Biology subjects

Van Lankveld, H.

Publications and source records attributed to Van Lankveld, H..

9 recordsLinked to original sources

bioRxiv2026

Intranasal photobiomodulation: an energy efficient paradigm for cortical and subcortical stimulation

Previous studies have shown the hemodynamic response to transcranial photobiomodulation (tPBM) in localized cortical regions during and after forehead irradiation. However, it is unclear if tPBM can reach deeper regions such as subcortical tissue. It is also unclear whether the manner of regional neurovascular coupling predominantly studied using tPBM extends to all brain regions. As an alternative to forehead delivery, intranasal PBM (iPBM) uses the pathway of the cribriform plate, which is thin and directly leads to the orbitofrontal cortex, rather than the prefrontal cortex in the case of forehead PBM. Thus, it is possible that iPBM can stimulate the brain more efficiently (i.e. with less power). In this study, healthy young adults underwent different iPBM protocols differing in wavelength, frequency and irradiance. We utilized functional magnetic resonance imaging (fMRI) to quantify regional blood oxygenation (BOLD) and perfusion. We further model the neurovascular interactions underlying the fMRI response. We uncovered three distinct temporal signatures, varying by brain region. Specifically, a significant response in the thalamus was observed, with a time-locked BOLD response. Overall, iPBM was found to be associated with much higher efficiency at eliciting BOLD fMRI responses than its forehead (tPBM) counterpart. Lastly, in addition to the expected dose dependence, there were extensive sex differences in the fMRI response to iPBM, surpassing those observed for tPBM. Collectively, these findings highlight the feasibility and efficacy of iPBM and establish a foundation for personalizing PBM protocols for optimal outcomes.

neuroscience↗

bioRxiv2025

The fMRI response to transcranial photobiomodulation: the effect of wavelength, irradiance, frequency and skin tone on the BOLD and CBF response in healthy young adults

BackgroundTranscranial photobiomodulation (tPBM) utilizes near-infrared light to penetrate the skull to stimulate neural tissue. However, the in vivo physiological response and the factors influencing this response in the human brain have yet to be understood. MethodsIn this study, we utilize functional magnetic resonance imaging (fMRI) to evaluate the effect of tPBM on the blood-oxygenation (BOLD) and cerebral blood flow (CBF), while varying stimulation parameters such as wavelength, irradiance, and frequency. We further examine the influence of skin tone and sex. We further model the neurovascular interactions underlying the response. ResultsOur results show that the fMRI responses to tPBM is not restrained to the site of irradiation, but quickly spreads to distal sites. Certain regions display an fMRI response sustained after tPBM cessation. Importantly, the responses are dependent on biological and stimulation parameters. Lastly, biophysical modeling revealed a consistent neurovascular coupling-like behaviour underlying these responses. ConclusionEmpirical characterizations of dose dependence are critically important to brain stimulation methods in general but have yet to be demonstrated in most cases. This is the first tPBM study to do just that, establishing the foundation for precision medicine using tPBM, and sets a valuable precedent for the field of brain stimulation.

bioengineering↗

bioRxiv2025

Real-time spatial evolution of the fMRI response to photobiomodulation in the healthy human brain

Photobiomodulation (PBM) is a non-invasive therapeutic technique that uses low-level near-infrared light to influence mitochondrial metabolism and stimulate neural function. While PBM is increasingly used to improve cognitive and clinical outcomes, its in vivo physiological mechanisms in humans remain poorly characterized. In this study, we used BOLD-fMRI to investigate and quantify the temporal and spatial dynamics of transcranial PBM-induced brain activity in young, healthy adults, while incorporating multiple stimulation parameters (wavelength, irradiance, frequency) and transcranial delivery sites (right forehead and intranasal). A time-lagged correlation analysis revealed distinct spatiotemporal patterns of positive and negative BOLD responses that evolved over tens of seconds across both cortical surface and subcortical regions during stimulation. Notably, these effects propagated across brain regions that are potentially mediated by functional networks, were dose-dependent, and were modulated by individual skin tone. This work provides the first real-time, whole-brain mapping of PBM-induced hemodynamic changes in humans, offering new insights into dose-response characteristics and delivery-specific dynamics underlying PBM neurophysiology.

physiology↗

bioRxiv2025

Linking Electrophysiological Metrics to Oxidative Metabolism: Implications for EEG-fMRI Association

Resting-state functional magnetic resonance imaging (rs-fMRI) is widely used to study brain function, yet its biophysiological basis remains incompletely understood. Building on our recent work, we investigated how EEG activity and cerebral metabolic rate of oxygen (CMRO2) are related to one another, and how they jointly underpin rs-fMRI metrics. Using a multimodal dataset with macrovascular correction applied to all rs-fMRI metrics, we first examined associations between EEG metrics and CMRO2, then applied mediation analysis to evaluate how CMRO2 mediates EEG-fMRI associations. We found that bandlimited EEG theta and alphafractional power was significantly associated with CMRO2. Bandlimited EEG coherence was also associated with CMRO2 across all the bands. Bandlimited EEG fractional power and coherence were also significantly associated with cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in a manner that varied by frequency. EEG broadband temporal complexity was positively associated with CMRO2 and EEG coherence was negatively associated with OEF. Notably, there are pronounced sex differences in these relationships, which suggests that the biophysical underpinnings of rs-fMRI are sex dependent. Moreover, the baseline metabolic and hemodynamic variables did partially mediate EEG-fMRI associations, with CMRO2 serving as the primary mediator. However, most of the mediations are partial, highlighting the complex interplay among electrophysiological activity, oxidative metabolism, and hemodynamics. This study advances our understanding of the biophysical basis of rs-fMRI and provides a foundation for developing sex-specific diagnostic and therapeutic strategies for neurological disorders.

neuroscience↗

bioRxiv2025

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

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.

neuroscience↗

bioRxiv2025

Real-Time EEG Response to Pulsed Transcranial Photobiomodulation in Healthy Young Adults: Effects of Stimulation Parameters and Skin Tone

ObjectivesTranscranial photobiomodulation (tPBM) modulates cortical activity, but how specific stimulation parameters shape the electrophysiological response remains unclear. We tested whether pulsed forehead tPBM produces frequency band-specific EEG changes, whether pulsation frequency entrains endogenous oscillations, and whether wavelength, pulsation frequency, irradiance, sex, and skin tone significantly modulate the response. Materials and MethodsForty-six healthy young adults (24M/22F, 20-32 years) each completed four 12-minute EEG recordings (256-channel; PRE-DURING-POST, 4 min each) with pulsed NIR light delivered to the right forehead. The parameter space included two wavelengths (808 nm, 1064 nm), two pulsation frequencies (10 Hz, 40 Hz), and three irradiances (100, 150, 200 mW/cm2). Forehead skin tone (ITA) and sex were included as biological moderators. EEG band power (delta through gamma) was expressed as percent change from a pre-stimulus baseline. Spatiotemporal cluster-based permutation tests (10,000 permutations, FWER alpha=0.05) identified significant electrode clusters. Linear mixed-effects models with backward elimination and FDR correction (q=0.05) quantified parameter and biological contributions. ResultstPBM produced bilateral, bidirectional EEG changes: frontal gamma enhancement and posterior theta, alpha, and beta suppression, emerging gradually during stimulation and persisting post-stimulation. Wavelength qualitatively shaped the response: 808 nm drove broadband posterior suppression while 1064 nm selectively enhanced frontal gamma. Contrary to entrainment predictions, 10 Hz pulsation produced significantly larger gamma increases and theta reductions than 40 Hz. Sex was the most consistent biological modulator: females showed greater alpha suppression during stimulation and males showed greater posterior beta and gamma suppression. Irradiance and skin tone were not significant. ConclusionsPulsed forehead tPBM produces robust, parameter-dependent EEG changes that are not consistent with neural entrainment. Wavelength determines the character of the cortical response, pulsation frequency modulates its magnitude, potentially through photobiological rather than oscillatory mechanisms, and sex is a significant biological moderator. These findings contribute toward a human-specific foundation for informing optical tPBM parameter selection.

physiology↗

bioRxiv2025

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

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 Alzheimers 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.

physiology↗

bioRxiv2025

The Link to Oxidative Metabolism Varies across rs-fMRI Metrics: A Whole-Brain Assessment Using Macrovascular Correction

One of the major obstacles to the clinical application of resting-state functional magnetic resonance imaging (rs-fMRI) is the complex nature of its measurements, which limits interpretability. An approach to enhance the interpretability of the rs-fMRI metrics is to link them to more fundamental brain physiology, especially cerebral metabolism. Previous studies have established associations between glucose metabolism (CMRglu) and rs-fMRI measurements. In spite of this, oxidative metabolism (CMRO2) is more closely related to cerebral blood flow (CBF) and thus the BOLD signal, and its relationship with CMRglu is complex. Additionally, most currently published rs-fMRI metrics are uncorrected for macrovascular contribution, which may obscure the neuronal contributions. In this study, we measured resting CMRO2 (along with the oxygen extraction fraction, OEF and cerebral blood flow, CBF) using gas-free calibrated fMRI. We used linear mixed-effects (LME) models to examine associations between CMRO2 and various rs-fMRI metrics before and after macrovascular correction. We found that: 1) significant associations exist between CMRO2 and multiple rs-fMRI metrics, with the strongest association found for the global functional density (gFCD) and the weakest for seed-based functional connectivity (FC); 2) associations with rs-fMRI metrics also varied for OEF and CBF; 3) significant sex differences were observed in the above associations; 4) the use of macrovascular correction substantially strengthened the goodness fit of all LME models examined. This latter improvement further validates the use of macrovascular correction in rs-fMRI. These results provide a framework for linking rs-fMRI metrics to fundamental brain physiology, thus improving interpretability of rs-fMRI measurements. This is the first study to formally link whole-brain MRI-based baseline CMRO2 and rs-fMRI metrics, and helps to push the envelope for rs-fMRI in future clinical applications.

neuroscience↗

bioRxiv2024

Simulation-based dosimetry of transcranial and intranasal photobiomodulation of the human brain: the roles of wavelength, power density and skin colour

Photobiomodulation (PBM) is a novel technique that is actively studied for neuromodulation. However, despite the many in vivo studies, the stimulation protocols for PBM vary amongst studies, and the current understanding of neuromodulation via PBM is limited in terms of the extent of light penetration into the brain and its dosage dependence. Moreover, as near-infrared light can be absorbed by melanin in the skin, skin tone is a highly relevant but under-studied variable of interest. In this study, to address these gaps, we use Monte Carlo simulations (with MCX) of a single laser source for transcranial (tPBM) and intranasal (iPBM, nostril position) irradiated on a healthy human brain model. We investigate wavelengths of 670, 810 and 1064 nm in combination with light ("Caucasian"), medium ("Asian") and dark ("African") skin tones. Our simulations show that a maximum of 15% of the incidental energy for tPBM and 1% for iPBM reaches the cortex from the light source at the skin level. The rostral dorsal prefrontal cortex in tPBM and the ventromedial prefrontal cortex for iPBM accumulates the highest highest light energy, respectively for both wavelengths. Specifically, the 810 nm wavelength for tPBM and 1064 nm wavelength for iPBM produced the highest energy accumulation. Optical power density was found to be linearly correlated with energy. Moreover, we show that "Caucasian" skin allows the accumulation of higher light energy than other two skin colours. This study is the first to account for skin colour as a PBM dosing consideration, and provides evidence for hypothesis generation in in vivo studies of PBM.

biophysics↗