Significance: Major depressive disorder (MDD) affects over 40 million U.S. adults in their lifetime. Transcranial photobiomodulation (t-PBM) has been shown to be effective in treating MDD, but the current treatment dosage does not account for head and brain anatomical changes due to aging.

Aim: We study effective t-PBM dosage and its variations across age groups using state-of-the-art Monte Carlo simulations and age-dependent brain atlases ranging between 5 and 85 years of age.

Approach: Age-dependent brain models are derived from 18 MRI brain atlases. Two extracranial source positions, F3–F4 and Fp1–Fpz–Fp2 in the EEG 10–20 system, are simulated at five selected wavelengths and energy depositions at two MDD-relevant cortical regions—dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC)—are quantified.

Results: An overall decrease of energy deposition was found with increasing age. A strong negative correlation between the thickness of extracerebral tissues (ECT) and energy deposition was observed, suggesting that increasing ECT thickness over age is primarily responsible for reduced energy delivery. The F3–F4 position appears to be more efficient in reaching dlPFC compared to treating vmPFC via the Fp1–Fpz–Fp2 position.

Conclusions: Quantitative simulations revealed age-dependent light delivery across the lifespan of human brains, suggesting the need for personalized and age-adaptive t-PBM treatment planning.