Transcranial infrared laser stimulation (TILS) at 1064 nm, 250 mW/cm has been proven safe and effective for increasing neurocognitive functions in young adults in controlled studies using photobiomodulation of the right prefrontal cortex. The objective of this pilot study was to determine whether there is any effect from TILS on neurocognitive function in older adults with subjective memory complaint at risk for cognitive decline (e.g., increased carotid artery intima-media thickness or mild traumatic brain injury). We investigated the cognitive effects of TILS in older adults (ages 49-90, n = 12) using prefrontal cortex measures of attention (psychomotor vigilance task (PVT)) and memory (delayed match to sample (DMS)), carotid artery intima-media thickness (measured by ultrasound), and evaluated the potential neural mechanisms mediating the cognitive effects of TILS using exploratory brain studies of electroencephalography (EEG, n = 6) and functional magnetic resonance imaging (fMRI, n = 6). Cognitive performance, age, and carotid artery intima-media thickness were highly correlated, but all participants improved in all cognitive measures after TILS treatments. Baseline vs. chronic (five weekly sessions, 8 min each) comparisons of mean cognitive scores all showed improvements, significant for PVT reaction time (p < 0.001), PVT lapses (p < 0.001), and DMS correct responses (p < 0.05). The neural studies also showed for the first time that TILS increases resting-state EEG alpha, beta, and gamma power and promotes more efficient prefrontal blood-oxygen-level-dependent (BOLD)-fMRI response. Importantly, no adverse effects were found. These preliminary findings support the use of TILS for larger randomized clinical trials with this non-invasive approach to augment neurocognitive function in older people to combat aging-related and vascular disease-related cognitive decline.

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Background: Transcranial laser stimulation is a novel method of noninvasive brain stimulation found safe and effective for improving prefrontal cortex neurocognitive functions in healthy young adults. This method is different from electric and magnetic stimulation because it causes the photonic oxidation of cytochrome-c-oxidase, the rate-limiting enzyme for oxygen consumption and the major intracellular acceptor of photons from near-infrared light. This photobiomodulation effect promotes mitochondrial respiration, cerebrovascular oxygenation and neurocognitive function. Pilot studies suggest that transcranial photobiomodulation may also induce beneficial effects in aging individuals. Objectives: Randomized, sham-controlled study to test photobiomodulation effects caused by laser stimulation on cytochrome-c-oxidase oxidation and hemoglobin oxygenation in the prefrontal cortex of 68 healthy younger and older adults, ages 18e85. Methods: Broadband near-infrared spectroscopy was used for the noninvasive quantification of bilateral cortical changes in oxidized cytochrome-c-oxidase and hemoglobin oxygenation before, during and after 1064-nm wavelength laser (IR-A laser, area: 13.6 cm 2 , power density: 250 mW/cm 2 ) or sham stimulation of the right anterior prefrontal cortex (Brodmann Area 10). Results: As compared to sham control, there was a significant laser-induced increase in oxidized cytochrome-c-oxidase during laser stimulation, followed by a significant post-stimulation increase in oxygenated hemoglobin and a decrease in deoxygenated hemoglobin. Furthermore, there was a greater laser-induced effect on cytochrome-c-oxidase with increasing age, while laser-induced effects on cerebral hemodynamics decreased with increasing age. No adverse laser effects were found. Conclusion:The findings support the use of transcranial photobiomodulation for cerebral oxygenation and alleviation of age-related decline in mitochondrial respiration. They justify further research on its therapeutic potential in neurologic and psychiatric diseases.

Transcranial infrared laser stimulation (TILS) is a novel, safe, non-invasive method of brain photobiomodulation. Laser stimulation of the human prefrontal cortex causes cognitive enhancement. To investigate the hemodynamic effects in prefrontal cortex by which this cognitive enhancement occurs, we used functional near-infrared spectroscopy (fNIRS), which is a safe, non-invasive method of monitoring hemodynamics. We measured concentration changes in oxygenated and deoxygenated hemoglobin, total hemoglobin and differential effects in 18 healthy adults during sustained attention and working memory performance, before and after laser of the right prefrontal cortex. We also measured 16 sham controls without photobiomodulation. fNIRS revealed large effects on prefrontal oxygenation during cognitive enhancement post-laser and provided the first demonstration that cognitive enhancement by transcranial photobiomodulation is associated with cerebrovascular oxygenation of the prefrontal cortex. Sham control data served to rule out that the laser effects were due to pre-post task repetition or other non-specific effects. A laser-fNIRS combination may be useful to stimulate and monitor cerebrovascular oxygenation associated with neurocognitive enhancement in healthy individuals and in those with prefrontal hypometabolism, such as in cognitive aging, dementia and many neuropsychiatric disorders.

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