ABSTRACT
Safe, noninvasive, and effective treatments for brain conditions are everyone's dream. Low-level light therapy (LLLT) based on the photobiomodulation (PBM) phenomenon has recently been adopted in practice, with solid scientific evidence. Optogenetics provides high spatiotemporal resolution to precisely switch on and off a particular circuitry in the brain. However, there are currently no human trials of optogenetics on the human brain. These two approaches-PBM and optogenetics-are promising photonic treatments that target the brain using completely different technologies. PBM is based on the mitochondrial reaction to the photons for up- or downregulation on the cytochrome c oxidase synthase in cellular respiration. It is safe, noninvasive, and good for long-term treatments, with wide applications using light wavelengths ranging from 650 nm to ≈1,100 nm, the red to near-infrared range. Optogenetics is based on the expression of engineered opsins on targeted tissues through viral vectors. The opsins are engineered to be sensors, actuators, or switches and could be precisely controlled by light wavelength ranging from 450 nm to ≈650 nm, the visible light range. The penetration of visible light is limited, and thus the photons cannot be applied directly outside the head without surgical means to create a physical window. PBM using near-infrared light could reach deeper tissues for light directly applied outside the head. Detailed scientific foundations and the state of the art for both technologies are reviewed. Ongoing developments are discussed to provide insight for future research and applications.
ABSTRACT
Transcranial infrared laser stimulation (TILS) at 1064 nm, 250 mW/cm2 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.
