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Transcranial near-infrared stimulation (tNIRS) has been proposed as a tool to modulate cortical excitability. However, the underlying mechanisms are not clear where the heating effects on the brain tissue needs investigation due to increased near-infrared (NIR) absorption by water and fat. Moreover, the risk of localized heating of tissues (including the skin) during optical stimulation of the brain tissue is a concern. The challenge in estimating localized tissue heating is due to the light interaction with the tissues' constituents, which is dependent on the combination ratio of the scattering and absorption properties of the constituent. Here, apart from tissue heating that can modulate the cortical excitability ("photothermal effects"); the other mechanism reported in the literature is the stimulation of the mitochondria in the cells which are active in the adenosine triphosphate (ATP) synthesis. In the mitochondrial respiratory chain, Complex IV, also known as the cytochrome c oxidase (CCO), is the unit four with three copper atoms. The absorption peaks of CCO are in the visible (420-450 nm and 600-700 nm) and the near-infrared (760-980 nm) spectral regions, which have been shown to be promising for low-level light therapy (LLLT), also known as "photobiomodulation". While much higher CCO absorption peaks in the visible spectrum can be used for the photobiomodulation of the skin, 810 nm has been proposed for the non-invasive brain stimulation (using tNIRS) due to the optical window in the NIR spectral region. In this article, we applied a computational approach to delineate the "photothermal effects" from the "photobiomodulation", i.e., to estimate the amount of light absorbed individually by each chromophore in the brain tissue (with constant scattering) and the related tissue heating. Photon migration simulations were performed for motor cortex tNIRS based on a prior work that used a 500 mW cm - 2 light source placed on the scalp. We simulated photon migration at 630 nm and 700 nm (red spectral region) and 810 nm (near-infrared spectral region). We found a temperature increase in the scalp below 0.25 °C and a minimal temperature increase in the gray matter less than 0.04 °C at 810 nm. Similar heating was found for 630 nm and 700 nm used for LLLT, so photothermal effects are postulated to be unlikely in the brain tissue.

Computational Modeling of the Photon Transport, Tissue Heating, and Cytochrome C Oxidase Absorption during Transcranial Near-Infrared Stimulation