussed. Finally, the possibility of using PBM for rehabilitation of chronic stroke patients will be addressed.
Article
Recent work has indicated that photobiomodulation (PBM) may beneficially alter the pathological status of several neurological disorders, although the mechanism currently remains unclear. The current study was designed to investigate the beneficial effect of PBM on behavioral deficits and neurogenesis in a photothrombotic (PT) model of ischemic stroke in rats. From day 1 to day 7 after the establishment of PT model, 2-minute daily PBM (CW, 808nm, 350mW/cm(2), total 294J at scalp level) was applied on the infarct injury area (1.8mm anterior to the bregma and 2.5mm lateral from the midline). Rats received intraperitoneal injections of 5-bromodeoxyuridine (BrdU) twice daily (50mg/kg) from day 2 to 8 post-stoke, and samples were collected at day 14. We demonstrated that PBM significantly attenuated behavioral deficits and infarct volume induced by PT stroke. Further investigation displayed that PBM remarkably enhanced neurogenesis and synaptogenesis, as evidenced by immunostaining of BrdU, Ki67, DCX, MAP2, spinophilin, and synaptophysin. Mechanistic studies suggested beneficial effects of PBM were accompanied by robust suppression of reactive gliosis and the production of pro-inflammatory cytokines. On the contrary, the release of anti-inflammatory cytokines, cytochrome c oxidase activity and ATP production in peri-infarct regions were elevated following PBM treatment. Intriguingly, PBM could effectively switch an M1 microglial phenotype to an anti-inflammatory M2 phenotype. Our novel findings indicated that PBM is capable of promoting neurogenesis after ischemic stroke. The underlying mechanisms may rely on: 1) promotion of proliferation and differentiation of internal neuroprogenitor cells in the peri-infarct zone; 2) improvement of the neuronal microenvironment by altering inflammatory status and promoting mitochondrial function. These findings provide strong support for the promising therapeutic effect of PBM on neuronal repair following ischemic stroke.