Transcranial infrared light stimulation (TILS) has been shown to improve the performance of cognitive tests in adults with subjective memory complaints. Here we study whether long-term TILS benefits the cognitive functions of the elders. Through cognitive tests including card sorting test and delayed match-to-sample test, and functional near-infrared spectroscopy, we compared the cognitive tests performance and hemodynamics at the prefrontal cortex of healthy elders before and after two-to-four weeks of daily 10-mins TILS sessions. Results showed decreased hemodynamic responses after TILS, and greater cognitive enhancements in subjects receiving longer TILS. This may be explained by elevated efficiency of oxygen metabolism after TILS.
KEYWORDS: Brain, Monte Carlo methods, Tissues, Photon transport, Scattering, Absorption, Neurons, Energy efficiency, Magnetic resonance imaging, Computer simulations
Transcranial laser stimulation (TLS) is a neural type of photobiomodulation that has been shown beneficial effects on neurons. However, previous research in this field has used multiple wavelengths in the red to near-infrared range. It remains unclear which wavelength is optimal to stimulate the brain. In this study, Monte Carlo simulations are conducted to exposit the efficiencies of three representative wavelengths (660 nm, 810 nm and 1064 nm) in delivering photon energy into the brain. The results indicate that 1064 nm is the optimal, benefiting from its reduced tissue scattering.
Noninvasive transcranial photobiomodulation (tPBM) with a 1064-nm laser has been reported to improve human performance on cognitive tasks as well as locally upregulate cerebral oxygen metabolism and hemodynamics. However, it is unknown whether 1064-nm tPBM also modulates electrophysiology, and specifically neural oscillations, in the human brain. The hypothesis guiding our study is that applying 1064-nm tPBM of the right prefrontal cortex enhances neurophysiological rhythms at specific frequency bands in the human brain under resting conditions. To test this hypothesis, we recorded the 64-channel scalp electroencephalogram (EEG) before, during, and after the application of 11 min of 4-cm-diameter tPBM (CW 1064-nm laser with 162 mW / cm2 and 107 J / cm2) to the right forehead of human subjects (n = 20) using a within-subject, sham-controlled design. Time-resolved scalp topographies of EEG power at five frequency bands were computed to examine the tPBM-induced EEG power changes across the scalp. The results show time-dependent, significant increases of EEG spectral powers at the alpha (8 to 13 Hz) and beta (13 to 30 Hz) bands at broad scalp regions, exhibiting a front-to-back pattern. The findings provide the first sham-controlled topographic mapping that tPBM increases the strength of electrophysiological oscillations (alpha and beta bands) while also shedding light on the mechanisms of tPBM in the human brain.
KEYWORDS: Brain, Electroencephalography, Infrared lasers, In vivo imaging, Picture Archiving and Communication System, Cognition, Modulation, Data processing, Statistical analysis
Transcranial infrared laser stimulation (TILS) refers to the use of infrared laser to photobiomodulate the human brain, which has been reported beneficial in enhancing human cognition. We previously investigated TILS-induced electrophysiological effects and observed increases of power density in alpha wave oscillation. However, clear association between the brain wave alteration and improvement of neural cognition is limited. Phase–amplitude coupling (PAC) is a recently proposed neural mechanism for coordinating information processing across brain regions. In this study, we wish to examine if TILS would create any enhanced PAC at particular frequency bands in particular brain regions. A 64-channel electroencephalography (EEG) system was employed to determine placebo-controlled, electrophysiological activities from 19 healthy human participants before, during and after TILS. After a 2-minute baseline, we applied a 1064-nm laser with a total power of 3.5 W on the right forehead of each human participant for 8 minutes, followed by a 3-minute recovery period. An EEG processing package (Brainstorm) was used to perform cross-frequency PAC analysis for each participant’s measurement, followed by group-level, paired T-tests between the placebo and TILS conditions. The statistical results showed that TILS induced significant inter-cerebral PAC among several brain oscillations, specifically (1) slow-delta (0.5-1 Hz) activity modulating both alpha band (8-11 Hz) and high gamma band (70-85 Hz) activities, and (2) alpha band (8-11 Hz) modulating high gamma band (70-85 Hz) activity. All of these results suggest that TILS is able to enhance thalamocortical, cortical-hippocampal-cortical, and hippocampal-thalamic activity, all of which lead to enhancement of human cognition.
Transcranial infrared laser stimulation (TILS) has shown effectiveness in improving human cognition and was investigated using broadband near-infrared spectroscopy (bb-NIRS) in our previous study, but the effect of laser heating on the actual bb-NIRS measurements was not investigated. To address this potential confounding factor, 11 human participants were studied. First, we measured time-dependent temperature increases on forehead skin using clinical-grade thermometers following the TILS experimental protocol used in our previous study. Second, a subject-averaged, time-dependent temperature alteration curve was obtained, based on which a heat generator was controlled to induce the same temperature increase at the same forehead location that TILS was delivered on each participant. Third, the same bb-NIRS system was employed to monitor hemodynamic and metabolic changes of forehead tissue near the thermal stimulation site before, during, and after the heat stimulation. The results showed that cytochrome-c-oxidase of forehead tissue was not significantly modified by this heat stimulation. Significant differences in oxyhemoglobin, total hemoglobin, and differential hemoglobin concentrations were observed during the heat stimulation period versus the laser stimulation. The study demonstrated a transient hemodynamic effect of heat-based stimulation distinct to that of TILS. We concluded that the observed effects of TILS on cerebral hemodynamics and metabolism are not induced by heating the skin.
Transcranial infrared laser stimulation (TILS) is a non-destructive and non-thermal photobiomodulation therapy or process on the human brain; TILS uses infrared light from lasers or LEDs and has gained increased recognition for its beneficial effects on a variety of neurological and psychological conditions. While the mechanism of TILS has been assumed to stem from cytochrome-c-oxidase (CCO), which is the last enzyme in the electron transportation chain and is the primary photoacceptor, no literature is found to report electrophysiological response to TILS. In this study, a 64-channel electroencephalography (EEG) system was employed to monitor electrophysiological activities from 15 healthy human participants before, during and after TILS. A placebo experimental protocol was also applied for rigorous comparison. After recording a 3-minute baseline, we applied a 1064-nm laser with a power of 3.5W on the right forehead of each human participant for 8 minutes, followed by a 5-minute recovery period. In 64-channel EEG data analysis, we utilized several methods (root mean square, principal component analysis followed by independent component analysis, permutation conditional mutual information, and time-frequency wavelet analysis) to reveal differences in electrophysiological response to TILS between the stimulated versus placebo group. The analyzed results were further investigated using general linear model and paired t-test to reveal statistically meaningful responses induced by TILS. Moreover, this study will provide spatial mapping of human electrophysiological and possibly neural network responses to TILS for first time, indicating the potential of EEG to be an effective method for monitoring neurological improvement induced by TILS.
KEYWORDS: Oxygen, Infrared lasers, Hemodynamics, Near infrared spectroscopy, In vivo imaging, Infrared radiation, Light emitting diodes, Nondestructive evaluation, Brain, Electron transport
Transcranial infrared laser stimulation (TILS) uses infrared light (lasers or LEDs) for nondestructive and non-thermal photobiomodulation on the human brain. Although TILS has shown its beneficial effects to a variety of neurological and psychological conditions, its physiological mechanism remains unknown. Cytochrome-c-oxidase (CCO), the last enzyme in the electron transportation chain, is proposed to be the primary photoacceptor of this infrared laser. In this study, we wish to validate this proposed mechanism. We applied 8 minutes in vivo TILS on the right forehead of 11 human participants with a 1064-nm laser. Broad-band near infrared spectroscopy (bb-NIRS) from 740-900nm was also employed near the TILS site to monitor hemodynamic and metabolic responses during the stimulation and 5-minute recovery period. For rigorous comparison, we also performed similar 8-min bb-NIR measurements under placebo conditions. A multi-linear regression analysis based on the modified Beer-Lambert law was performed to estimate concentration changes of oxy-hemoglobin (Δ[HbO]), deoxy-hemoglobin (Δ[Hb]), and cytochrome-c-oxidase (Δ[CCO]). We found that TILS induced significant increases of [CCO], [HbO] and a decrease of [Hb] with dose-dependent manner as compared with placebo treatments. Furthermore, strong linear relationships or interplays between [CCO] versus [HbO] and [CCO] versus [Hb] induced by TILS were observed in vivo for the first time. These relationships have clearly revealed close coupling/relationship between the hemodynamic oxygen supply and blood volume versus up-regulation of CCO induced by photobiomodulation. Our results demonstrate the tremendous potential of bb-NIRS as a non-invasive in vivo means to study photobiomodulation mechanisms and perform treatment evaluations of TILS.
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