Transcranial infrared laser stimulation (TILS) is a noninvasive form of brain photobiomulation. Cytochrome-c-oxidase (CCO), the terminal enzyme in the mitochondrial electron transport chain, is hypothesized to be the primary intracellular photoacceptor. We hypothesized that TILS up-regulates cerebral CCO and causes hemodynamic changes. We delivered 1064-nm laser stimulation to the forehead of healthy participants ( n = 11), while broadband near-infrared spectroscopy was utilized to acquire light reflectance from the TILS-treated cortical region before, during, and after TILS. Placebo experiments were also performed for accurate comparison. Time course of spectroscopic readings were analyzed and fitted to the modified Beer-Lambert law. With respect to the placebo readings, we observed (1) significant increases in cerebral concentrations of oxidized CCO (Δ[CCO]; >0.08 µM; p < 0.01), oxygenated hemoglobin (Δ[HbO]; >0.8 µM; p < 0.01), and total hemoglobin (Δ[HbT]; >0.5 µM; p < 0.01) during and after TILS, and (2) linear interplays between Δ[CCO] versus Δ[HbO] and between Δ[CCO] versus Δ[HbT]. Ratios of Δ[CCO]/Δ[HbO] and Δ[CCO]/Δ[HbT] were introduced as TILS-induced metabolic-hemodynamic coupling indices to quantify the coupling strength between TILS-enhanced cerebral metabolism and blood oxygen supply. This study provides the first demonstration that TILS causes up-regulation of oxidized CCO in the human brain, and contributes important insight into the physiological mechanisms.

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.

BACKGROUND AND PURPOSE: Magnetoencephalography is sensitive to functional connectivity changes associated with concussion. However, the directional influences between functionally related regions remain unexplored. In this study, we therefore evaluated concussion-related magnetoencephalography-based effective connectivity changes within resting-state default mode network regions. MATERIALS AND METHODS:Resting-state magnetoencephalography was acquired for 8 high school football players with concussion at 3 time points (preseason, postconcussion, postseason), as well as 8 high school football players without concussion and 8 age-matched controls at 2 time points (preseason, postseason). Time-series from the default mode network regions were extracted, and effective connectivity between them was computed for 5 different frequency bands. The default mode network regions were grouped into anterior and posterior default mode networks. The combined posterior-to-anterior and anterior-to-posterior effective connectivity values were averaged to generate 2 sets of values for each subject. The effective connectivity values were compared using a repeated measures ANOVA across time points for the concussed, nonconcussed, and control groups, separately.RESULTS: A significant increase in posterior-to-anterior effective connectivity from preseason to postconcussion (corrected P value ¼ .013) and a significant decrease in posterior-to-anterior effective connectivity from postconcussion to postseason (corrected P value ¼ .028) were observed in the concussed group. Changes in effective connectivity were only significant within the delta band. Anterior-to-posterior connectivity demonstrated no significant change. Effective connectivity in the nonconcussed group and controls did not show significant differences.