Consistent and real-time BOLD fMRI response to pulsed transcranial and intranasal photobiomodulation

Poster No:

50 

Submission Type:

Abstract Submission 

Authors:

Hannah Van Lankveld1, Joanna Chen1, Xiaole Zhong1, J. Jean Chen1

Institutions:

1University of Toronto, Rotman Research Institute, Toronto, Ontario

First Author:

Hannah Van Lankveld  
University of Toronto, Rotman Research Institute
Toronto, Ontario

Co-Author(s):

Joanna Chen  
University of Toronto, Rotman Research Institute
Toronto, Ontario
Xiaole Zhong  
University of Toronto, Rotman Research Institute
Toronto, Ontario
J. Jean Chen  
University of Toronto, Rotman Research Institute
Toronto, Ontario

Introduction:

Photobiomodulation (PBM) is the application of near-infrared (NIR) light to modulate brain activity by stimulating mitochondrial function and neurovascular coupling [1], [2]. PBM shows immense promise for enhancing cognition and aiding brain recovery for a range of neurodegenerative diseases [3]. To investigate the effects of PBM on brain activity and hemodynamics, various techniques, such as functional magnetic resonance imaging (fMRI) [4], NIR spectroscopy [5], and electroencephalography [2], have been used to map the PBM brain response, mainly by contrasting pre- and post-PBM. However, the real-time effect of PBM remains unclear. Using fMRI, this work is the first to examine the real-time brain response to pulsed transcranial PBM (tPBM) and intranasal PBM (iPBM) using BOLD fMRI. We examine whether tPBM and iPBM stimulate different brain regions, and what cognitive function may be related to these regions.

Methods:

Forty-one healthy adults (20–35 years), were recruited with an equal representation of sex and skin colour (three melanin groupings: light, intermediate and dark). Each participant underwent four 12-minute tPBM-fMRI, and four 12-minute iPBM-fMRI scans with varying optical power densities (tPBM: 100, 150, 200 mW/cm² | iPBM: 5, 7, 9 mW/cm²), wavelengths (808, 1064 nm), and frequencies (10, 40 Hz). Different subjects underwent PBM with different combinations of parameters in a randomized design. PBM was delivered via MRI-compatible lasers to the right forehead (tPBM), and the right nostril (iPBM) in sequence, marked with fiducial markers.

Data was collected on a Siemens Prisma 3T scanner using DE-pCASL (TR = 4.5 s; TE1/TE2 = 9.4/30 ms) with a [4-min-OFF, 4-min-ON, 4-min-OFF] stimulation timing protocol. Preprocessing was performed using a custom script that employed the FMRIB Software Library (FSL) for brain extraction, motion correction, slice timing and registration. As the hemodynamic response of PBM is unknown, FSL MELODIC was applied to data from all sessions for a model-independent response analysis that extracted 30 components. Components whose temporal primary eigenvalues significantly correlated with the stimulus were passed into a dual regression analysis to extract subject-specific regions of interest. Subsequently, all relevant regions within each subject were merged to generate an average per-subject time series.

Results:

For both tPBM and iPBM, BOLD activity increased in cortical grey matter. These regions, shown in Figure 1, consistently showed activation across all PBM stimulation modes, regardless of the specific stimulation parameters used. NeuroSynth decoding was performed on the positive ROIs [6], which revealed that the responses for both tPBM and iPBM are related to brain areas that integrate sensory, emotional, and cognitive information [7], implicating diverse cognitive processes such as attention, decision making and empathy, underscoring its central role in brain networks modulated by PBM stimulation [8].

To quantify the temporal dynamics of the spatial regions of interest (ROIs), the first eigenvector from all voxels showing this positive BOLD response across all subjects and protocols was used to capture the dominant flow of neural activity, as shown in Figure 2.

Conclusions:

This study is the first to use fMRI to demonstrate the real-time brain response to pulsed tPBM and iPBM. The two modes of stimulation elicited response in an overlapping set of regions, which could be due to the fact that both stimulated the frontal lobe. iPBM, although delivered at a much lower power density, elicited similar levels of BOLD response as tPBM. These regional specific real-time responses consolidate our understanding of the potential of PBM as a viable neurostimulation method. Further research will focus on dose dependence of these responses and their temporal evolution from the site of stimulation driving these effects.

Brain Stimulation:

Non-Invasive Stimulation Methods Other 1

Modeling and Analysis Methods:

Activation (eg. BOLD task-fMRI)

Novel Imaging Acquisition Methods:

BOLD fMRI 2

Keywords:

MRI
Other - Brain Stimulation; Photobiomodulation; Laser Stimulation

1|2Indicates the priority used for review
Supporting Image: OHBM-Abstract-1-figure-1.png
Supporting Image: OHBM-Abstract-1-figure-2.png
 

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Task-activation

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was this research conducted in the United States?

No

Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

Yes

Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

Not applicable

Please indicate which methods were used in your research:

Functional MRI
Other, Please specify  -   Photobiomodulation

For human MRI, what field strength scanner do you use?

3.0T

Which processing packages did you use for your study?

FSL

Provide references using APA citation style.

[1] Nairuz T, Sangwoo-Cho, Lee JH. Photobiomodulation Therapy on Brain: Pioneering an Innovative Approach to Revolutionize Cognitive Dynamics. Cells. 2024 Jun 3;13(11):966. doi: 10.3390/cells13110966. PMID: 38891098; PMCID: PMC11171912.

[2] Shahdadian S, Wang X, Liu H. Directed physiological networks in the human prefrontal cortex at rest and post transcranial photobiomodulation. Res Sq [Preprint]. 2023 Oct 6:rs.3.rs-3393702. doi: 10.21203/rs.3.rs-3393702/v1. Update in: Sci Rep. 2024 May 3;14(1):10242. doi: 10.1038/s41598-024-59879-7. PMID: 37886539; PMCID: PMC10602070.

[3] Hamblin, M. "Shining light on the head: Photobiomodulation for brain disorders," BBA Clin. Volume 6. December 2016.

[4] Dmochowski GM, Shereen AD, Berisha D, Dmochowski JP. Near-Infrared Light Increases Functional Connectivity with a Non-thermal Mechanism. Cereb Cortex Commun. 2020 Mar 19;1(1):tgaa004. doi: 10.1093/texcom/tgaa004. PMID: 34296085; PMCID: PMC8152883.

[5] Chan, Agnes S. et al. ‘Photobiomodulation Enhances Memory Processing in Older Adults with Mild Cognitive Impairment: A Functional Near-Infrared Spectroscopy Study’. 1 Jan. 2021 : 1471 – 1480.\

[6] Yarkoni T, Poldrack RA, Nichols TE, Van Essen DC, Wager TD. Large-scale automated synthesis of human functional neuroimaging data. Nat Methods. 2011 Jun 26;8(8):665-70. doi: 10.1038/nmeth.1635. PMID: 21706013; PMCID: PMC3146590.

[7] Gu X, Hof PR, Friston KJ, Fan J. Anterior insular cortex and emotional awareness. J Comp Neurol. 2013 Oct 15;521(15):3371-88. doi: 10.1002/cne.23368. PMID: 23749500; PMCID: PMC3999437.

[8] Namkung H, Kim SH, Sawa A. The Insula: An Underestimated Brain Area in Clinical Neuroscience, Psychiatry, and Neurology. Trends Neurosci. 2017 Apr;40(4):200-207. doi: 10.1016/j.tins.2017.02.002. Epub 2017 Mar 15. Erratum in: Trends Neurosci. 2018 Aug;41(8):551-554. doi: 10.1016/j.tins.2018.05.004. PMID: 28314446; PMCID: PMC5538352.

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