DOSE-DEPENDENT EFFECTS OF TRANSCRANIAL PHOTOBIOMODULATION ON BRAIN TEMPERATURE IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER: A SPECTROSCOPY STUDY

Background

Transcranial photobiomodulation (t-PBM) with nearinfrared (NIR) light penetrates the cerebral cortex and is absorbed by the mitochondrial enzyme cytochrome-C oxidase, stimulating the mitochondrial respiratory chain. t-PBM also significantly increases cerebral blood flow and oxygenation. Small-scale studies have reported that t-PBM may effectively treat Major Depressive Disorder (MDD). However, relationships between t-PBM dose and brain temperature effects are unclear. Therefore, possible excess brain warming during t-PBM administration is a concern and must be investigated. In this pilot study, we evaluated the dose-dependent brain temperature effects of t-PBM in subjects with MDD.

Methods

30 adult subjects (aged 18-65 years) meeting DSM-5 criteria for MDD, not treatment-resistant (0-2 failed antidepressants in the current episode), either unmedicated or on stable doses of antidepressants, with no other significant medical or psychiatric comorbidities, were enrolled. All subjects underwent three t-PBM sessions with different doses (peak irradiance; low: 50, medium: 300, high: 850 mW/cm2, low and medium doses were administered in continuous wave mode, high dose in pulsed wave mode) and sham treatment. H-MRS data: using a 3T Siemens Trio MRI scanner, single-voxel MRS was performed with a PRESS sequence (TE/TR =30ms/2s, dynamic averages = 32x4). A voxel with a volume of 30 mm × 30 mm × 15 mm was placed on the left prefrontal region. Brain temperature (°C) was derived by analyzing the 1H-MRS spectrum chemical shift differences between the water (~4.7 ppm) and N-acetyl aspartate (NAA) (~2.01 ppm) peaks, using jMRUI software’s HLSVD method and Zhu et al. formula: Tbrain (°C) = 36 - [103.8 × (ΔH2O−NAA - 2.6759)]. Pre-and post-irradiation temperature fluctuations for all conditions (active t-PBM and sham) were compared using a two-sample student-paired t-test [all data passed the normality test, Shapiro-Wilk test; W > 0.95, p-value > 0.23 (α=0.05)]. We also tested for potential differences in the pre-post variability (σ2) of brain temperature in each group using the respective sample sizes, mean, and standard deviation. Pearson correlation analyses were used to assess the absolute brain temperatures and [H2O-NAA] frequency difference association. An alpha value (α)=0.05 was considered the threshold for statistical significance. Statistical analyses were performed using GraphPad Prism 9.0.0.

Results

After quality control of the data, the following group numbers were available for both pre-and post-temperature estimations: Sham (n=10), Low (n=11), Medium (n=10), and High (n=8). We did not detect significant temperature differences for any t-PBM-active or sham groups post-irradiation (unpaired t-test; p-value range 0.105-0.781). We also tested for potential differences in the pre-post variability of brain temperature in each group. As for tPBM active groups, the lowest fluctuation (variance) was observed for the medium-dose (σ2=0.29), followed by the low-dose (σ2=0.47), and the highest fluctuation was for the highdose (σ2=0.67). Non-t-PBM sham condition showed the overall lowest fluctuation (σ2=0.11).

Conclusion

Our MRS thermometry results show no significant brain temperature elevations during the t-PBM application procedure. The brain temperature variations observed pre-and post-t-PBM sessions were not statistically significant. The lowest temperature variation was observed for the medium dose, while the highest was for the high dose. This study was part of the primary completion of the National Institute of Mental Health (NIMH) study (ClinicalTrials.gov Identifier: NCT04366258).

References

Iosifescu, D. V., Collins, K. A., Hurtado-Puerto, A., et al. Grant Report on the Transcranial near Infrared Radiation and Cerebral Blood Flow in Depression (TRIADE) Study. Photonics. 2023; 10(1), 90. https://doi.org/10.3390/photonics10010090 Weerasekera A, Coelho DRA, Ratai EM, et. al. Dose-dependent effects of transcranial photobiomodulation on brain temperature in patients with major depressive disorder: a spectroscopy study. Lasers Med Sci. 2024 Oct 7;39(1):249. doi: 10.1007/s10103-024-04198-