The resting-state infra-slow oscillation (ISO) of the cerebral cortex reflects the neurophysiological state of the human brain. ISO results from distinct vasomotion with endogenic (E), neurogenic (N), and myogenic (M) frequency bands. Quantification of prefrontal ISO in cortical haemodynamics and metabolism in the resting human brain may facilitate the identification of objective features characteristic of certain brain disorders. The goal of this study was to explore and quantify the prefrontal ISO of the cortical concentrations of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome-c-oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics in all three E/N/M bands. Two-channel broadband near-infrared spectroscopy (2-bbNIRS) enabled measurements of the forehead of 26 healthy young participants in a resting state once a week for five weeks. After quantifying the ISO spectral amplitude (SA) and coherence at each E/N/M band, several key and statistically reliable metrics were obtained as key features: (1) SA of Δ[HbO] at all E/N/M bands, (2) SA of Δ[CCO] in the M band, (3) bilateral connectivity of hemodynamics and metabolism across the E and N bands, and (4) unilateral hemodynamic-metabolic coupling at both E and M bands. These features have promising potential to be developed as objective biomarkers for clinical applications in the future.

Billions of neurons in the human brain form neural networks with oscillation rhythms. Infra-slow oscillation (ISO) presents three main physiological sources: endogenic, neurogenic, and myogenic vasomotions. Having an in vivo methodology for the absolute quantification of ISO from the human brain can facilitate the detection of brain abnormalities in cerebral hemodynamic and metabolic activities. In this study, we introduced a novel measurement-plus-analysis framework for the non-invasive quantification of prefrontal ISO by (1) taking dual-channel broadband near infrared spectroscopy (bbNIRS) measurements from 12 healthy humans during a 6-min rest and 4-min post transcranial photobiomodulation (tPBM) and (2) performing wavelet transform coherence (WTC) analysis on the measured time series data. The WTC indexes (IC, between 0 and 1) enabled the assessment of ipsilateral hemodynamic-metabolic coherence and bilateral functional connectivity in each ISO band of the human prefrontal cortex. At rest, bilateral hemodynamic connectivity was consistent across the three ISO bands (IC ≅ 0.66), while bilateral metabolic connectivity was relatively weaker. For post-tPBM/sham comparison, our analyses revealed three key findings: 8-min, right-forehead, 1064-nm tPBM (1) enhanced the amplitude of metabolic oscillation bilaterally, (2) promoted the bilateral metabolic connectivity of neurogenic rhythm, and (3) made the main effect on endothelial cells, causing alteration of hemodynamic-metabolic coherence on each side of the prefrontal cortex.

Objective. Transcranial photobiomodulation (tPBM) has shown promising benefits, including cognitive improvement, in healthy humans and in patients with Alzheimer’s disease. In this study, we aimed to identify key cortical regions that present significant changes caused by tPBM in the electroencephalogram (EEG) oscillation powers and functional connectivity in the healthy human brain. Approach. A 64-channel EEG was recorded from 45 healthy participants during a 13-min period consisting of a 2-min baseline, 8-min tPBM/sham intervention, and 3-min recovery. After pre-processing and normalizing the EEG data at the five EEG rhythms, cluster-based permutation tests were performed for multiple comparisons of spectral power topographies, followed by graph-theory analysis (GTA) as a topological approach for quantification of brain connectivity metrics at global and nodal/cluster levels. Main results. EEG power enhancement was observed in clusters of channels over the frontoparietal regions in the alpha band and the centroparietal regions in the beta band. The global measures of the network revealed a reduction in synchronization, global efficiency, and small-worldness of beta band connectivity, implying an enhancement of brain network complexity. In addition, in the beta band, nodal graphical analysis demonstrated significant increases in local information integration and centrality over the frontal clusters, accompanied by a decrease in segregation over the bilateral frontal, left parietal, and left occipital regions. Significance. Frontal tPBM increased EEG alpha and beta powers in the frontal-central-parietal regions, enhanced the complexity of the global beta-wave brain network, and augmented local information flow and integration of beta oscillations across prefrontal cortical regions. This study sheds light on the potential link between electrophysiological effects and human cognitive improvement induced by tPBM.

Transcranial photobiomodulation (tPBM) is a noninvasive neuromodulation method that facilitates the improvement of human cognition. However, limited information is available in the literature on the wavelength-and site-specific effects of prefrontal tPBM. Moreover, 2-channel broadband near-infrared spectroscopy (2-bbNIRS) is a new approach for quantifying infra-slow oscillations (ISO; 0.005 to 0.2 Hz) of neurophysiological networks in the resting human brain in vivo.Aim: We aim to prove the hypothesis that the hemodynamic and metabolic activities of the resting prefrontal cortex are significantly modulated by tPBM and that the modulation is wavelength-and site-specific in different ISO bands.Approach: Noninvasive 8-min tPBM with an 800-or 850-nm laser or sham was delivered to either side of the forehead of 26 healthy young adults. A 2-bbNIRS unit was used to record prefrontal ISO activity 7 min before and after tPBM/sham. The measured time series were analyzed in the frequency domain to determine the coherence of hemodynamic and metabolic activities at each of the three ISO frequency bands. Sham-controlled coherence values represent tPBM-induced effects on neurophysiological networks.Results: Prefrontal tPBM by either wavelength and on either lateral side of the forehead (1) increased ipsilateral metabolic-hemodynamic coupling in the endogenic band and (2) desynchronized bilateral activity of metabolism in the neurogenic band and vascular smooth-muscle hemodynamics in the myogenic band. Site-specific effects of laser tPBM were also observed with significant enhancement of bilateral hemodynamic and metabolic connectivity by the right prefrontal 800-nm tPBM.Conclusions: Prefrontal tPBM can significantly modulate neurophysiological networks bilaterally and coupling unilaterally in the human prefrontal cortex. Such modulation effects are site-and wavelength-specific for each ISO band.

This study presented a theoretical or analytical approach to quantify how the signal-to-noise ratio (SNR) of a near infrared spectroscopy (NIRS) device influences the accuracy on calculated changes of oxy-hemoglobin (Δ[HbO]), deoxy-hemoglobin (Δ[HHb]), and oxidized cytochrome c oxidase (Δ[oxCCO]). In theory, all NIRS experimental measurements include variations due to thermal or electrical noise, drifts, and disturbance of the device. Since the computed concentration results are highly associated with device-driven variations, in this study, we applied the error propagation analysis to compute the variability or variance of Δ[HbO], Δ[HHb], and Δ[oxCCO] depending on the system SNR. The quantitative expressions of variance or standard deviations of changes in chromophore concentrations were derived based on the error propagation analysis and the modified Beer-Lambert law. In order to compare and confirm the derived variances versus those from the actual measurements, we conducted two sets of broadband NIRS (bbNIRS) measurements using a solid tissue phantom and the human forearm. A Monte Carlo framework was also executed to simulate the bbNIRS data under two physiological conditions for further confirmation of the theoretical analysis. Finally, the confirmed expression for error propagation was utilized for quantitative analyses to guide optimal selections of wavelength ranges and different wavelength combinations for minimal variances of Δ[HbO], Δ[HHb], and Δ[oxCCO] in actual experiments.