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Background:
Transcranial photobiomodulation (tPBM) has recently emerged as a potential cognitive enhancement technique and clinical treatment for various neuropsychiatric and neurodegenerative disorders by delivering invisible near-infrared light to the scalp and increasing energy metabolism in the brain.
Objective:
We assessed whether transcran...
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Diffuse correlation spectroscopy (DCS) is a non-invasive optical technology for the assessment of an index of cerebral blood flow (CBFi). Analytical methods that model the head as a three-layered medium (i.e., scalp, skull, brain) are becoming more commonly used to minimize the contribution of extracerebral layers to the measured DCS signal in adul...
Citations
... However, its efficacy has not been consistent across all patients, similar to other noninvasive neuromodulation techniques [17]. Previous studies have reported non-responders to tPBM [18] and dosage-related inter-subjective variability influencing its treatment outcomes [19]. In this regard, the early prediction of the tPBM effectiveness could guide patients towards alternative treatment options, thereby increasing the cost-effectiveness of tPBM treatment in the healthcare and medical fields. ...
Transcranial photobiomodulation (tPBM) has been widely studied for its potential to enhance cognitive functions of the elderly. However, its efficacy varies, with some individuals exhibiting no significant response to the treatment. Considering these inconsistencies, we introduce a machine learning approach aimed at distinguishing between individuals that respond and do not respond to tPBM treatment based on functional near-infrared spectroscopy (fNIRS) acquired before the treatment. We measured nine cognitive scores and recorded fNIRS data from 62 older adults with cognitive decline (43 experimental and 19 control subjects). The experimental group underwent tPBM intervention over a span of 12 weeks. Based on the comparison of the global cognitive score (GCS), merging the nine cognitive scores into a single representation, acquired before and after tPBM treatment, we classified all participants as responders or non-responders to tPBM with a threshold for the GCS change. The fNIRS data were recorded during the resting state, recognition memory task (RMT), Stroop task, and verbal fluency task. A regularized support vector machine was utilized to classify the responders and non-responders to tPBM. The most promising performance of our machine learning model was observed when using the fNIRS data collected during the RMT, which yielded an accuracy of 0.8537, an F1-score of 0.8421, sensitivity of 0.7619, and specificity of 0.95. To the best of our knowledge, this is the first study to demonstrate the feasibility of predicting the tPBM efficacy. Our approach is expected to contribute to more efficient treatment planning by excluding ineffective treatment options.
... EEG recordings were performed before and after the t-PBM session. t-PBM significantly boosted beta (t = 2.91, df = 7, p < 0.03) and gamma (t = 3.02, df = 7, p < 0.02) EEG spectral powers in eyes-open recordings and gamma power (t = 3.61, df = 6, p < 0.015) in eyes-closed recordings, with the largest effects in the posterior regions [67]. ...
... Non-invasive brain stimulation techniques could help alleviate these changes, and we consider t-PBM to be a promising option. Spera et al. (2021) [67] conducted a study demonstrating that t-PBM, delivered through a device comprising four LED clusters, significantly boosted high-frequency neural activity in the gamma and beta bands. This enhancement, believed to support advanced cognitive functions, occurred after just one 20 min exposure targeting the forebrain. ...
Down syndrome (DS) is the leading genetic cause of intellectual disability globally, affecting about 1 in every 800 births. Individuals with DS often face various neuropsychiatric conditions alongside intellectual disabilities due to altered brain development. Despite the diverse phenotypic expressions of DS, typical physical characteristics frequently influence language development and acquisition. EEG studies have identified abnormal oscillatory patterns in individuals with DS. Emerging interventions targeting the enhancement of gamma (40 Hz) neuronal oscillations show potential for improving brain electrical activity and cognitive functions in this population. However, effective cognitive interventions for DS remain scarce. Extensive research indicates that transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light can penetrate deeply into the cerebral cortex, modulate cortical excitability, and enhance cerebral perfusion and oxygenation. Furthermore, t-PBM has been shown to improve cognitive functions such as language, attention, inhibition, learning, and memory, including working memory. This study presents the rationale and design of an ongoing randomized, sham-controlled clinical trial aimed at assessing the effectiveness of t-PBM using NIR light in enhancing the language abilities of individuals with DS.
... However, more research is needed to determine t-PBM efficacy and mechanisms of action. In fact, our group has also theorized that local electromagnetic neuromodulation-in the absence of sufficient photon deposition at brain target indirect but local mechanisms of action-might explain the immediate changes in neurophysiology induced by lowpower t-PBM [119]. Future directions should include conducting more preclinical studies and randomized sham-controlled clinical trials with larger sample sizes and comprehensive biomarker analyses. ...
Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and Down syndrome (DS) significantly impact social, communicative, and behavioral functioning. Transcranial photobiomodulation (t-PBM) with near-infrared light is a promising non-invasive neurostimulation technique for neuropsychiatric disorders, including NDDs. This narrative review aimed to examine the preclinical and clinical evidence of photobiomodulation (PBM) in treating NDDs.
A comprehensive search across six databases was conducted, using a combination of MeSH terms and title/abstract keywords: “photobiomodulation”, “PBM”, “neurodevelopmental disorders”, “NDD”, and others. Studies applying PBM to diagnosed NDD cases or animal models replicating NDDs were included. Protocols, reviews, studies published in languages other than English, and studies not evaluating clinical or cognitive outcomes were excluded.
Nine studies were identified, including one preclinical and eight clinical studies (five on ASD, two on ADHD, and one on DS). The reviewed studies encompassed various t-PBM parameters (wavelengths: 635–905 nm) and targeted primarily frontal cortex areas. t-PBM showed efficacy in improving disruptive behavior, social communication, cognitive rigidity, sleep quality, and attention in ASD; in enhancing attention in ADHD; and in improving motor skills and verbal fluency in DS. Minimal adverse effects were reported. Proposed mechanisms involve enhanced mitochondrial function, modulated oxidative stress, and reduced neuroinflammation.
t-PBM emerges as a promising intervention for NDDs, with potential therapeutic effects across ASD, ADHD, and DS. These findings underscore the need for further research, including larger-scale, randomized sham-controlled clinical trials with comprehensive biomarker analyses, to optimize treatment parameters and understand the underlying mechanisms associated with the effects of t-PBM.
... The field of PBM has witnessed significant progress in improving brain stimulation parameters. Notably, the shift from continuous to pulsed stimulation has shown potential benefits, enhancing tissue absorption responses and possibly inducing specific brain wave rhythms, such as alpha waves at 10 Hz and gamma waves at 40 Hz (10). Furthermore, intranasal PBM may be related to direct or indirect stimulation of deeper brain regions (11), such as ventromedial prefrontal cortex and ventromedial orbitofrontal cortex (12). ...
Introduction
Photobiomodulation (PBM) is a novel strategy for cognitive enhancement by improving brain metabolism and blood flow. It is potentially beneficial for patients with Alzheimer’s disease (AD). We present a study protocol for a randomised controlled trial designed to evaluate the efficacy and safety of PBM.
Method and analysis
This is a single-centre, parallel-group, randomised, sham-controlled study. We enroll patients with mild cognitive impairment or dementia due to AD and assigned them to receive either active or sham stimulation at home for 12 weeks, with three sessions per week (20 min each). The stimulation involves invisible near-infrared light delivered by five applicators (one in a nostril, one on the frontal scalp, and three on the occipital scalp). The primary outcome will be the mean change in the Alzheimer Disease Assessment Scale-cognition from baseline to Week 12. We will also measure cognitive function, activity of daily living, behavioral and psychological symptoms, and caregiver burden. We will collect data at clinics at baseline and Week 12 and remotely at home. We estimate a sample size of 30 (20 active and 10 sham) based on an expected mean difference of −6.9 and an SD of 4.8. We use linear models for the statistical analysis.
Ethics and dissemination
The National Center of Neurology and Psychiatry Clinical Research Review Board (CRB3200004) approved this study. The results of this study will be published in a scientific peer-reviewed journal. Trial registration details Japan Registry of Clinical Trials jRCTs032230339.
... In the reported PBM studies for physiological characterization, light in continuous mode was the most used, whereas in studies of PBM in degenerative brain diseases, light in pulsed mode was more common. Among the included articles (n = 97), one study in AD patients compared both continuous and pulsed stimulation, observing that continuous stimulation caused a significant and large enhancement of neural activity in the gamma band [89]. One article assessing the effect of PBM in cortical excitability studied the use of pulsed NIR light in the 5 Hz, 10 Hz and 20 Hz frequencies, with a 50% duty cycle. ...
A systematic review was conducted to determine the trends in devices and parameters used for brain photobiomodulation (PBM). The revised studies included clinical and cadaveric approaches, in which light stimuli were applied to the head and/or neck. PubMed, Scopus, Web of Science and Google Scholar databases were used for the systematic search. A total of 2133 records were screened, from which 97 were included in this review. The parameters that were extracted and analysed in each article were the device design, actuation area, actuation site, wavelength, mode of operation, power density, energy density, power output, energy per session and treatment time. To organize device information, 11 categories of devices were defined, according to their characteristics. The most used category of devices was laser handpieces, which relate to 21% of all devices, while 28% of the devices were not described. Studies for cognitive function and physiological characterisation are the most well defined ones and with more tangible results. There is a lack of consistency when reporting PBM studies, with several articles under defining the stimulation protocol, and a wide variety of parameters used for the same health conditions (e.g., Alzheimer’s or Parkinson’s disease) resulting in positive outcomes. Standardization for the report of these studies is warranted, as well as sham-controlled comparative studies to determine which parameters have the greatest effect on PBM treatments for different neurological conditions.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12984-024-01351-8.
... However, studies on tPBM-induced electrophysiological effects in the human brain are limited, with only a few publications [31][32][33][34] besides ours [26,35,36] in the last 4-5 years. All these studies reported acute alterations in electroencephalogram (EEG) power by tPBM, without any repeated tPBM treatment, compared to sham stimulation. ...
Transcranial photobiomodulation (tPBM) has been suggested as a non-invasive neuromodulation tool. The repetitive administration of light-emitting diode (LED)-based tPBM for several weeks significantly improves human cognition. To understand the electrophysiological effects of LED-tPBM on the human brain, we investigated alterations by repeated tPBM in vigilance performance and brain networks using electroencephalography (EEG) in healthy participants. Active and sham LED-based tPBM were administered to the right forehead of young participants twice a week for four weeks. The participants performed a psychomotor vigilance task (PVT) during each tPBM/sham experiment. A 64-electrode EEG system recorded electrophysiological signals from each participant during the first and last visits in a 4-week study. Topographical maps of the EEG power enhanced by tPBM were statistically compared for the repeated tPBM effect. A new data processing framework combining the group’s singular value decomposition (gSVD) with eLORETA was implemented to identify EEG brain networks. The reaction time of the PVT in the tPBM-treated group was significantly improved over four weeks compared to that in the sham group. We observed acute increases in EEG delta and alpha powers during a 10 min LED-tPBM while the participants performed the PVT task. We also found that the theta, beta, and gamma EEG powers significantly increased overall after four weeks of LED-tPBM. Combining gSVD with eLORETA enabled us to identify EEG brain networks and the corresponding network power changes by repeated 4-week tPBM. This study clearly demonstrated that a 4-week prefrontal LED-tPBM can neuromodulate several key EEG networks, implying a possible causal effect between modulated brain networks and improved psychomotor vigilance outcomes.
... According to this issue, in 2018 it was reported that the low-frequency waves, especially delta rhythm undergoes more impairment in brain dysfunction such as epilepsy; while the intermediate frequency alpha wave did not show any surprise dataset, because the main source for its recording is the occipital lobe (46). In addition, more dynamic mitochondria due to supporting high oxygen/ glucose consumption and cerebral blood flow (CBF) have also been shown to affect brain activity, especially at high frequencies (47). Interestingly, the activity of mitochondria is reported to almost double in rats with a sesamin diet (0.5%) (48). ...
Objectives:
Seizure is a prevalent disorder reflected by powerful and sudden activity of neural networks in the brain that leads to tonic-clonic attacks. These signs may be due to an increase in excitatory/inhibitory neurotransmitters ratio. So, the current experiment aimed to examine the seizure and neurobehavioral parameters, as well as the hippocampus local electroencephalogram (EEG) after seizure with and without sesamin pretreatment.
Materials and methods:
Sesamin (15, 30, and 60 mg/kg/5 ml, intraperitoneal or IP, vehicle: dimethyl sulfoxide or DMSO, for 3 days) was administrated before pentylenetetrazol (PTZ) (60 mg/kg/10 ml, IP, vehicle: saline), which induces acute seizure in adult male Wistar rats (230 ± 20 g, six weeks old). Different phases of seizures (score, latency, duration, and frequency), behavioral parameters (passive avoidance memory, anxiety, and locomotor activity), and hippocampus local EEG were evaluated after the injections. At the end of the experiments, oxidative stress markers plus gene expression of phosphoinositide 3-kinase/protein kinase B or PI3K/Akt mRNA were measured in the hippocampus.
Results:
Pretreatment with sesamin (30 mg/kg) could significantly decrease seizure scores and oxidative stress in the hippocampus. PTZ injection induced EEG deficits and neurobehavioral impairments which were significantly decreased by sesamin, especially in Beta, Theta, and delta EEG waves. Also, the expression of PI3K/Akt significantly increased in the sesamin (30 mg/kg) group in comparison with the PTZ group.
Conclusion:
Sesamin could prevent seizure attacks and neurobehavioral and EEG deficits induced by pentylenetetrazol, probably through the PI3K/Akt signaling pathway.
... Transcranial photobiomodulation (t-PBM) is a novel, non-invasive, neuromodulation intervention with the potential to become an at-home, wearable treatment for AD [21]. It uses non-retinal exposure to specific wavelengths, either visible red light (600 to 700 nm) or Near-Infrared Radiation (NIR, usually 810-1100 nm), to stimulate, heal, and repair damaged or dying cells and tissue. ...
... Given the ever-increasing prevalence of AD [1] and the lack of effective, easily accessible treatments, the need for novel treatment strategies is dire. t-PBM is an emerging neuromodulation therapy that has a potential to treat AD [21,25,27,28,33,34,[42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58]62,63,[89][90][91], with a favorable safety profile [33,[59][60][61]. Our study will be the first to evaluate the effects of t-PBM in aMCI and mild dementia due to AD in a parallel group, sham-controlled, 8-week randomized, multi-site clinical trial. ...
Background:
Alzheimer's disease's (AD) prevalence is projected to increase as the population ages and current treatments are minimally effective. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates into the cerebral cortex, stimulates the mitochondrial respiratory chain, and increases cerebral blood flow. Preliminary data suggests t-PBM may be efficacious in improving cognition in people with early AD and amnestic mild cognitive impairment (aMCI).
Methods:
In this randomized, double-blind, placebo-controlled study with aMCI and early AD participants, we will test the efficacy, safety, and impact on cognition of 24 sessions of t-PBM delivered over 8 weeks. Brain mechanisms of t-PBM in this population will be explored by testing whether the baseline tau burden (measured with 18F-MK6240), or changes in mitochondrial function over 8 weeks (assessed with 31P-MRSI), moderates the changes observed in cognitive functions after t-PBM therapy. We will also use changes in the fMRI Blood-Oxygenation-Level-Dependent (BOLD) signal after a single treatment to demonstrate t-PBM-dependent increases in prefrontal cortex blood flow.
Conclusion:
This study will test whether t-PBM, a low-cost, accessible, and user-friendly intervention, has the potential to improve cognition and function in an aMCI and early AD population.
... However, studies on tPBM-induced electrophysiological effects in the human brain are limited, with only a few publications [17,[31][32][33][34] besides ours [26,35,36] in the last 4-5 years. All these studies reported acute alterations in electroencephalogram (EEG) power by tPBM compared to sham stimulation, without any repeated tPBM treatment. ...
Transcranial photobiomodulation (tPBM) has been suggested as a non-invasive neuromodulation tool. Repetitive administration of light-emitting diode (LED)-based tPBM for several weeks significantly improved human cognition. To understand the electrophysiological effects of LED-tPBM on the human brain, we investigated alterations by repeated tPBM in vigilance performance and brain networks using electroencephalography (EEG) in healthy participants. Active and sham LED-based tPBM were administered to the right forehead of young participants twice a week for four weeks. The participants performed a psychomotor vigilance task (PVT) during each tPBM/sham experiment. A 64-electrode EEG system recorded electrophysiological signals from each participant during the first and last visits in the 4-week study. Topographical maps of EEG power enhanced by tPBM were statistically compared for the repeated tPBM effect. A new data-processing framework combining the group singular value decompensation (gSVD) with eLORETA was implemented to identify EEG brain networks. The reaction time of PVT in the tPBM-treated group was significantly improved over four weeks compared to that in the sham group. We observed acute increases in EEG delta and alpha powers during 10-min LED-tPBM while the participants performed the PVT task. We also found that theta, beta, and gamma EEG powers significantly increased globally after four weeks of LED-tPBM. Combining gSVD with eLORETA enabled us to identify EEG brain networks and the corresponding network power changes by repeated 4-week tPBM. This study clearly demonstrated that 4-week prefrontal LED-tPBM can neuromodulate several key EEG networks, implying a possible causal effect between modulated brain networks and improved psychomotor vigilance outcomes.
... No effect on rCBF was found in both studies. The same observation has been made using another CBF measurement technique, namely diffuse correlation spectroscopy (DCS) (Spera et al. 2021). Blood flow has also been investigated by the use of transcranial Doppler ultrasound (Salgado et al. 2015). ...
... (ii) All articles noted that tPBM applied to the frontal lobe appears to decrease the spectral density of slow oscillations in the δ -θ frequency range (Jahan et al. 2019;Wang et al. 2021;Yao et al. 2021;Zomorrodi et al. 2019). (iii) In contrast, all articles revealed that tPBM seems to increase the spectral density of neural oscillations in the α, β, γ frequency range (Shahdadian et al. 2022;Spera et al. 2021;Wang et al. 2019Wang et al. , 2021Wang et al. 2022b;Yao et al. 2021;Zomorrodi et al. 2019). (iv) All articles reported that the tPBM effects across the different frequency bands seemed to extend largely beyond the stimulation site: bilaterally, and from frontal to parietal, central and even occipital regions. ...
... About half of the studies used LEDs, while the other half used laser diodes. Eight studies used pulsed stimulation (pulse wave, PW); the others used continuous wave (CW), while two studies used both and compared the effect of the types of stimulation (Spera et al. 2021;Yao et al. 2021). Spera and colleagues (2021) found an effect of the PBM stimulation, but only when a continuous stimulation was applied, while Yao and colleagues (2021) reported an increased effect with increasing pulse frequency. ...
In recent years, transcranial photobiomodulation (tPBM) has been developing as a promising method to protect and repair brain tissues against damages. The aim of our systematic review is to examine the results available in the literature concerning the efficacy of tPBM in changing brain activity in humans, either in healthy individuals, or in patients with neurological diseases. Four databases were screened for references containing terms encompassing photobiomodulation, brain activity, brain imaging, and human. We also analysed the quality of the included studies using validated tools. Results in healthy subjects showed that even after a single session, tPBM can be effective in influencing brain activity. In particular, the different transcranial approaches - using a focal stimulation or helmet for global brain stimulation - seemed to act at both the vascular level by increasing regional cerebral blood flow (rCBF) and at the neural level by changing the activity of the neurons. In addition, studies also showed that even a focal stimulation was sufficient to induce a global change in functional connectivity across brain networks. Results in patients with neurological disease were sparser; nevertheless, they indicated that tPBM could improve rCBF and functional connectivity in several regions. Our systematic review also highlighted the heterogeneity in the methods and results generated, together with the need for more randomised controlled trials in patients with neurological diseases. In summary, tPBM could be a promising method to act on brain function, but more consistency is needed in order appreciate fully the underlying mechanisms and the precise outcomes.
