Research

Research papers and publications

PREPRINT2025

Real-time EEG response to pulsed transcranial photobiomodulation in healthy young adults: Effects of stimulation parameters and skin tone

Alicia Mathew, H. Van Lankveld, X. Z. Zhong, J. X. Chen, J. J. Chen

bioRxiv

Transcranial photobiomodulation (tPBM) relies on the photochemical stimulation of mitochondrial processes and has already demonstrated some ability to improve human cognition. However, it remains unclear how tPBM modulates neural oscillatory activity in real-time and how stimulation parameters and individual characteristics affect these responses. Capturing these dynamics is essential to understanding how tPBM's photochemical effects translate into effective neuromodulation, especially in diverse populations." Our study provides the first evidence of a cumulative increase in the power of neuro-electric oscillations in 46 healthy young adults with diverse skin tones who underwent 4 minutes of pulsed tPBM using varying laser parameters: two wavelengths (808/1064 nm), two pulsation frequencies (10/40 Hz), and three irradiances (100/150/200 mW/cm2). To capture "online" and "offline" effects, we analyzed minute-by-minute baseline-normalized frequency band power and used mixed-effects modeling to uncover significant predictors of EEG responses among tPBM parameters, skin tone, and sex. tPBM elicited frequency-band specific modulations in EEG power beginning near the stimulation site and propagating posteriorly over several minutes. Increases were cumulative with time, consistent with past fNIRS findings. They were also strongest and most sustained in beta/gamma bands, consistent with past findings of cognitive improvement. Significant parameter effects included stronger high-frequency responses at 808 nm and at 150 mW/cm2, wavelength-dependent frequency effects, larger responses in lighter skin, and parameter-specific sex differences. Both laser parameters and biological factors interact to shape tPBM's spatial and temporal neuromodulation profile and hence, parameter selection is crucial for achieving specific outcomes. Our findings uncover the manner in which tPBM induces neuronal changes, and contribute to a framework for creating more informed and personalized tPBM protocols.

PREPRINT2025

The link between steady-state EEG and rs-fMRI metrics in healthy young adults: the effect of macrovascular correction

X. Zhong, H. Van Lankveld, Alicia Mathew, J. J. Chen

bioRxiv

To improve the clinical utility of resting-state fMRI (rs-fMRI), enhancing its interpretability is paramount. Establishing links with electrophysiological activities remains the benchmark for understanding the neuronal basis of rs-fMRI signals. Existing research, while informative, suffers from inconsistencies and a limited scope of rs-fMRI metrics (e.g., seed-based functional connectivity). Phenotypic variables like sex and age are suspected to obscure reliable fMRI-EEG associations. A major contributing factor to these inconsistencies may be the neglect of macrovascular correction in rs-fMRI metrics. Given that macrovascular contributions can inflate rs-fMRI connectivity and power, they may lead to misleading fMRI-EEG associations that do not reflect genuine neuronal underpinnings. In this study, we addressed this by applying macrovascular correction and performing a systematic, inter-participant analysis of multiple rs-fMRI and EEG metrics. Our key findings demonstrate that: 1) Macrovascular correction enhances the relationship between EEG and rs-fMRI metrics and improves model fit in many instances; 2) sex significantly modulates EEG-fMRI associations; 3) EEG complexity is significantly associated with resting-state functional activity (RSFA). This research provides crucial insights into the interplay between rs-fMRI and EEG, ultimately improving the interpretability of rs-fMRI measurements and building upon our prior work linking fMRI and metabolism.

PREPRINT2025

Modulating cerebrospinal fluid dynamics using pulsed photobiomodulation: feasibility, parameter and skin-colour dependence

A. Motsenyat, X. Zhong, H. Van Lankveld, J. X. Chen, Alicia Mathew, J. J. Chen

bioRxiv

The use of photobiomodulation (PBM) to enhance brain health, specifically glymphatic drainage and thus neurotoxic waste clearance, may make it a promising therapeutic tool against neurodegenerative diseases such as Alzheimer's disease. This study investigates whether PBM can modulate cerebrospinal fluid (CSF) flow in 45 healthy young adults. We conducted forehead transcranial PBM (tPBM) and intranasal PBM (iPBM) at the nostril level, and measured CSF dynamics using blood-oxygenation level-dependent (BOLD) functional MRI (fMRI). Our data demonstrates 4 min of PBM-induced increases in CSF flow. Our data shows that (1) even a short PBM of 4 min can induce a change in CSF dynamics, in the form of an immediate increase in intracranial CSF volume and a reduction in CSF inflow; (2) skin melanin had a significant effect on the CSF response in tPBM, with lighter skin associated with higher responses; (3) both iPBM and tPBM displayed a dose-dependent effect on CSF dynamics in terms of a irradiance-wavelength interaction; (4) intranasal PBM (iPBM) can be used to produce a significant change in CSF dynamics that is equivalent to forehead transcranial PBM (tPBM) with a small fraction of the irradiance. The most likely explanation for the observed fMRI signal changes in CSF regions of interest for both tPBM and iPBM is an increased CSF outflow pressure due to PBM-induced vasodilation that transiently increases intracranial CSF volume and reduces net CSF inflow. This study establishes that PBM can modulate CSF flow in the healthy human brain in real time. This study also suggests that iPBM may be more efficient in CSF modulation due to the proximity to the olfactory system and the lack of melanin dependence. The influence of melanin on tPBM, the feasibility of iPBM and the dose dependence of both will require further investigation in healthy and patient populations.