ArticleLiterature Review

Review of transcranial photobiomodulation for major depressive disorder: Targeting brain metabolism, inflammation, oxidative stress, and neurogenesis

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Abstract

We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.

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... The physiological benefits to the brain from tPBM have been the subject of a rich literature of >400 papers on PubMed and several reviews (6)(7)(8)(9)(10). The reviews describe in detail how NIR light is absorbed by cytochrome-C oxidase, which stimulates ATP formation in the mitochondria (11). ...
... The reviews describe in detail how NIR light is absorbed by cytochrome-C oxidase, which stimulates ATP formation in the mitochondria (11). tPBM also increases neurotrophic factors in the brain, increases blood flow, and decreases inflammation (8,12). ...
... In other published tPBM studies no significant side effects have been reported to date (5,8,9,12,37,(42)(43)(44)(45)(46)(47). ...
Article
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Background Opioid use disorders (OUDs) are an epidemic causing catastrophic consequences to individuals, families, and society despite treatments including psychotherapy, substitution therapy or receptor blockers, and psychoeducation. We have developed a novel treatment that combines unilateral transcranial photobiomodulation (t-PBM) to the hemisphere with a more positive valence by Dual Brain Psychology (DBP).Methods We used a randomized, double blind, placebo-controlled protocol in which 22 patients with significant opioid cravings and a history of recent or current OUD attended three 1-h weekly sessions. After baseline measures of opioid craving and other psychometrics, subjects received two unilateral t-PBM applications (810 nm CW LED, 250 mW/cm2, 60 J/cm2, 4 min) or a sham (foil-covered LED) at F3 or F4. Prior to any treatment we used two tests to determine which hemisphere was more associated with a negative outlook and cravings and treated that side before the more positive hemisphere. Primary outcome measure was an opioid craving scale (OCS). Secondary outcomes were weekly Hamilton Depression (HDRS) and Anxiety (HARS) Rating Scales prior to treatments and at follow-up.ResultsImmediately after treatment the OCS improved significantly for both the sham and active treatments, but one week later the active treatment showed a 51.0% (SD 33.7) decrease in OCS while a week after the sham treatments there was a decrease of only 15.8% (SD 35.0) (by Wilcoxon Sign Rank Test, p = 0.004) and by a mixed model it was p = 0.0071. The effect size for the differences between active and sham was 0.73. For the active treatment from before and after treatment the effect size was 1.51 and for the sham, 0.45. The HDRS improved from a baseline of 15.1 to 8.8 (SD 10.3) a week after the active treatment and to 13.3 (SD 12.9) after the sham (p = 0.0071). HARS improved from 14.7 to 8.0 (SD 13.2) after the active treatments and to 14.3 (SD 16.0) after the sham, p = 0.08. Active treatment of the positive hemisphere after the negative hemisphere significantly improved the OCS, but there was no significant difference after the sham treatment. One patient complained of 2 h of abdominal bloating and dropped out; no other adverse effects were observed.DiscussionUnilateral t-PBM to the hemisphere with a more positive hemispheric emotional valence was an effective and safe treatment for opioid cravings as well as for depression and anxiety. Our results also lend support to the underlying premises of DBP.
... Photobiomodulation (PBM) entails the application of low-power, high-fluence light in the red to near-infrared (NIR) range (usually between 630-1100 nm) to modulate mitochondrial respiration in a non-destructive and non-thermal manner. Transcranial PBM (tPBM) refers to PBM directed at the cerebral cortex with the purpose of enhancing cerebral oxygenation and cognitive function [1][2][3][4][5][6]. Approximately 1-2% of NIR light between 660-940 nm penetrates through various layers of the human scalp and skull and reaches the cerebral cortex, several centimeters below the scalp's surface [7,8]. ...
... The purported mechanism of PBM relies on photon absorption by cytochrome-c-oxidase (CCO), which is the terminal enzyme in the mitochondrial respiratory chain that is necessary in cerebral oxygen utilization for energy metabolism. As CCO activity increases, more oxygen is consumed while available metabolic energy increases through simultaneous production of ATP via mitochondrial oxidative phosphorylation [3,4,6]. The resulting increase in CCO activity leads to metabolic and hemodynamic alterations in the brain that can facilitate neuroprotection and cognitive enhancements [9]. ...
... Our previous studies have shown experimental evidence that tPBM is able to enhance oxidized CCO concentration and ∆[HbO] near the stimulation site during and after 8-min tPBM [5,13,49]. It was concluded that this increased metabolic and hemodynamic activity near the light delivery site subsequently results in more oxygen consumption, simultaneous mitochondrial energy production via oxidative phosphorylation, and increased regional cerebral blood flow (rCBF) [3,4,6]. It was unknown whether such a local metabolic/hemodynamic stimulation would affect global cortical networks. ...
Article
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Transcranial photobiomodulation (tPBM) with near-infrared light on the human head has been shown to enhance human cognition. In this study, tPBM-induced effects on resting state brain networks were investigated using 111-channel functional near-infrared spectroscopy over the whole head. Measurements were collected with and without 8-minute tPBM in 19 adults. Functional connectivity (FC) and brain network metrics were quantified using Pearson's correlation coefficients and graph theory analysis (GTA), respectively, for the periods of pre-, during, and post-tPBM. Our results revealed that tPBM (1) enhanced information processing speed and efficiency of the brain network, and (2) increased FC significantly in the frontal-parietal network, shedding light on a better understanding of tPBM effects on brain networks.
... Photobiomodulation (PBM) is a novel treatment under development for major depressive disorder (MDD) and other neuropsychiatric disorders [1]. PBM uses low-power lasers (LPLs) or light-emitting diodes (LEDs) to deliver near-infrared (NIR) or red light aiming to modulate metabolism and functioning of different tissues and organs, including the brain [2]. In the past, lasers were thought to have special biological properties due to their coherence and monochromaticity [3]. ...
... This action of PBM can improve brain hypometabolism and mitochondrial dysfunction associated with depression [9e13]. There is also evidence supporting beneficial effects of PBM in other pathways relevant to MDD including neurogenesis, inflammation, and oxidative stress [2]. Most of the research on PBM for MDD focuses on transcranial PBM (t-PBM) using NIR light. ...
Chapter
Major depressive disorder (MDD) is associated with prefrontal hypometabolism and mitochondrial dysfunction. Photobiomodulation (PBM) is a novel treatment under development for MDD. PBM uses near-infrared (NIR) or red light to modulate metabolism and functioning of different tissues and organs, including the brain. NIR and red light are nonionizing electromagnetic irradiations and can be delivered by noninvasive procedures. Most PBM studies evaluated the direct effect of light on the brain when it is delivered transcranially (t-PBM). However, an indirect effect has also been proposed when light is delivered to other parts of the body (other than the head). The suggested primary mechanism of action of PBM for MDD is the absorption of light energy by a mitochondrial enzyme, the cytochrome C oxidase, resulting in the increase of adenosine triphosphate production. Initial evidence on PBM for MDD indicates it is a safe and effective treatment option.
... Recently, photobiomodulation (PBM) has emerged as a promising treatment for various neurological disorders [9][10][11][12]. Basically, low level red (∼600-700 nm) or near infrared (NIR, 760-1100 nm) light is used in the therapy to preserve, stimulate, and regenerate cells and tissues. ...
... It is commonly accepted that the PBM mechanism is mainly based on promoting mitochondrial activity, thereby affecting the corresponding crucial cell functions [9,14]. In this study, mitochondrial activity of cells in the BBB models rose with an increase in irradiation dose, which suggested that NIR light might affect the BBB permeability through mitochondrial activity related-signaling pathways. ...
Article
The blood-brain barrier (BBB) is a dynamic barrier between the blood microcirculation system and the brain parenchyma, which plays an important role in the pathogenesis of a variety of neurological diseases. Meanwhile, a non-invasive therapeutic approach of photobiomodulation (PBM) has emerged as a promising treatment for neurological disorders through irradiation with near infrared (NIR) light. However, despite multiple encouraging results reported for PBM in vitro and in vivo, the mechanisms of its therapeutic effect on brain, especially on the BBB, remain barely known. Herein, the effect of NIR light irradiation on the in vitro BBB models was studied. 808 nm laser irradiation at the doses of 10 and 30 J/cm2 was found to significantly increase the permeability of this BBB model. The results showed that NIR light affected mitochondria of cells in the in vitro BBB models, leading to an increase in the mitochondrial activity, reactive oxygen species (ROS) level and Ca2+ influx. The activity of matrix metalloproteinases and the expression of the tight junction proteins in the endothelial cells were found to be inhibited by the NIR light, resulting in an increase in the BBB permeability. This study suggested a new strategy for drug transport across the BBB in development of treatments for brain disorders.
... Most studies investigating PBMT for these conditions usually use the transcranial route. 16 The improvement in our patient by previous treatments directed at the scar in the abdominal wall cannot be ruled out. 15 The skin may serve as a neuroendocrine organ and promotes signal exchange with the brain. ...
... 15 The skin may serve as a neuroendocrine organ and promotes signal exchange with the brain. 16 It is possible that specific molecules like nitric oxide (NO) from the body's largest organ (the skin) can be mobilized with potential beneficial effects. 17 The systemic effects of PBMT on mood have been previously reported. ...
Article
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Background This case-report explores the effects of photobiomodulation therapy (PBMT) on the healing of scar tissue. The patient was a 32-year old female two years post cholecystectomy resulting in a 15 cm linear scar that was causing severe pain. Methods Treatment was initiated using the BIOFLEX® therapist device which consists of LED arrays and laser probes of a specific wavelength, power and frequency applied directly on the skin overlying the scar. The frequency and duration of treatment was every other day for six weeks in a clinic setting, followed by three times a week for two months at home. Then the patient continued to use the BIOFLEX® therapist home device on an as-needed basis. Findings The final result of this patient's treatment was significant flattening and decreased redness of her scar. Her self-reported pain decreased to a 6/10. At the one year follow up, the patient reported that she stopped taking her opioids, antidepressant and sleeping pills and that her pain decreased to a 4/10. At the last review her pain score was 1/10; and she had returned to work and took Tylenol (acetaminophen) occasionally for breakthrough pain. Conclusions We attribute the patient's improvement in scar appearance and pain symptoms to PBMT. Since pain is often associated with depressed mood and sleep disturbances, it cannot be determined whether PBMT was the direct or indirect cause of this patient's improved mood. For future studies, we propose the use of control subjects with similar scars treated with sham treatment compared to those who will receive the PBMT and observed for the same duration of time and compare the overall results. Lay Summary Dermatological applications, especially wound healing; are accepted indications for photobiomodulation therapy (PBMT). The expansion into other clinical applications, particularly neurological ones show potential benefit. We present a case of a patient with a hypertrophic scar associated with severe neuropathic pain and concurrent depression, all of which improved directly or indirectly with PBMT. Although the original focus of treatment was dermatological the improvement in pain plus the discontinuation of therapy (opioids, antidepressants and benzodiazepines) were considered to be due to the PBMT.
... Photobiomodulation (PBM) has been used for the treatment of surgical wounds, nerve regeneration, chronic pain, and sports injuries with evidence of its efficacy continuing to accumulate (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). However, the use of PBM for the treatment of snoring and obstructive sleep apnea (OSA) is a relatively recent new development, with the first literature review on PBM and sleep breathing disorders published in 2020 (17). ...
... PBM has been shown to be an effective treatment for certain diseases including inflammatory conditions such as chronic pain, to upregulate the immune system, and to aid in wound closure (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). PBM is now also being used for sleep breathing disorders; specifically for snoring and, more controversially, for OSA (17)(18)(19)(20). ...
... Multiple beneficial effects may be promoted by LLLT, including faster healing of lesions and a reduction in the sensitivity of inflammation and pain in several diseases [13]. The therapeutic effects of LLLT have also been shown in different neurobiological issues such as Alzheimer's disease [14], Parkinson's disease [15], traumatic brain injury [16], and depression [17]. ...
... Studies show that LLLT increases intracellular calcium and DNA synthesis and activates various signaling pathways like anti-apoptotic signaling [18]. Furthermore, LLLT can enhance the immune system and improve neurogenesis, neuroplasticity, and synaptogenesis [17,19]. ...
Article
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Low-level laser therapy (LLLT) and methylene blue (MB) were proved to have neuroprotective effects. In this study, we evaluated the preventive effects of LLLT and MB alone and in combination to examine their efficacy against sleep deprivation (SD)–induced cognitive impairment. Sixty Balb/c male mice were randomly divided into five groups as follows: wide platform (WP), SD, LLLT, MB, LMB (treatment with both LLLT and MB). Daily MB (0.5 mg/kg) was injected for ten consecutive days. An 810-nm, 10-Hz pulsed laser was used in LLLT every other day. We used the T-maze test, social interaction test (SIT), and shuttle box to assess learning and memory and PSD-95, GAP-43, and synaptophysin (SYN) markers to examine synaptic proteins levels in the hippocampus. Our results showed that SD decreased alternation rate in the T-maze test, sociability and social novelty in SIT, and memory index in the shuttle box. Single treatments were not able to reverse these in most of the behavioral parameters. However, behavioral tests showed a significant difference between combined therapy and the SD group. The levels of synaptic plasticity markers were also significantly reduced after SD. There was a significant difference between the MB group and SD animals in GAP-43 and SYN biomarkers. Combination treatment with LLLT and MB also increased GAP-43, PSD-95, and SYN compared to the SD group. We found that the combined use of LLLT and MB pretreatment is more effective in protecting SD-induced cognitive impairment, which may be imparted via modulation of synaptic proteins.
... One of the widely studied and recognized mechanism of action is the stimulation of mitochondria by photons and the consequent increase in intracellular production of adenosine triphosphate (ATP). This contributes to overcome the low ATP level associated with many neurological disorders [6][7][8][9]. Low power tNIR can also increase oxygenation, improve regional circulation and nutritional supplementation to the brain parenchyma by triggering nitric oxide (NO) production, which is an effective vasodilator [10][11][12][13]. ...
Article
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Dementia is a complex syndrome with various presentations depending on the underlying pathologies. Low emission of transcranial near-infrared (tNIR) light can reach human brain parenchyma and be beneficial to a number of neurological and neurodegenerative disorders. We hereby examined the safety and potential therapeutic benefits of tNIR light stimulations in the treatment of dementia. Patients of mild to moderate dementia were randomized into active and sham treatment groups at 2:1 ratio. Active treatment consisted of low power tNIR light stimulations with an active photobiomodulation for 6 min twice daily during 8 consequent weeks. Sham treatment consisted of same treatment routine with a sham device. Neuropsychological battery was obtained before and after treatment. Analysis of variance (ANOVA) was used to analyze outcomes. Sixty subjects were enrolled. Fifty-seven subjects completed the study and had not reported health or adverse side effects during or after the treatment. Three subjects dropped out from trial for health issues unrelated to use of tNIR light treatment. Treatment with active device resulted in improvements of cognitive functions and changes were: an average increase of MMSE by 4.8 points; Logical Memory Tests I and II by ~3.0 points; Trail Making Tests A and B by ~24%; Boston Naming Test by ~9%; improvement of both Auditory Verbal Learning Tests in all subtest categories and overall time of performance. Many patients reported improved sleep after ~7 days of treatment. Caregivers noted that patients had less anxiety, improved mood, energy, and positive daily routine after ~14-21 days of treatment. The tNIR light treatments demonstrated safety and positive cognitive improvements in patients with dementia. Developed treatment protocol can be conveniently used at home. This study suggests that additional dementia treatment trials are warranted with a focus on mitigating caregivers' burden with tNIR light treatment of dementia patients.
... (6) Trail Making Test A & B: in the TMT part A, subjects were instructed to connect randomly positioned circled numbers in their numerical order from 1 to 25. In the TMT Part B, a piece of paper with both circled numbers (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and letters (A-L) was provided to the subject. The subject would connect the circled numbers and letters in order like this: 1-A-2-B until reaching 12-L-13. ...
Article
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Background Transcranial near-infrared (tNIR) stimulation was proven to be a safe, reliable, and effective treatment for cognitive and behavioral symptoms of dementia. Dementia patients of different genders differ in terms of gross anatomy, biochemistry, genetic profile, clinical presentations, and socio-psychological status. Studies of the tNIR effect on dementia have thus far been gender-neutral, with dementia subjects being grouped based on diagnoses or dementia severity. This trial hereby investigated how dementia subjects of different sex respond to tNIR treatment. Methods A total of 60 patient-caregiver dyads were enrolled and randomized to this double-blind, sham-controlled clinical trial. The tNIR light has a wavelength of 1,060 nm to 1,080 nm and was delivered via a photobiomodulation (PBM) unit. The active PBM unit emits near-infrared (NIR) light while the sham unit does not. The treatment consists of a six-minute tNIR light stimulation session twice daily for eight weeks. Neuropsychological assessments conducted at baseline (week 0) and endline (week 8) were compared within the female and male group and between different sex, respectively. Results Over the course of treatment, active-arm female subjects had a 20.2% improvement in Mini-Mental State Exam (MMSE) (mean 4.8 points increase, p < 0.001) and active-arm male cohort had 19.3% improvement (p < 0.001). Control-arm female subjects had a 6.5% improvement in MMSE (mean 1.5 points increase, p < 0.03) and control-arm male subjects had 5.9% improvement (p = 0.35) with no significant differences in the mean MMSE between female and male subjects in both arms respectively. Other comparison of assessments including Clock Copying and Drawing Test, Logical Memory Test - immediate and delayed recall yielded nominal but not statistically significant differences. No significant differences were observed in the mean MMSE between female and male subjects in both arms respectively before treatment implementation (active arm, p = 0.12; control arm, p = 0.50) at week 0, or after treatment completion (active arm, p = 0.11; control arm, p = 0.74) at week 8. Conclusion Despite differences between female and male dementia subjects, the response to tNIR light stimulation does not demonstrate gender-based differences. Further studies are warranted to refine the tNIR treatment protocol for subjects suffering from dementia or dementia-related symptoms.
... 52,53 PBM may stimulate the rich network of neurons comprising the enteric nervous system and directly influence the brain via the vagus nerve to compensate for losses of dopamine, in a mechanism similar to that proposed for transcranial PBM. 52 PBM may also downregulate the systemic inflammation that is a hallmark of many diseases of aging, 54 including PD, 55 via immune cells in abdominal adipose tissue. PBM may directly influence the gut microbiome, as has been recently shown in animal models. ...
Article
Objective: To assess whether remote application of photobiomodulation (PBM) is effective in reducing clinical signs of Parkinson's disease (PD). Background: PD is a progressive neurodegenerative disease for which there is no cure and few treatment options. There is a strong link between the microbiome-gut-brain axis and PD. PBM in animal models can reduce the signs of PD and protect the neurons from damage when applied directly to the head or to remote parts of the body. In a clinical study, PBM has been shown to improve clinical signs of PD for up to 1 year. Methods: Seven participants were treated with PBM to the abdomen and neck three times per week for 12 weeks. Participants were assessed for mobility, balance, cognition, fine motor skill, and sense of smell on enrolment, after 12 weeks of treatment in a clinic and after 33 weeks of home treatment. Results: A number of clinical signs of PD were shown to be improved by remote PBM treatment, including mobility, cognition, dynamic balance, spiral test, and sense of smell. Improvements were individual to the participant. Some improvements were lost for certain participants during at-home treatment, which coincided with a number of enforced coronavirus disease 2019 (COVID-19) pandemic lockdown periods. Conclusions: Remote application of PBM was shown to be an effective treatment for a number of clinical signs of PD, with some being maintained for 45 weeks, despite lockdown restrictions. Improvements in clinical signs were similar to those seen with the application of remote plus transcranial PBM treatment in a previous study. Clinical Trial Registration number: U1111-1205-2035.
... These finding are consistent with our earlier RCT of unilateral tPBM for opioid cravings (49) and with its off-label use in a clinical practice (51) of OUD. We observed no side-effects, and none were reported as is usual in the literature (28,29,64), with one exception, in which a statistically significant, but not clinically significant, 6-point ± SD = 7 increase in diastolic blood pressure was observed over the course of an 8-week tPBM study with an N of 9 in the active group (65), compared with a decrease of 6 points ± 7 in their sham group N = 9. ...
Article
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Background: The opioid epidemic is a global tragedy even with current treatments, and a novel, safe, and effective treatment would be welcomed. We report here our findings from our second randomized controlled trial to evaluate unilateral transcranial photobiomodulation as a treatment for opioid use disorder. Methods: We enrolled 39 participants with active opioid cravings at 2 sites, 19 received the active treatment which consisted of a 4-min twice weekly (every 3 or 4 days) application of a light-emitting diode at 810 nm with an irradiance of 250 mW/cm ² and a fluence of 60 J/cm ² to the forehead over either the left or right dorsolateral prefrontal cortex with a fluence to the brain of 2.1 J/cm ² . Twenty participants received a sham treatment with the same device with foil over the bulb. The side of the treatment was based on Dual-Brain Psychology, which posits that one hemisphere is more affected by past maltreatments and is more prone to anxiety and drug cravings that the other hemisphere. We treated the hemisphere with the more positive hemispheric emotional valence (HEV) by 2 tests for HEV. Results: Our primary outcome was changes in pre-treatment opioid craving scale (OCS) minus baseline, and we found using a mixed model that the active group had a highly significant treatment * time benefit over the sham group, p < 0.0001, effect size at the last follow-up of 1.5. The active treatment benefited those not on buprenorphine as well as those not on it. The TimeLine Follow Back measure of opioid use was significantly better in the actively treated group, p = 0.0001, with an effect size of 0.45. We observed no adverse effects. Conclusion: Active unilateral transcranial photobiomodulation to the brain hemisphere with the better HEV was better than sham in the reduction of opioid cravings and opioid use to a very significant degree in a RCT of 39 participants at 2 independent sites. In the active group those on buprenorphine and those not on it both had improvements in cravings over the study. No adverse responses were reported in either group. ClinicalTrials.gov Identifier: NCT04340622.
... A meta-analysis of articles examining the link between photobiomodulation and biological processes such as metabolism, inflammation, oxidative stress, and neurogenesis suggest these processes are potentially effective targets for photobiomodulation to treat depression and brain injury. It also suggests there is preliminary clinical evidence suggesting the efficacy of photobiomodulation in treating major depressive disorder, comorbid anxiety disorders, and suicidal ideation (Cassano et al., 2016). ...
Conference Paper
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Background: Internalizing disorders (IDs; e.g. posttraumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD)) are the most prevalent form of psychopathology experienced worldwide. Current first-line therapies (e.g. pharmacotherapy) offer high failure rates and substantial side-effects. Closed-loop brain training of electrophysiological signals, also known as electroencephalographic neurofeedback (EEG-NFB), has been shown to be an effective and safe treatment for these conditions, however, there remains much doubt regarding the existence of specificity (i.e. clinical effects specific to the modulation of the EEG variable(s) of interest). This systematic review and meta-analysis was undertaken to determine if there is evidence for EEG-NFB specificity in the treatment of IDs. Methods: We considered all randomised, double-blind, sham/placebo-controlled trials involving humans with at least one ID diagnosis without exclusion by language, locality, ethnicity, age, or sex obtained. We searched various electronic databases and registries including Scopus, PubMed, MEDLINE (Ovid), Cochrane Central Register of Controlled Trials (Ovid), Embase, Allied and Complementary Medicine (Ovid), PsycInfo (Ovid), PsycExtra (Ovid), the World Health Organization's International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and the Australia New Zealand Clinical Trials Registry (ANZCTR). Searches for all databases & registries were last run on 15 May, 2021. Outcomes of interest included self/parent/teacher reports and clinician ratings. Because the included trials utilized different measurement scales to assess clinical outcomes, we utilised standardised mean differences (SMD) and 95% confidence intervals (CIs) calculated from change-from-baseline (CFB) scores. In addition, a sensitivity analysis was performed utilising post-treatment (PI) scores. When appropriate, we contacted trial authors to obtain additional information. A meta-analysis was performed utilizing inverse variance and random effects modelling with results displayed in a forest plot. Additionally, the risk of bias for individual studies was assessed via the RoB 2 (revised Cochrane risk of bias tool for randomised controlled trials) and the certainty of the pooled results was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework. Results: Of 705 unique records identified, 17 full-text reports were evaluated and 4 completed trials (n=152 adult participants) met our criteria, however, only 3 (n=102 adult participants) had publicly available data and were included in our meta-analyses. The overall risk of bias for the individual trials included ranged from ‘some concerns’ to ‘high’. The primary analysis favoured genuine EEG-NFB over sham with a pooled SMD = 0.41 [95% CI 0.01, 0.80]; p = 0.04) with no evidence of heterogeneity (Tau2=0.00, Chi² p=0.96; I² = 0%). Similarly, the sensitivity analysis favoured genuine over sham (SMD = 0.36 [95% CI -0.04, 0.75]; p = 0.07). Per the GRADE, the overall certainty in the evidence was deemed ‘very low’. Discussion: Our primary analysis suggests that EEG-NFB does have specific effects in the treatment of IDs as evidenced by our finding of an overall small mean effect size (0.41). Nonetheless, a mean effect size ranging from nil (0.01) to large (0.80) is also reasonably compatible with the data, given our assumptions. Similar results were evident in our sensitivity analysis. Moreover, the certainty of the pooled results was rated as ‘very low’ due to concerns surrounding reporting biases and imprecision. More randomised, double-blind, sham-controlled trials are needed to verify the existence and, if present, degree of EEG-NFB specificity in the treatment of IDs. Registration: This review was registered on the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42020159702).
... A transcranial device has also been used as a treatment for PD in a series of case studies (28,84) with encouraging results, especially for non-motor symptoms. Evidence from experimental and animal models suggests that transcranial PBM could act via the cytochrome-C-oxidase target of near infrared light, to increase ATP and influence downstream cellular signalling to reduce oxidative stress and neuroinflammation and to upregulate synaptogenesis and neurogenesis (85). ...
Preprint
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BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. OBJECTIVE: To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). METHODS: Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. RESULTS: Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p<0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. CONCLUSIONS: PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted.
... The anti-anxiety effects and the anti-depressive effects of transcranial PBM therapy have been reported. In some studies, an average power density of 1.6 mW/cm 2 can be transmitted through the skin, and skull to reach the cortical surface [89,90]. The best response was found with a laser dose of 8 J/cm 2 in a chronic restraint stress mouse model, which was probably due to increasing 5-HT and decreasing NO levels in the prefrontal cortex and the hippocampal areas [90,91]. ...
Article
Full-text available
Photobiomodulation therapy (PBMT) previously known as low-level laser therapy (LLLT) has been used for over 30 years, to treat neurological diseases. Low-powered lasers are commonly used for clinical applications, although recently LEDs have become popular. Due to the growing application of this type of laser in brain and neural-related diseases, this review focuses on the mechanisms of laser action. The most important points to consider include the photon absorption by intracellular structures; the effect on the oxidative state of cells; and the effect on the expression of proteins involved in oxidative stress, inflammation, pain, and neuronal growth.
... Cerebral PBM [1], a new treatment option, is still under experimental development. However, it has already been used in different approaches like traumatic brain injury (TBI) and stroke [2] or cerebral ischemia [3,4], Alzheimer's disease [5], major depressive disorders [6], cognitive rehabilitation [7], and many other related diseases [8]. ...
Article
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Neuro-photobiomodulation (PBM) is a relatively novel optical stimulation method that is not yet generally accepted in conventional medicine. Therefore, evidence-based research in this sub-area, which is important for laser medicine, is necessary in order to provide appropriate scientific evidence for a better understanding of neuro-PBM. In this editorial, a summary of the recent results with stimulation using different frequencies (e.g., 40 Hz, 136.1 Hz) is presented. The contribution is intended to stimulate researchers to continue working in this promising area of neuro-PBM.
... A transcranial device has also been used as a treatment for PD in a series of case studies [28,84] with encouraging results, especially for nonmotor symptoms. Evidence from experimental and animal models suggests that transcranial PBM could act via the cytochrome-C-oxidase target of near infrared light, to increase ATP and influence downstream cellular signalling to reduce oxidative stress and neuroinflammation and to upregulate synaptogenesis and neurogenesis [85]. ...
Article
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Background: Parkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective: To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods: Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing the same treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results: Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p < 0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions: PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration: Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018.
... There was no difference when the treatment to the two sides was with the placebo treatment. In both RCTs we had no side-effects at all, and in the extensive literature there have been no significant adverse reactions [23,24]. ...
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In this paper I will address questions about will, agency, choice, consciousness, relevant brain regions, impacts of disorders, and their therapeutics, and I will do this by referring to my theory, Dual-brain Psychology, which posits that within most of us there exist two mental agencies with different experiences, wills, choices, and behaviors. Each of these agencies is associated as a trait with one brain hemisphere (either left or right) and its composite regions. One of these agencies is more adversely affected by past traumas, and is more immature and more symptomatic, while the other is more mature and healthier. The theory has extensive experimental support through 17 peer-reviewed publications with clinical and non-clinical research. I will discuss how this theory relates to the questions about the nature of agency and I will also discuss my published theory on the physical nature of subjective experience and its relation to the brain, and how that theory interacts with Dual-Brain Psychology, leading to further insights into our human nature and its betterment.
... Although the current experimental data show that transcranial PBM is safe and well tolerated, and there are no documents incidents of retinal or skin injury in patients treated with PBM, we should also pay attention to it. Given the potential risk of injury when high-powered NIR devices are used by untrained personnel or laypersons, over-the-counter availability is not recommended for devices with high transmitting power (>1 W) (Cassano et al., 2016;Kim et al., 2007). ...
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Alzheimer's disease (AD), a severe age‐related neurodegenerative disorder, lacks effective therapeutic methods at present. Physical approaches such as gamma frequency light flicker that can effectively reduce amyloid load have been reported recently. Our previous research showed that a physical method named photobiomodulation (PBM) therapy rescues Aβ‐induced dendritic atrophy in vitro. However, it remains to be further investigated the mechanism by which PBM affects AD‐related multiple pathological features to improve learning and memory deficits. Here, we found that PBM attenuated Aβ‐induced synaptic dysfunction and neuronal death through MKP7‐dependent suppression of JNK3, a brain‐specific JNK isoform related to neurodegeneration. The results showed PBM‐attenuated amyloid load, AMPA receptor endocytosis, dendrite injury, and inflammatory responses, thereby rescuing memory deficits in APP/PS1 mice. We noted JNK3 phosphorylation was dramatically decreased after PBM treatment in vivo and in vitro. Mechanistically, PBM activated ERK, which subsequently phosphorylated and stabilized MKP7, resulting in JNK3 inactivation. Furthermore, activation of ERK/MKP7 signaling by PBM increased the level of AMPA receptor subunit GluR 1 phosphorylation and attenuated AMPA receptor endocytosis in an AD pathological model. Collectively, these data demonstrated that PBM has potential therapeutic value in reducing multiple pathological features associated with AD, which is achieved by regulating JNK3, thus providing a noninvasive, and drug‐free therapeutic strategy to impede AD progression.
... There is a brief increase in ROS generated in the mitochondria when they absorb the photons delivered during PBMT treatment, and this burst of ROS will trigger some mitochondrial signaling pathways leading to cytoprotective, antioxidant, and antiapoptotic effects in the cells [69,74]. In terms of antioxidation, there are multiple antioxidant enzymes in cell function to scavenge and degrade ROS in different subcellular compartments to allow the development and persistence of oxidative signals [75,76]. Moreover, the antioxidant system helps regulate ROS signaling by limiting the extent of protein oxidation in both spatial and time [75]. ...
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Background Adult hippocampal neurogenesis (AHN) is restricted under the pathological conditions of neurodegenerative diseases, especially in Alzheimer’s disease (AD). The drop of AHN reduces neural circuit plasticity, resulting in the decrease of the generation of newborn neurons in dentate gyrus (DG), which makes it difficult to recover from learning/memory dysfunction in AD, therefore, it is imperative to find a therapeutic strategy to promote neurogenesis and clarify its underlying mechanism involved. Methods Amyloid precursor protein/presenilin 1 (APP/PS1) mice were treated with photobiomodulation therapy (PBMT) for 0.1 mW/mm ² per day in the dark for 1 month (10 min for each day). The neural stem cells (NSCs) were isolated from hippocampus of APP/PS1 transgenic mice at E14, and the cells were treated with PBMT for 0.667 mW/mm ² in the dark (5 min for each time). Results In this study, photobiomodulation therapy (PBMT) is found to promote AHN in APP/PS1 mice. The latent transforming growth factor-β1 (LTGFβ1) was activated in vitro and in vivo during PBMT-induced AHN, which promoted the differentiation of hippocampal APP/PS1 NSCs into newborn neurons. In particular, behavioral experiments showed that PBMT enhanced the spatial learning/memory ability of APP/PS1 mice. Mechanistically, PBMT-stimulated reactive oxygen species (ROS) activates TGFβ/Smad signaling pathway to increase the interaction of the transcription factors Smad2/3 with Smad4 and competitively reduce the association of Smad1/5/9 with Smad4, thereby significantly upregulating the expression of doublecortin (Dcx)/neuronal class-III β-tubulin (Tuj1) and downregulating the expression of glial fibrillary acidic protein (GFAP). These in vitro effects were abrogated when eliminating ROS. Furthermore, specific inhibition of TGFβ receptor I (TGFβR I) attenuates the DNA-binding efficiency of Smad2/3 to the Dcx promotor triggered by PBMT. Conclusion Our study demonstrates that PBMT, as a viable therapeutic strategy, directs the adult hippocampal APP/PS1 NSCs differentiate towards neurons, which has great potential value for ameliorating the drop of AHN in Alzheimer’s disease mice.
... 90 In the modern day, this is otherwise known as brain photobiomodulation therapy and has been used in the management of various neuropsychiatric conditions. 91,92 The antidepressant effect of light therapy lies in its effect on the retino-geniculo-habenular pathway, circuitry likely involved in depression and other mood disorders. 93 At the molecular level, light therapy stimulates ATP synthesis via the mitochondrial respiratory chain and activates various pathways leading to neuronal and synaptic regeneration. ...
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Stroke is a major cause of death and disability globally. Post-stroke depression (PSD) is a major driver for poor recovery and poor quality of life with extra burden for the patient and the caregiver. We have previously shown the inflammatory basis of PSD with associated bioenergetic failure, disruption of the blood-brain barrier, cell death, and persistent maladapted inflammation, making the PSD a norm rather than the exception, highlighting the unmet need for therapeutic intervention in PSD across the recovery trajectory. In this era, various interventions are focused on pharmacotherapy; however, non-pill-based medication should also be explored as post-stroke patients are likely to suffer from the adverse effects of polypharmacy. This narrated review explores the status of non-pharmacological interventions in managing PSD. We performed a PubMed search using pre-specified keywords looking at various non-pharmacologic approaches for the management of PSD. Worldwide, approaches such as non-invasive brain stimulation, behavioral and psychosocial therapy, as well as exercise, acupuncture, music, literature, and art therapies are available as monotherapy or adjunctive treatment for PSD. While current literature shows convincing results on the benefits of non-pharmacologic interventions, more robust studies are necessary to determine its utility in PSD.
... A great amount of research into photobiomodulation has been accumulated over decades and published in 2,240 PubMed citations. Reviews of this literature emphasize that biophotomodulation increases blood flow, ATP production, brain neurotropic factors, and decreases inflammation (Cassano et al., 2016;Hamblin, 2016), but none of these facts explain the rapid onset of our UtPBM treatment effects. I have suggested that the LED-emitted transcranial photons may have quantum effects related to endogenous biophoton stimulation and interactions with a hypothesized fundamental quantum subjective field (Schiffer, 2019(Schiffer, , 2021a, but this hypothesis has not yet been testable. ...
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Dual-Brain Psychology is a theory and its clinical applications that come out of the author's clinical observations and from the Split-brain Studies. The theory posits, based on decades of rigorous, peer-reviewed experiments and clinical reports, that, in most patients, one brain's cerebral hemisphere (either left or right) when stimulated by simple lateral visual field stimulation, or unilateral transcranial photobiomodulation, reveals a dramatic change in personality such that stimulating one hemisphere evokes, as a trait, a personality that is more childlike and more presently affected by childhood maltreatments that are usually not presently appreciated but are the proximal cause of the patient's symptoms. The personality associated with the other hemisphere is much more mature, less affected by the traumas, and less symptomatic. The theory can be applied to in-depth psychotherapy in which the focus is on helping the troubled side to bear and process the traumas with the help of the therapist and the healthier personality. A person's symptoms can be evoked to aid the psychotherapy with hemispheric stimulation and the relationship between the dual personalities can be transformed from conflicted and sabotaging to cooperating toward overall health. Stimulating the positive hemisphere in most therapy patients rapidly relieves symptoms such as anxiety, depression, or substance cravings. Two randomized controlled trials used unilateral transcranial photobiomodulation to the positive hemisphere as a stand-alone treatment for opioid cravings and both revealed high effect sizes. The theory is supported by brain imaging and rTMS studies. It is the first psychological theory and application that comes out of and is supported by rigorous peer-reviewed experimentation.
... The light that penetrates cerebral tissue is absorbed by cytochrome c oxidase (CCO) in the mitochondrial electron transport chain, which leads to enhancement of mitochondrial redox metabolism 1,2,5 and increased production of adenosine triphosphate and ultimately benefits brain functions. [6][7][8] Recent studies have shown that a few minutes of tPBM over the frontal cortex could significantly improve cognitive outcomes, such as memory 7 and executive function 9 in young adults. Meanwhile, other studies have also documented the beneficial effects of repeated tPBM treatment on improving the cognitive capacity of patients with mental or neurological disorders. ...
Article
Significance: Decline in cognitive ability is a significant issue associated with healthy aging. Transcranial photobiomodulation (tPBM) is an emerging non-invasive neuromodulation technique and has shown promise to overcome this challenge. Aim: This study aimed to investigate the effects of seven-day repeated tPBM, compared to those of single tPBM and baseline, on improving N -back working memory in healthy older adults and to evaluate the persistent efficacy of repeated tPBM. Approach: In a sham-controlled and within-subject design, 61 healthy older adults were recruited to participate in a longitudinal study involving an experimental baseline, seven days of tPBM treatment (12 min daily, 1064-nm laser, 250 mW / cm 2 ) in the left dorsolateral prefrontal cortex and three weeks of follow-ups. Behavioral performance in the N -back ( N = 1,2 , 3 ) was recorded poststimulation during the baseline, the first and seventh days of the tPBM session, and the three weekly follow-ups. A control group with 25 participants was included in this study to rule out the practice and placebo effects. The accuracy rate and response time were used in the statistical analysis. Results: Repeated and single tPBM significantly improved accuracy rate in 1- and 3-back tasks and decreased response time in 3-back compared to the baseline. Moreover, the repeated tPBM resulted in a significantly higher improvement in accuracy rate than the single tPBM. These improvements in accuracy rate and response time lasted at least three weeks following repeated tPBM. In contrast, the control group showed no significant improvement in behavioral performance. Conclusions: This study demonstrated that seven-day repeated tPBM improved the working memory of healthy older adults more efficiently, with the beneficial effect lasting at least three weeks. These findings provide fundamental evidence that repeated tPBM may be a potential intervention for older individuals with memory decline.
... Compared with the traditional therapeutic method, PBM therapy shows unparalleled advantages in noninvasiveness, which gives a broad prospect in the promotion of clinical application, such as traumatic brain injury, stroke, and depression [40,41]. Recent studies have demonstrated that PBM could exert a prominent effect on inhibiting neuroinflammation via reducing proinflammatory factors and promoting M2 microglia polarization [42,43] and that it could increase neurogenesis via elevating neurotrophic factors, such as BDNF [44]. Meanwhile, recent studies have demonstrated that the elevation of BDNF could also exert an anti-inflammatory effect as we have mentioned above. ...
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Background: Neuroinflammation plays a key role in myocardial ischemia-reperfusion (I/R) injury. Previous studies showed that light-emitting diode (LED) therapy might improve M2 microglia activation and brain-derived neurotrophic factor (BDNF) expression, thereby exerting anti-inflammatory effects. Therefore, we hypothesized that LED therapy might reduce myocardial I/R injury by neuroinflammation modulation. Objective: To explore the effect of LED therapy on myocardial I/R-induced injury and seek the underlying mechanism. Methods: Thirty rats were randomly divided into three groups: Control group (without LED treatment or myocardial I/R, n = 6), I/R group (with myocardial I/R only, n = 12), and LED+I/R group (with myocardial I/R and LED therapy, n = 12). Electrocardiogram was recorded continuously during the procedure. In addition, brain tissue was extracted for BDNF, Iba1, and CD206 analyses, and heart tissue for myocardial injury (ischemic size and infarct size), IL-4 and IL-10 mRNA analysis. Results: In comparison with the I/R group, the ischemia size and the infarct size were significantly attenuated by LED therapy in the LED+I/R group. Meanwhile, the microglia activation induced by I/R injury was prominently attenuated by LED treatment either. And it is apparent that there was also an increase in the beneficial neuroinflammation markers (BDNF and CD206) in the paraventricular nucleus (PVN) in the LED+I/R group. Furthermore, the anti-inflammatory cytokines, IL-4 and IL-10, were greatly decreased by I/R while improved by LED treatment in myocardium. Conclusion: LED therapy might reduce neuroinflammation in PVN and decrease myocardium injury by elevating BDNF and M2 microglia.
... Although the effect of infrared light on weight loss is controversial (Montazeri et al., 2017), the application of light through cranial manipulations, has shown to improve cognitive deficits related to mood and memory (Cassano et al., 2016). Photobiomodulation is said to involve the activation of the mitochondria (Hamblin, 2018), and since neurons contain abundant mitochondria, and because several neurological diseases are characterised by mitochondrial dysfunction, this treatment may prove to be useful. ...
Article
Obesity and anxiety are public health problems that have no effective cure. Obesity-induced anxiety is also the most common behavioural trait exhibited amongst obese patients, with the mechanisms linking these disorders being poorly understood. The hypothalamus and hippocampus are reciprocally connected, important neurogenic brain regions that could be vital to understanding these disorders. Dietary, physical activity and lifestyle interventions have been shown to be able to enhance neurogenesis within the hippocampus, while the effects thereof within the hypothalamus is yet to be ascertained. This review describes hypothalamic neurogenesis, its impairment in obesity as well as the effect of interventional therapies. Obesity is characterized by a neurogenic shift towards neuropeptide Y neurons, promoting appetite and weight gain. While, nutraceuticals and exercise promote proopiomelanocortin neuron proliferation, causing diminished appetite and reduced weight gain. Through the furthered development of multimodal approaches targeting both these brain regions could hold an even greater therapeutic potential.
... Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light may be a promising treatment option for various psychiatric and neurological conditions [14][15][16][17]. Cadaver studies have shown that NIR can penetrate the skull and soft tissues of the forehead to affect brain cortical areas (10)(11)(12). ...
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Introduction: Mood and anxiety disorders are a prevalent and significant leading cause of years lived with a disability worldwide. Existing antidepressants drugs are only partially effective, having burdensome side effects. One-third of patients do not achieve remission after several adequate antidepressant trials, and relapses of depression are frequent. Psychotherapies for depression are limited by the lack of trained professionals, and further by out-of-pocket prohibitive costs. Existing FDA-approved, device-based interventions are either invasive or only administered in the office. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light may be a promising treatment option for mood and anxiety disorders. Due to its low cost, and ease of self-administration, t-PBM has the potential to become widely accessible. The safety profile of t-PBM is a relevant factor for widespread use and administration. Aim: To further investigate the t-PBM safety profile, this study aims to evaluate the tolerability and safety of t-PBM for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Method: We completed a systematic analysis of the side effects from repeated sessions of t-PBM in three studies: an open-label study for GAD (LIGHTEN GAD) and two randomized control studies for MDD (ELATED-2; ELATED-3). Overall, 80 subjects were studied. Result: Our results show that a low dose of NIR per t-PBM session can be administered with increasing frequency (up to daily sessions) and for several weeks (up to 12 weeks) without a corresponding increase in the occurrence or severity of adverse events. Additionally, there were no significant predictors for the variance in the number of reported adverse events (such as age, sex or diagnosis). Conclusion: The literature indicates that higher dosages of transcranial NIR could lead to greater antidepressant and anxiolytic effects; this study did not find any correlation between the increasing number of t-PBM sessions and the occurrence of adverse events
... 1 However, the main challenge of using lowenergy NIR photons is the high degree of complex interactions with human tissues due to the presence of high scattering, which is much greater than that of x-rays. As a result, the success of many emerging NIR-based imaging or intervention techniques, such as diffuse optical tomography, 2 functional near-infrared spectroscopy, 3 photobiomodulation, 4 etc., requires a quantitative understanding of such complex photon-tissue interactions via computation-based models. ...
Article
Significance: The Monte Carlo (MC) method is widely used as the gold-standard for modeling light propagation inside turbid media, such as human tissues, but combating its inherent stochastic noise requires one to simulate a large number photons, resulting in high computational burdens. Aim: We aim to develop an effective image denoising technique using deep learning (DL) to dramatically improve the low-photon MC simulation result quality, equivalently bringing further acceleration to the MC method. Approach: We developed a cascade-network combining DnCNN with UNet, while extending a range of established image denoising neural-network architectures, including DnCNN, UNet, DRUNet, and deep residual-learning for denoising MC renderings (ResMCNet), in handling three-dimensional MC data and compared their performances against model-based denoising algorithms. We also developed a simple yet effective approach to creating synthetic datasets that can be used to train DL-based MC denoisers. Results: Overall, DL-based image denoising algorithms exhibit significantly higher image quality improvements over traditional model-based denoising algorithms. Among the tested DL denoisers, our cascade network yields a 14 to 19 dB improvement in signal-to-noise ratio, which is equivalent to simulating 25 × to 78 × more photons. Other DL-based methods yielded similar results, with our method performing noticeably better with low-photon inputs and ResMCNet along with DRUNet performing better with high-photon inputs. Our cascade network achieved the highest quality when denoising complex domains, including brain and mouse atlases. Conclusions: Incorporating state-of-the-art DL denoising techniques can equivalently reduce the computation time of MC simulations by one to two orders of magnitude. Our open-source MC denoising codes and data can be freely accessed at http://mcx.space/.
... Neuromodulation of the brain using transcranial and intranasal PBM has been shown to improve cerebral hemodynamics along with an increase in cerebral oxygenation and metabolic capacity [3,4]. Additionally, there is a rapidly increasing body of evidence to support that PBM therapy of the brain can ameliorate neuronal oxidative stress, neuroinflammation, and apoptosis, while promoting neurogenesis and synaptogenesis [5,6]. To date, no serious adverse effects have been reported in the literature for brain PBM therapy; however, caution must be considered with high-power laser sources 2 of 18 (class 3B and 4) due to the hazard for macular lesions [7]. ...
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The glymphatic system is a glial-dependent waste clearance pathway in the central nervous system, devoted to drain away waste metabolic products and soluble proteins such as amyloid-beta. An impaired brain glymphatic system can increase the incidence of neurovascular, neuroinflammatory, and neurodegenerative diseases. Photobiomodulation (PBM) therapy can serve as a non-invasive neuroprotective strategy for maintaining and optimizing effective brain waste clearance. In this review, we discuss the crucial role of the glymphatic drainage system in removing toxins and waste metabolites from the brain. We review recent animal research on the neurotherapeutic benefits of PBM therapy on glymphatic drainage and clearance. We also highlight cellular mechanisms of PBM on the cerebral glymphatic system. Animal research has shed light on the beneficial effects of PBM on the cerebral drainage system through the clearance of amyloid-beta via meningeal lymphatic vessels. Finally, PBM-mediated increase in the blood–brain barrier permeability with a subsequent rise in Aβ clearance from PBM-induced relaxation of lymphatic vessels via a vasodilation process will be discussed. We conclude that PBM promotion of cranial and extracranial lymphatic system function might be a promising strategy for the treatment of brain diseases associated with cerebrospinal fluid outflow abnormality.
... Likewise, it has been shown to be effective in the treatment of traumatic brain injury and neurodegenerative diseases (Hamblin, 2018b;Oron and Oron, 2016;Salehpour and Hamblin, 2020). In the psychological realm, it has displayed effects on learning and memory, attention, executive functions, and several psychiatric disorders (Cassano et al., 2016). Therefore, PBM can be considered an innovative and potential treatment for a wide range of neurological, psychological, and psychiatric disorders (Salehpour et al., 2018b) from a non-invasive, inexpensive, and safe perspective (Rojas and Gonzalez-Lima, 2013). ...
Article
Photobiomodulation is a brain modulation technique that has become a promising treatment for multiple pathologies. This systematic review collects studies up to 2019 about the beneficial effects of photobiomodulation as a therapy for treating psychological disorders and a tool for modulating cognitive processes. This technique is mostly used for the treatment of depression and stress, as well as to study its effects on psychological variables in healthy subjects. Despite the lack of parameters used, photobiomodulation seems to achieve enough brain penetration to produce beneficial effects in healthy subjects and patients with multiple pathologies. The best parameters are the wavelengths of 810 nm for the treatment of depression and 1064 nm for cognitive enhancement, along with a scalp irradiance of 250 mW/cm² and a scalp yield of 60 J/cm². It weekly application on the bilateral prefrontal area and the default mode network seems to be ideal for the maintenance of the effects. Photobiomodulation could be used as an effective and safe therapy for the treatment of multiple psychological pathologies.
... However, the precise mechanism(s) of PBM modulation for the treatment of AD remain elusive [20]. Traumatic brain injury, stroke, neurodegenerative diseases (AD and Parkinson's), and psychiatric disorders (depression, anxiety, insomnia, post-traumatic stress disorder (PTSD)) all respond well to PBM [20][21][22][23]. Therefore, using a novel AD-like transgenic rat model, the TgF344-AD rat, the current study was designed to investigate the effects and underlying mechanism(s) of long-term PBM initiated at the early stages of AD. ...
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Alzheimer's disease (AD) is the most common form of dementia in the elderly, causing neuronal degeneration and cognitive deficits that significantly impair independence and quality of life for those affected and their families. Though AD is a major neurodegenerative disease with vast avenues of investigation, there is no effective treatment to cure AD or slow disease progression. The present work evaluated the therapeutic effect of long-term photobiomodulation (PBM) treatment with continuous-wave low-level laser on AD and its underlying mechanism. Methods: PBM was implemented for 2 min, 3 times per week for 16 months in 2-month-old transgenic AD rats. A battery of behavioral tests was performed to measure the effect of PBM treatment on cognitive dysfunction in AD rats. The effects of PBM therapy on typical AD pathologies, including amyloid plaques, intracellular neurofibrillary tangles, neuronal loss, neuronal injury, neuronal apoptosis, and neurodegeneration, were then assessed. The underlying mechanisms were measured using immunofluorescence staining, western blotting analysis, mass spectrometry, primary cortical and hippocampal cell cultures, and related assay kits. Results: PBM treatment significantly improved the typical AD pathologies of memory loss, amyloid plaques, tau hyperphosphorylation, neuronal degeneration, spine damage, and synaptic loss. PBM treatment had several mechanistic effects which may explain these beneficial effects, including 1) regulation of glial cell polarization and inhibition of neuroinflammation, 2) preservation of mitochondrial dynamics by regulating fission and fusion proteins, and 3) suppression of oxidative damage to DNA, proteins, and lipids. Furthermore, PBM enhanced recruitment of microglia surrounding amyloid plaques by improving the expression of microglial IL-3Rα and astrocytic IL-3, which implies a potential role of PBM in improving Aβ clearance. Finally, our results implicate neuronal hemoglobin in mediating the neuroprotective effect of PBM, as Hbα knockdown abolished the neuroprotective effect of PBM treatment. Conclusion: Collectively, our data supports the potential use of PBM treatment to prevent or slow the progression of AD and provides new insights into the molecular mechanisms of PBM therapy.
... Photobiomodulation means a use of light in selected wavelengths for purposes of healing tissues, enhancing a recovery speed, alleviating pain, or restoring function [110][111][112][113]. Among several types of photobiomodulation, a method of irradiating light to the brain for performing functions of treatments, recovery and symptom mitigation is called transcranial photobiomodulation [114][115][116][117][118], and light with spectral bands of red or infrared is generally employed in this process due to its relatively high penetration efficiency. Several research groups have studied transcranial photobiomodulation for brain diseases in three categories: stroke/ischemia, degenerative diseases (such as Alzheimer's disease), and psychiatric diseases (for instance, bipolar disorder). ...
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Stroke is the second most common cause of death and third most common cause of disability worldwide. Therefore, it is an important disease from a medical standpoint. For this reason, various studies have developed diagnostic and therapeutic techniques for stroke. Among them, developments and applications of optical modalities are being extensively studied. In this article, we explored three important optical modalities for research, diagnostic, and therapeutics for stroke and the brain injuries related to it: (1) photochemical thrombosis to investigate stroke animal models; (2) optical imaging techniques for in vivo preclinical studies on stroke; and (3) optical neurostimulation based therapy for stroke. We believe that an exploration and an analysis of previous studies will help us proceed from research to clinical applications of optical modalities for research, diagnosis, and treatment of stroke.
... The primary PBM targets are linked to the endogenous release of reactive oxygen species (ROS) and NO, ATP production, and modulation of Ca 2+ fluxes and redox homeostasis, which can play a key role in cell proliferation, growth, and apoptosis [66][67][68]. Therefore, PBM therapy seems to support treatments in many medical and veterinary areas to restore cell dysfunction and promote recovery from illness [62,[69][70][71][72][73][74][75]. PBM therapy has been recommended unequivocally for oral mucositis prevention in patients treated with chemotherapy by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology [76]. ...
Article
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Photobiomodulation (PBM) consists of a photon energy transfer to the cell, employing non-ionizing light sources belonging to the visible and infrared spectrum. PBM acts on some intrinsic properties of molecules, energizing them through specific light wavelengths. During the evolution of life, semiconducting minerals were energized by sun radiation. The molecules that followed became photoacceptors and were expressed into the first proto-cells and prokaryote membranes. Afterward, the components of the mitochondria electron transport chain influenced the eukaryotic cell physiology. Therefore, although many organisms have not utilized light as an energy source, many of the molecules involved in their physiology have retained their primordial photoacceptive properties. Thus, in this review, we discuss how PBM can affect the oral microbiota through photo-energization and the non-thermal effect of light on photoacceptors (i.e., cytochromes, flavins, and iron-proteins). Sometimes, the interaction of photons with pigments of an endogenous nature is followed by thermal or photodynamic-like effects. However, the preliminary data do not allow determining reliable therapies but stress the need for further knowledge on light-bacteria interactions and microbiota management in the health and illness of patients through PBM.
... Moreover, light induces a complex chain of physiological reactions in tissues through its photophysical and photochemical effects, which in turn helps to restore normal cellular functions by promoting blood circulation and reducing inflammation [1] by way of distinct photoreceptors in the retina such as melanopsin or neuropsin expressed in retinal ganglion cells other than the traditional rods and cones [2]. As such, photobiological neuromodulation therapy for brain has potential to enhance the metabolic capacity of neurons and stimulate anti-inflammatory, anti-apoptotic, and antioxidant responses, neurogenesis, and synapse formation, and thus it is expected to have therapeutic applications for central nervous system diseases including depression and dementia [3]. ...
Article
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Photobiological neuromodulation and its clinical application has been investigated in recent years. The response of the gamma-oscillation to human visual stimuli is known to be both burst and resonant in nature, and the coupling between alpha and gamma oscillations may play a functional role in visual processing. To date, there is no study that examined the effects of gamma-frequency violet light (VL) stimulation on human electroencephalography (EEG). In this study, we investigated the neurophysiological changes induced by light stimulation using EEG. The purpose of this study was to evaluate the specific effects of 40 Hz gamma-frequency VL stimulation on EEG activity by comparing the effects of white light (WL) with the same condition. Twenty healthy participants (10 females: 37.5 ± 14.3 years; 10 males: 38.0 ± 13.3 years) participated in this study and the following results were observed. First, when compared with the power spectrum density (PSD) of baseline EEG, 40 Hz-WL induced significant increase of PSD in theta band. Second, compared the PSDs between EEG with 40 Hz-VL and EEG with 40 Hz-WL, 40 Hz-VL induced significantly lower enhancement in delta and theta bands than 40 Hz-WL. Third, when focused on the occipital area, negative peak of VEP with 40 Hz-VL was smaller than that of 40 Hz-WL. Fourth, 40 Hz-VL induced an increase of alpha-gamma coupling during the VEP at the F5 electrode site as well as post-EEG at the C4 electrode site, compared with baseline EEG. Thus, the present study suggested that 40 Hz-VL stimulation may induce unique photobiological neuromodulations on human EEG activity.
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Introduction Opioid Use Disorders (OUD) cause great disfunction and pain to individuals, families, and societies. There are few good treatments. This paper presents a novel, easily applied, painless, therapy that can be applied as an adjunct to psychotherapies and medications. Methods The author presents a retrospective overview and 4 brief case reports. Two are typical of very positively responsive patients, one is of a positively but not remarkably responsive patient, and one of a non-responsive patient. The author used unilateral transcranial photobiomodulation (UtPBM), near infrared mode, applied to the hemisphere with the more positive hemispheric emotional valence (HEV) as a treatment to augment the patients’ usual treatment. Results: The case reports are from 42 consecutive patients in his practice with OUD where he has given 382 treatments over 18 months, as needed. The author’s subjective clinical observations were that of the 42 patients, 26 (62%) consistently had responses to the UtPBM (as described in the case reports) that were easily observable to the patient and the author as strikingly beneficial, 8 (19%) had helpful, but not remarkable responses, and 8 (19%) had no noticeable response. These 3 characterizations will be illustrated with clinical examples. There were no side-effects reported or observed aside from 2 women who experienced anxiety which resolved with psychotherapy. Conclusions Using UtPBM as an adjunctive treatment to the author’s usual in-depth psychotherapy and medication management, he found subjectively that for the majority of his patients, this treatment was a valuable, safe benefit to their treatment for OUD.
Article
Objective: The objective of this narrative review was to investigate the history of light therapy in hospital settings, with reference to physiotherapy and particularly in an Australian context.Types of articles and search method:a review of available literature was conducted on PubMed, Medline and Google Scholar using keywords light therapy, photobiomodulation, physiotherapy, low-level laser, heliotherapy. Physiotherapy textbooks from Sydney University Library were searched. Historical records were accessed from the San Hospital library. Interviews were conducted with the San Hospital Chief Librarian and a retired former Head Physiotherapist from Royal Prince Alfred Hospital.Summary: Historically, light treatment has been used in both medical and physiotherapy practice. From its roots in ancient Egypt, India, and Greece, through to medieval times, the modern renaissance in ‘light as therapy ’ was begun by Florence Nightingale who, in the 1850s, advocated the use of clean air and an abundance of sunlight to restore health. Modern light therapy (phototherapy) had a marked uptake in use in medicine in Scandinavia, America, and Australia from 1903, following the pioneering work of Niels Finsen in the late 19th century, which culminated in Dr Finsen receiving the Nobel Prize for Medicine for the treatment of tuberculosis scarring with ultraviolet (UV) light, and treatment of smallpox scarring with red light. Treatment with light, especially UVB light, has been widely applied by physiotherapists in hospitals for dermatological conditions since the 1950s, particularly in Australia, Scandinavia, USA, England and Canada. In parallel, light treatment in hospitals for hyperbilirubinemia was used for neonatal jaundice. Since the 1980s light was also used in the medical specialties of ophthalmology, dermatology, and cardiology. In more recent years in physiotherapy, light was mostly used as an adjunct to the management of orthopedic/rheumatological conditions. Since the 1990s, there has been global use of light, in the form of photobiomodulation for the management of lymphedema, including in supportive cancer care. Photobiomodulation in the form of low-level laser has been used by physiotherapists and pain doctors since the 1990s in the management of chronic pain. The use of light as therapy is exemplified by its use in the San Hospital in Sydney, where light therapy was introduced in 1903 (after Dr. John Harvey Kellogg visited Niels Finsen in Denmark) and is practiced by nurses, physiotherapists and doctors until the present day. The use of light has expanded into new and exciting practices including supportive cancer care, and treatment of depression, oral mucositis, retinopathy of prematurity, and cardiac surgery complications. Light is also being used in the treatment of neurological diseases, such as Parkinson‘s disease, traumatic brain injury, and multiple sclerosis. The innovative uses of light in physiotherapy treatment would not be possible without the previous experience of successful application of light treatment.Conclusion: Light therapy has had a long tradition in medicine and physiotherapy. Although it has fallen somewhat out of favour over the past decades, there has been a renewed interest using modern techniques in recent times. There has been continuous use of light as a therapy in hospitals in Australia, most particularly the San Hospital in Sydney where it has been in use for almost 120 years.
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Post-stroke depression is associated with both significantly increased post-stroke morbidity and mortality. Depression persists after 20 months in 34% of elderly patients with acute stroke and has been linked to both worse cognitive and physical outcomes. The development of animal models and the start of the genome-wide era and the recent progress made in the genetics field have given an approach to find biomarkers and potential drug targets related to post-stroke outcomes. Recent clinical findings have demonstrated that subacute antidepressant treatment or transcranial magnetic stimulation or photobiomodulation after stroke may exert beneficial effects on various aspects of stroke outcome extending beyond mood effects. Successful management of stroke sequelae should include cognitive assessment in the short and long term, and great efforts should be oriented toward a multidisciplinary approach, including quality-of-life assessment and support of caregivers.
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A positive effect of photoneuromodulation (PNM) has been found on cognitive and emotional functions in healthy populations. However, the hemodynamic changes associated with improved cognitive functions (i.e., memory and executive functions) are unexplored. Therefore, the present study investigated the hemodynamic changes associated with PNM using functional near-infrared spectroscopy (fNIRS). In this experiment, 33 young healthy adults were recruited and randomly assigned to control and experimental groups. A single PNM stimulation was applied to the forehead in the experimental group, while a sham stimulation (same procedure without machine activation) was performed for the control group. Before and after the stimulation, all participants performed an n-back task with 0-and 3-back conditions to assess their working memory function, and their hemodynamic responses during the tasks were measured by fNIRS. A significant group (experimental vs. control) × time (before vs. after PNM) interaction in memory-related frontal activation was found. Specifically, only the experimental group had a significant reduction in frontal hemodynamic levels during the difficult task. Additionally, the memory-related frontal activation was significantly correlated with the immediate and delayed recall of the Rey–Osterrieth Complex Figure Test assessed at baseline. Therefore, PNM may reduce the cognitive efforts needed to complete tasks with high memory loads.
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Longevity is one of the great triumphs of humanity. Worldwide, the elderly is the fastest growing segment of the population. As a consequence, the number of cases of age-related cognitive decline and neurological diseases associated with aging, such as Alzheimer's and Parkinson's, has been increasing. Among the non-pharmacological interventions studied for the treatment or prevention of age-related neurocognitive impairment, photobiomodulation (PBM) has gained prominence for its beneficial effects on brain functions relevant to aging brains. In animal models, the neuroprotective and neuromodulatory capacity of PBM has been observed. Studies using both animals and humans have shown promising metabolic and hemodynamic effects of PBM on the brain, such as improved mitochondrial and vascular functions. Studies in humans have shown that PBM can improve electrophysiological activity and cognitive functions such as attention, learning, memory and mood in older people. In this paper we will review the main brain effects of PBM during aging, discuss its mechanisms of action relevant to the aging brain, and call for more controlled studies in older populations.
Article
Background: Major depressive disorder (MDD) is prevalent and has significant impact on individuals and society. Cognitive symptoms are frequent in MDD and insufficiently treated by antidepressant medications. Transcranial photobiomodulation (t-PBM) is a novel device therapy which shows promise as an antidepressant and pro-cognitive treatment. To date, despite the encouraging results, the optimal stimulation parameters of t-PBM to treat MDD are not established, and clinical studies are very heterogeneous in terms of these parameters. While the literature provides guidance on the appropriate fluence to achieve therapeutic results, little is known on the other parameters. Objective: To evaluate the relationship between different parameters and the antidepressant effect of t-PBM. Methods: We reviewed clinical studies on MDD and on depressive symptoms comorbid with other diseases. We calculated the standardized effect size of the change in symptoms severity before and after t-PBM and we performed a descriptive analysis of the reviewed papers. Results: The greatest effect sizes for the antidepressant effect were found in studies using pulse-wave t-PBM with high peak irradiance (but low average irradiance) over large skin surface. One well-designed and sufficiently powered, double-blind, sham-controlled trial indicated that t-PBM with low irradiance over a small skin surface is ineffective to treat depression. Conclusion: The use of t-PBM for Alzheimer's disease and for dementia is still at its inception; these dosimetry lessons from the use of t-PBM for depression might serve as guidance.
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Our recent study demonstrated that prefrontal transcranial photobiomodulation (tPBM) with 1064-nm laser enables significant changes in EEG rhythms, but these changes might result from the laser-induced heat rather than tPBM. This study hypothesized that tPBM-induced and heat-induced alterations in EEG power topography were significantly distinct. We performed two sets of measurements from two separate groups of healthy humans under tPBM (n = 46) and thermal stimulation (thermo_stim; n = 11) conditions. Each group participated in the study twice under true and respective sham stimulation with concurrent recordings of 64-channel EEG before, during, and after 8-min tPBM at 1064 nm or thermo_stim with temperature of 33–41 °C, respectively. After data preprocessing, EEG power spectral densities (PSD) per channel per subject were quantified and normalized by respective baseline PSD to remove the power-law effect. At the group level for each group, percent changes of EEG powers per channel were statistically compared between (1) tPBM vs light-stimulation sham, (2) thermo_stim vs heat-stimulation sham, and (3) tPBM vs thermo_stim after sham exclusion at five frequency bands using the non-parametric permutation tests. By performing the false discovery rate correction for multi-channel comparisons, we showed by EEG power change topographies that (1) tPBM significantly increased EEG alpha and beta powers, (2) the thermal stimulation created opposite effects on EEG power topographic patterns, and (3) tPBM and thermal stimulations induced significantly different topographies of changes in EEG alpha and beta power. Overall, this study provided evidence to support our hypothesis, showing that the laser-induced heat on the human forehead is not a mechanistic source causing increases in EEG power during and after tPBM.
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Background Anxiety and depression are key barriers to healthy aging and greatly heighten the risk for many negative health issues that seriously impact life quality. Aim This mini review examines the potential of low level laser treatments or photobiomodulation therapy for ameliorating severe anxiety and depression in older adults. Methods and Procedures Articles that adressed the current topic of interest extracted from PUBMED and Google Scholar were carefully and presented in narrative form. Results Photobiomodulation therapy appears to be a safe efficacious modality for ameliorating various degrees of anxiety and depression and for improving cognition, and is supported by several well established mechanisms of action at the molecular, cellular, and tissue levels. Conclusion More research to examine who might benefit most from this form of therapy, and in what respect in this area of growing global concern and few intervention options is strongly warranted.
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This presentation provides an overview of a noninvasive neurorehabilitation treatment for TBI and commonly associated neuropsychiatric problems: (1) Therapeutic effects of LED application on cognition, sleep, and PTSD; (2) Home-based TBI program, using noninvasive treatment modality, light emitting diodes (LED); (3) Virtual Care LED TBI Home Tx program for TBI and PTSD. We present the latest evidence and discuss how recent clinical research findings translate into current clinical practice. Summary: The results from the LED pilot RCT and LED clinical program evaluation showed that transcranial LED Home Tx improves cognitive (attention, executive function, learning/memory) and neuropsychiatric symptoms (mood, PTSD, sleep) in patients with chronic mild-moderate TBI. These results suggest that noninvasive, non-pharmacologic LED Home treatment with tele-health support improves daily function and neurobehavioral symptoms in chronic TBI. The LED TBI Home Tx Program, converted to Virtual Care following the COVID-19 pandemic restrictions, demonstrated higher treatment adherence and lower dropout rates, as compared to the standard In-office LED treatment. These results provide evidence that twelve-week home-based treatment of chronic mild-moderate TBI with transcranial LEDs is safe and effective for clinical use.
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.
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Significance The Monte Carlo (MC) method is widely used as the gold-standard for modeling light propagation inside turbid media like human tissues, but combating its inherent stochastic noise requires one to simulate large number photons, resulting in high computational burdens. Aim We aim to develop an effective image denoising technique using deep learning (DL) to dramatically improve low-photon MC simulation result quality, equivalently bringing further acceleration to the MC method. Approach We have developed a cascade-network combining DnCNN with UNet, in the meantime, extended a range of established image denoising neural-network architectures, including DnCNN, UNet, DRUNet, and ResMCNet, in handling three-dimensional (3-D) MC data and compared their performances against model-based denoising algorithms. We have also developed a simple yet effective approach to create synthetic datasets that can be used to train DL based MC denoisers. Results Overall, DL based image denoising algorithms exhibit significantly higher image quality improvements over traditional model-based denoising algorithms. Among the tested DL denoisiers, our Cascade network yields a 14 - 19 dB improvement in signal-noise ratio (SNR), which is equivalent to simulating 25 × to 78 × more photons. Other DL-based methods yielded similar results, with our method performing noticeably better with low-photon inputs, and ResMCNet along with DRUNet performing better with high-photon inputs. Our Cascade network achieved the highest quality when denoising complex domains, including brain and mouse atlases. Conclusion Incorporating state-of-the-art DL denoising techniques can equivalently reduce the computation time of MC simulations by one to two orders of magnitude. Our open-source MC denoising codes and data can be freely accessed at http://mcx.space/ .
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Research in the field of nano-optics is advancing by leaps and bounds, among which near-infrared (NIR) light optics have attracted much attention. NIR light has a longer wavelength than visible light, such that it can avoid shielding caused by biological tissues. This advantage has driven its importance and practicality in human treatment applications and has attracted significant attention from researchers in academia and industry. In the broad spectrum of infrared light wavelengths, the most noticeable ones are the NIR biological window I of 700-900 nm and window II of 1000-1700 nm. Luminescent materials can effectively cover the NIR biological window with different doping strategies. These doped elements are mostly transition elements with multielectron orbitals. Several nanomaterials based on narrow-spectrum lanthanides have been developed to correspond to biological applications of different wavelengths. However, this review explicitly introduces the absorption and reflection/luminescence interactions between NIR light and biological tissues independently. Unlike the adjustment of the wavelength of the lanthanide series, this review analyzes the NIR optical properties of the fourth-period element ions in transition elements (such as Cr3+ and Ni2+). These elements have a broadband wavelength of NIR light emission and higher quantum efficiency, corresponding to the absorption and emission spectrum and photobiological absorption of different NIR windows for therapeutic diagnosis. Finally, this review lists and explores other broadband NIR phosphors and has tried to discover the possibility of non-invasive precision medicine in the future.
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Chronic sleep deficiency, a public health epidemic, triggers an elevated risk for physical and mental disorders and may cause unpleasant sensations or experiences in daily life. Importantly, sleep-associated skin diseases attract public attention because most people have anxiety about their facial appearance in modern society. Amounts of health food, especially derived from edible and efficient plant extracts, have been developed for skincare via improvement of sleep quality. Mechanisms of good sleep and healthy skin have been studied, however, the relationship between sleep-promoting herbs and skincare is less elucidated. In this review, we summarize the main signaling pathways of neurotransmitter-mediated skin beauty and list dozens of functional plant extracts for sleep assistance. We conclude several plant candidates for oral cosmetics application through sleep-related neurotransmitters regulation. This review provides pieces of evidence for the application of oral cosmetic food derived from plant extracts in sleep-related beauty.
Conference Paper
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Transcranial photobiomodulation therapy (PBMT) also known as low-level laser therapy (LLLT) relies on the use of red/NIR light to stimulate, preserve and regenerate cells and tissues. In this review, we will present the most important laser types and sources used in the treatment of the brain, required energy densities to provide treatment, and laser delivery techniques to the brain through the cranium, eye, internal ear, and nostril. Various forms of light therapy have been practiced all over the world for many years. Among them, laser therapy has flourished in recent years. More and more laser equipment is being used in this area. The use of PBMT for neuronal stimulation has been studied in various animal and human models and has been shown to improve cerebral metabolic activity and blood flow and provide neuroprotection through anti-inflammatory and antioxidant pathways. In recent years, the concept of thermotherapy for the treatment of brain tumors has become more widespread. Traditionally, heat therapy is divided into hyperthermia, with a moderate increase in the temperature of the treated tissue above the physiological baseline level, and heat ablation, in which even higher temperatures are reached. Recently, intranasal light therapy, light delivery to the brain through the ear and other channels have become attractive and potential treatments for brain diseases. Here we summarize the various methods of delivering light through the nostrils and ear canals using lasers or light-emitting diodes (LEDs), which can be used alone or in combination with transcranial devices or (applied directly to the scalp) to treat a wide range of brain conditions such as the lungs cognitive impairment, Alzheimer's disease, Parkinson's disease, cerebrovascular disease, depression and anxiety, and insomnia. Evidence shows that low-intensity laser therapy improves blood rheology and cerebral blood flow, so there is no need to pierce blood vessels.
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Understanding the compartment fire behavior has a vital importance for fire protection engineers. For design purposes, whether to use a prescriptive code or performance based on design, life safety and property protection issues are required to be assessed. The use of design fires in computer modelling is the general method to determine fire safety. However, these computer models are generally limited to the input of one design fire, with consideration of the complex interaction between fuel packages and the compartment environment being simplified. Of particular interest is the Heat Release Rate, HRR, as this is the commonly prescribed design parameter for fire modelling. If the HRR is not accurate then it can be subsequently argued that the design scenario may be flawed. Therefore, the selection of the most appropriate fire design scenario is critical, and an increased level of understanding of compartment behavior is an invaluable aid to fire engineering assumptions. This thesis studies 3 types of pool fire geometry to enhance the understanding of the impact and interaction that the size and location of pool fires within an enclosure have upon the compartment fire behavior, also Ethanol pool fires were used. In this present work, we have carried out to analysis the effect of water to extinguish the fire and it and it's tested in 4 different ways with and without water. Also in the result, we can see the effect of water to visibility and also the concentration of air.
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Discusses and reviews data regarding possible utility of photobiomodulation for mitigating severe depression and anxiety in the elderly.
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Transcranial near-infrared radiation (NIR) is an innovative treatment for major depressive disorder (MDD), but clinical evidence for its efficacy is limited. Our objective was to investigate the tolerability and efficacy of NIR in patients with MDD. We conducted a proof of concept, prospective, double-blind, randomized study of 6 sessions of NIR versus sham treatment for patients with MDD, using a crossover design. Four patients with MDD with mean age 47 ± 14 (SD) years (1 woman and 3 men) were exposed to irradiance of 700 mW/cm(2) and a fluence of 84 J/cm(2) for a total NIR energy of 2.40 kJ delivered per session for 6 sessions. Baseline mean HAM-D17 scores decreased from 19.8 ± 4.4 (SD) to 13 ± 5.35 (SD) after treatment (t = 7.905; df = 3; P = 0.004). Patients tolerated the treatment well without any serious adverse events. These findings confirm and extend the preliminary data on NIR as a novel intervention for patients with MDD, but further clinical trials are needed to better understand the efficacy of this new treatment. This trial is registered with ClinicalTrials.gov NCT01538199.
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Traumatic brain injury (TBI) is a growing health concern affecting civilians and military personnel. In this review, treatments for the chronic TBI patient are discussed, including pharmaceuticals, nutraceuticals, cognitive therapy, and hyperbaric oxygen therapy. All available literature suggests a marginal benefit with prolonged treatment courses. An emerging modality of treatment is near-infrared light (NIR), which has benefit in animal models of stroke, spinal cord injury, optic nerve injury and TBI and in human trials for stroke and TBI. The extant literature is confounded by variable degrees of efficacy and a bewildering array of treatment parameters. Some data indicates that diodes emitting low level NIR often have failed to demonstrate therapeutic efficacy, perhaps due to failing to deliver sufficient radiant energy to the necessary depth. As part of this review, we present a retrospective case series using high power laser NIR phototherapy with a Class IV laser to treat TBI. We demonstrate greater clinical efficacy with higher fluence; in contrast to the bimodal model of efficacy previously proposed. In ten patients with chronic TBI (average time since injury 9.3 years) given 10 treatments over the course of two months using a high power NIR laser (13.2 W/0.89 cm2 810nm or 9 W/0.89 cm2 at 810 and 980nm), symptoms of headache, sleep disturbance, cognition, mood dysregulation, anxiety, and irritability improved. Symptoms were monitored by depression scales and a novel patient diary system specifically designed for this study. NIR in the power range of 10-15 Watts at 810 and 980nm can safely and effectively treat chronic symptoms of TBI. The clinical benefit and effects of infrared phototherapy on mitochondrial function and secondary molecular events are discussed in the context of adequate radiant energy penetration.
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Abstract: Traumatic brain injury (TBI) is a growing health concern effecting civilians and military personnel. Research has yielded a better understanding of the pathophysiology of TBI, but effective treatments have not been forthcoming. Near-infrared light (NIR) has shown promise in animal models of both TBI and stroke. Yet, it remains unclear if sufficient photonic energy can be delivered to the human brain to yield a beneficial effect. This paper reviews the pathophysiology of TBI and elaborates the physiological effects of NIR in the context of this pathophysiology. Pertinent aspects of the physical properties of NIR, particularly in regards to its interactions with tissue, provide the background for understanding this critical issue of light penetration through tissue. Our recent tissue studies demonstrate no penetration of low level NIR energy through 2 mm of skin or 3 cm of skull and brain. However, at 10–15 W, 0.45%–2.90% of 810 nm light penetrated 3 cm of tissue. A 15 W 810 nm device (continuous or non-pulsed) NIR delivered 2.9% of the surface power density. Pulsing at 10 Hz reduced the dose of light delivered to the surface by 50%, but 2.4% of the surface energy reached the depth of 3 cm. Approximately 1.22% of the energy of 980 nm light at 10–15 W penetrated to 3 cm. These data are reviewed in the context of the literature on low-power NIR penetration, wherein less than half of 1% of the surface energy could reach a depth of 1 cm. NIR in the power range of 10–15 W at 810 and 980 nm can provide fluence within the range shown to be biologically beneficial at 3 cm depth. A companion paper reviews the clinical data on the treatment of patients with chronic TBI in the context of the current literature.
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The use of transcranial low-level laser (light) therapy (tLLLT) to treat stroke and traumatic brain injury (TBI) is attracting increasing attention. We previously showed that LLLT using an 810-nm laser 4 h after controlled cortical impact (CCI)-TBI in mice could significantly improve the neurological severity score, decrease lesion volume, and reduce Fluoro-Jade staining for degenerating neurons. We obtained some evidence for neurogenesis in the region of the lesion. We now tested the hypothesis that tLLLT can improve performance on the Morris water maze (MWM, learning, and memory) and increase neurogenesis in the hippocampus and subventricular zone (SVZ) after CCI-TBI in mice. One and (to a greater extent) three daily laser treatments commencing 4-h post-TBI improved neurological performance as measured by wire grip and motion test especially at 3 and 4 weeks post-TBI. Improvements in visible and hidden platform latency and probe tests in MWM were seen at 4 weeks. Caspase-3 expression was lower in the lesion region at 4 days post-TBI. Double-stained BrdU-NeuN (neuroprogenitor cells) was increased in the dentate gyrus and SVZ. Increases in double-cortin (DCX) and TUJ-1 were also seen. Our study results suggest that tLLLT may improve TBI both by reducing cell death in the lesion and by stimulating neurogenesis. (C) 2014 Society of Photo-Optical Instrumentation Engineers (SPIE)
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Transcranial low-level laser (light) therapy (LLLT) is a new non-invasive approach to treating a range of brain disorders including traumatic brain injury (TBI). We (and others) have shown that applying near-infrared light to the head of animals that have suffered TBI produces improvement in neurological functioning, lessens the size of the brain lesion, reduces neuroinflammation, and stimulates the formation of new neurons. In the present study we used a controlled cortical impact TBI in mice and treated the mice either once (4 h post-TBI, 1-laser), or three daily applications (3-laser) with 810 nm CW laser 36 J/cm(2) at 50 mW/cm(2) . Similar to previous studies, the neurological severity score improved in laser-treated mice compared to untreated TBI mice at day 14 and continued to further improve at days 21 and 28 with 3-laser being better than 1-laser. Mice were sacrificed at days 7 and 28 and brains removed for immunofluorescence analysis. Brain-derived neurotrophic factor (BDNF) was significantly upregulated by laser treatment in the dentate gyrus of the hippocampus (DG) and the subventricular zone (SVZ) but not in the perilesional cortex (lesion) at day 7 but not at day 28. Synapsin-1 (a marker for synaptogenesis, the formation of new connections between existing neurons) was significantly upregulated in lesion and SVZ but not DG, at 28 days but not 7 days. The data suggest that the benefit of LLLT to the brain is partly mediated by stimulation of BDNF production, which may in turn encourage synaptogenesis. Moreover the pleiotropic benefits of BDNF in the brain suggest LLLT may have wider applications to neurodegenerative and psychiatric disorders. Neurological Severity Score (NSS) for TBI mice.
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Several studies demonstrate the benefits of low-power light therapy on wound healing. However, the use of LED as a therapeutic resource remains controversial. There are questions regarding the equality or not of biological effects promoted by LED and LASER. One objective of this review was to determine the biological effects that support the use of LED on wound healing. Another objective was to identify LED´s parameters for the treatment of wounds. The biological effects and parameters of LED will be compared to those of LASER. Literature was obtained from online databases such as Medline, PubMed, Science Direct and Scielo. The search was restricted to studies published in English and Portuguese from 1992 to 2012. Sixty-eight studies in vitro and in animals were analyzed. LED and LASER promote similar biological effects, such as decrease of inflammatory cells, increased fibroblast proliferation, stimulation of angiogenesis, granulation tissue formation and increased synthesis of collagen. The irradiation parameters are also similar between LED and LASER. The biological effects are dependent on irradiation parameters, mainly wavelength and dose. This review elucidates the importance of defining parameters for the use of light devices.
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This pilot, open-protocol study examined whether scalp application of red and near-infrared (NIR) light-emitting diodes (LED) could improve cognition in patients with chronic, mild traumatic brain injury (mTBI). Application of red/NIR light improves mitochondrial function (especially in hypoxic/compromised cells) promoting increased ATP important for cellular metabolism. Nitric oxide is released locally, increasing regional cerebral blood flow. LED therapy is non-invasive, painless, and non-thermal (FDA-cleared, non-significant risk device). Eleven chronic, mTBI participants (26-62 Yr, 6M) with non-penetrating head injury and persistent cognitive dysfunction were treated for 18 outpatient sessions (MWF, 6 Wks), starting at 10 Mo to 8 Yr post- mTBI (MVA or sports-related; and one participant, IED blast injury). Four had a history of multiple concussions. Each LED cluster head (2.1" diameter, 500mW, 22.2mW/cm2) was applied for 10 min to each of 11 scalp placements (13 J/cm2). LEDs were placed on the midline from front-to-back hairline; and bilaterally on frontal, parietal, and temporal areas. Neuropsychological testing was performed pre- LED, and at 1 Wk, 1 and 2 Mo post- the 18th treatment. A significant linear trend was observed for the effect of LED treatment over time for Stroop test for Executive Function, Trial 3 inhibition (p=.004); Stroop, Trial 4 inhibition switching (p=.003); California Verbal Learning Test (CVLT)-II, Total Trials 1-5 (p=.003); and CVLT-II, Long Delay Free Recall (p=.006). Participants reported improved sleep, and fewer PTSD symptoms, if present. Participants and family reported better ability to perform social, interpersonal and occupational functions. These open-protocol data suggest placebo controlled studies are warranted.
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The use of low level laser (light) therapy (LLLT) has recently expanded to cover areas of medicine that were not previously thought of as the usual applications such as wound healing and inflammatory orthopedic conditions. One of these novel application areas is LLLT for muscle fatigue and muscle injury. Since it is becoming agreed that mitochondria are the principal photoacceptors present inside cells, and it is known that muscle cells are exceptionally rich in mitochondria, this suggests that LLLT should be highly beneficial in muscle injuries. The ability of LLLT to stimulate stem cells and progenitor cells means that muscle satellite cells may respond well to LLLT and help muscle repair. Furthermore the ability of LLLT to reduce inflammation and lessen oxidative stress is also beneficial in cases of muscle fatigue and injury. This review covers the literature relating to LLLT and muscles in both preclinical animal experiments and human clinical studies. Athletes, people with injured muscles, and patients with Duchenne muscular dystrophy may all benefit.
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Low-level laser (light) therapy (LLLT) has been clinically applied around the world for a spectrum of disorders requiring healing, regeneration and prevention of tissue death. One area that is attracting growing interest in this scope is the use of transcranial LLLT to treat stroke and traumatic brain injury (TBI). We developed a mouse model of severe TBI induced by controlled cortical impact and explored the effect of different treatment schedules. Adult male BALB/c mice were divided into 3 broad groups (a) sham-TBI sham-treatment, (b) real-TBI sham-treatment, and (c) real-TBI active-treatment. Mice received active-treatment (transcranial LLLT by continuous wave 810 nm laser, 25 mW/cm(2), 18 J/cm(2), spot diameter 1 cm) while sham-treatment was immobilization only, delivered either as a single treatment at 4 hours post TBI, as 3 daily treatments commencing at 4 hours post TBI or as 14 daily treatments. Mice were sacrificed at 0, 4, 7, 14 and 28 days post-TBI for histology or histomorphometry, and injected with bromodeoxyuridine (BrdU) at days 21-27 to allow identification of proliferating cells. Mice with severe TBI treated with 1-laser Tx (and to a greater extent 3-laser Tx) had significant improvements in neurological severity score (NSS), and wire-grip and motion test (WGMT). However 14-laser Tx provided no benefit over TBI-sham control. Mice receiving 1- and 3-laser Tx had smaller lesion size at 28-days (although the size increased over 4 weeks in all TBI-groups) and less Fluoro-Jade staining for degenerating neurons (at 14 days) than in TBI control and 14-laser Tx groups. There were more BrdU-positive cells in the lesion in 1- and 3-laser groups suggesting LLLT may increase neurogenesis. Transcranial NIR laser may provide benefit in cases of acute TBI provided the optimum treatment regimen is employed.
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There is growing evidence that stress causes a decrease of neurogenesis in the dentate gyrus and antidepressant treatment in turn stimulates the cell proliferation in the dentate gyrus. This has led to the hypothesis that a decreased neurogenesis might be linked to the pathophysiology of major depression. The article reviews the relationship of depressive-like behavior and neurogenesis in three animal models of depression with high validity: learned helplessness, chronic mild stress and chronic psychosocial stress of the tree shrew. All animal models provide evidence that stress which can lead to depressive-like behavior, in parallel causes a decrease of neurogenesis; vice versa, antidepressant treatment is able to revert not only behavioral changes but also to normalize neurogenesis. But the animal models argue against the notion that decreases of neurogenesis are the cause or the consequence of depressive-like behavior since depressive-like behavior can occur without impairments in neurogenesis and decreasing neurogenesis does not neccessarily lead to depressive-like behavior. This suggests that neurogenesis does not directly control affect but is tightly connected to the modulation of affect by stress and antidepressant measures.
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We investigated the effects of lamotrigine, aripiprazole and escitalopram administration and experimental depression on lipid peroxidation (LP) and antioxidant levels in cortex of the brain in rats. Forty male wistar rats were randomly divided into five groups. First group was used as control although second group was depression-induced group. Aripiprazole, lamotrigine and escitalopram per day were orally supplemented to chronic mild stress (CMS) depression-induced rats constituting the third, fourth and fifth groups for 28 days, respectively. Depression resulted in significant decrease in the glutathione peroxidase (GSH-Px) activity, reduced glutathione and vitamin C of cortex of the brain although their levels and beta-carotene concentrations were increased by the three drugs administrations to the animals of CMS induced depression group. The LP levels in the cortex of the brain and plasma of depression group were elevated although their levels were decreased by the administrations. The increases of antioxidant values in lamotrigine group were higher according to aripiprazole and escitalopram supplemented groups. Vitamin A level did not change in the five groups. In conclusion, the experimental depression is associated with elevated oxidative stress although treatment with lamotrigine has most protective effects on the oxidative stress within three medicines.
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Two chronic, traumatic brain injury (TBI) cases, where cognition improved following treatment with red and near-infrared light-emitting diodes (LEDs), applied transcranially to forehead and scalp areas, are presented. Significant benefits have been reported following application of transcranial, low-level laser therapy (LLLT) to humans with acute stroke and mice with acute TBI. These are the first case reports documenting improved cognitive function in chronic, TBI patients treated with transcranial LED. Treatments were applied bilaterally and to midline sagittal areas using LED cluster heads [2.1″ diameter, 61 diodes (9 × 633 nm, 52 × 870 nm); 12-15 mW per diode; total power: 500 mW; 22.2 mW/cm(2); 13.3 J/cm(2) at scalp (estimated 0.4 J/cm(2) to cortex)]. Seven years after closed-head TBI from a motor vehicle accident, Patient 1 began transcranial LED treatments. Pre-LED, her ability for sustained attention (computer work) lasted 20 min. After eight weekly LED treatments, her sustained attention time increased to 3 h. The patient performs nightly home treatments (5 years); if she stops treating for more than 2 weeks, she regresses. Patient 2 had a history of closed-head trauma (sports/military, and recent fall), and magnetic resonance imaging showed frontoparietal atrophy. Pre-LED, she was on medical disability for 5 months. After 4 months of nightly LED treatments at home, medical disability discontinued; she returned to working full-time as an executive consultant with an international technology consulting firm. Neuropsychological testing after 9 months of transcranial LED indicated significant improvement (+1, +2SD) in executive function (inhibition, inhibition accuracy) and memory, as well as reduction in post-traumatic stress disorder. If she stops treating for more than 1 week, she regresses. At the time of this report, both patients are continuing treatment. Transcranial LED may improve cognition, reduce costs in TBI treatment, and be applied at home. Controlled studies are warranted.
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Transcranial laser therapy (TLT) was tested for efficacy in a mouse model of Alzheimer's disease (AD) using a near-infrared energy laser system. TLT is thought to stimulate ATP production, increase mitochondrial activity, and help maintain neuronal function. Studies were performed to determine the effect of TLT in an amyloid-β protein precursor (AβPP) transgenic mouse model. TLT was administered 3 times/week at various doses, starting at 3 months of age, and was compared to a control group (no laser treatment). Treatment was continued for a total of six months. Animals were examined for amyloid load, inflammatory markers, brain amyloid-β (Aβ) levels, plasma Aβ levels, cerebrospinal fluid Aβ levels, soluble AβPP (sAβPP) levels, and behavioral changes. The numbers of Aβ plaques were significantly reduced in the brain with administration of TLT in a dose-dependent fashion. Administration of TLT was associated with a dose-dependent reduction in amyloid load. All TLT doses mitigated the behavioral effects seen with advanced amyloid deposition and reduce the expression of inflammatory markers in the AβPP transgenic mice. All TLT doses produced an increase in sAβPPα and a decrease in CTFβ levels consistent with inhibition of the β-secretase activity. In addition, TLT showed an increase in ATP levels, mitochondrial function, and c-fos suggesting an overall improvement in neurological function. These studies suggest that TLT is a potential candidate for treatment of AD.
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The etiology of major depression (MDD), a common and complex disorder, remains obscure. Gene expression profiling was conducted on post-mortem brain tissue samples from Brodmann Area 10 (BA10) in the prefrontal cortex from psychotropic drug-free persons with a history of MDD and age, gender, and post-mortem interval-matched normal controls (n=14 pairs of subjects). Microarray analysis was conducted using the Affymetrix Exon 1.0 ST arrays. A set of differential expression changes was determined by dual-fold change-probability criteria (∣average log ratios∣>0.585 [equivalent to a 1.5-fold difference in either direction], P<0.01), whereas molecular pathways of interest were evaluated using Gene Set Enrichment Analysis software. The results strongly implicate increased apoptotic stress in the samples from the MDD group. Three anti-apoptotic factors, Y-box-binding protein 1, caspase-1 dominant-negative inhibitor pseudo-ICE, and the putative apoptosis inhibitor FKGS2, were over-expressed. Gene set analysis suggested up-regulation of a variety of pro- and anti-inflammatory cytokines, including interleukin 1α (IL-1α), IL-2, IL-3, IL-5, IL-8, IL-9, IL-10, IL-12A, IL-13, IL-15, IL-18, interferon gamma (IFNγ), and lymphotoxin α (TNF superfamily member 1). The genes showing reduced expression included metallothionein 1M (MT1M), a zinc-binding protein with a significant function in the modulation of oxidative stress. The results of this study indicate that post-mortem brain tissue samples from BA10, a region that is involved in reward-related behavior, show evidence of local inflammatory, apoptotic, and oxidative stress in MDD.
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An alternative approach in the treatment of acne vulgaris is photodynamic therapy (PDT) that uses light and aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) production to eradicate Propionibacterium acnes found in acne lesions. PpIX formation is dependent on ALA percutaneaous penetration. In this study, to enhance ALA penetration and subsequent accumulation of PpIX, skin temperature was increased with radiant infrared (IR) prior to ALA-PDT application and compared to ALA-PDT alone in the treatment of inflammatory acne. Ten patients exhibiting inflammatory acne with a lesion count of > or =10 were assigned to a split face or split back group. One side was pre-treated for 15 minutes with radiant IR light emitting diode (LED) (970 nm), while the other side was used as control. ALA was then applied after which PDT LED (630 nm) was performed on the entire face or back surface. Blinded lesion counts and clinical global assessment of severity were performed based on digital photographs before and 4 weeks after the PDT procedure. This randomized, controlled, and rater-blinded trial revealed a significant difference in median reduction of inflammatory lesions on the IR pre-treated (73%, 95% confidence interval (CI) 51-81%) versus the control side (38%, 95% CI 8-55%) 1 month after PDT (P<0.0001). Clinical assessment of severity was also significantly lower on the IR-treated side than on the control side (median 1, 95% CI 0.74-1.34 vs. 2, 95% CI 1.17-1.72). No unusual treatment-related adverse effects were observed. The reported therapeutic effects may be due to enhanced induction of alterations in transcutaneous diffusion kinetics of the photosensitizer at higher skin temperature and/or conversion of ALA to PpIX. Pre-PDT radiant IR LED exposure appears to be a promising method to enhance PDT efficacy for the treatment of acne lesions.