Abstract
BACKGROUND: Brain waves synchronization with periodic external stimuli, such as flickering lights, auditory, or tactile stimuli, is known as entrainment. Flickering light-induced entrainment represents a new promising, fully non-invasive brain stimulation technique. Synchronization in the gamma range (between 30 and 150 Hz) is of particular therapeutic interest, as gamma brainwaves occur naturally when the brain is concentrated and involved in cognitive and executive function, and their alterations have been described in several neuropsychiatric conditions. While the effects of 40 Hz externally-induced neural entrainment have been extensively described, little is known about 60 Hz entrainment in humans. AIMS & OBJECTIVES: These studies focused on characterizing the cellular and electrophysiological responses of mouse and human brains to 60 Hz flickering white light. METHOD: The effects of 60 Hz flickering light (compared to sham light stimulation) were investigated in both adult C57BL6/J mice (5-day treatment, 2h per day) and healthy volunteers (30-min sessions, 3 weeks, 5 days/week). In mice, we applied immunohistochemistry, electrophysiology in the monocular deprivation model, and various behavioral paradigms to explore changes in cognition and depression-like traits. In humans, we tracked brain entrainment in an eight-channel EEG setup over 3 weeks of stimulation; recorded overall side effects, and measured C reactive protein (CRP) and cortisol levels in saliva. RESULTS: We show that selective light entrainment at 60 Hz in mice enables microglia-mediated remodelling of the perineuronal nets (PNN), extracellular matrix components that restrict synapse formation in adulthood. This reinstated juvenile-like plasticity in the monocular deprivation model. Moreover, 60 Hz augments cognition and has an anti-depressant-like effect reflected in reduced anxiety behavior and restored social interaction ability. Human studies confirmed that the 60 Hz flickering light induced neural entrainment across occipital, parietal, temporal, and frontal cortex. The signal was highly synchronous but declined significantly by day 19 compared to day 1, indicating neural habituation and potentially homeostatic plasticity. The stimulation was well tolerated and had only minor side effects such as sleepiness, headache, and dry eyes. CRP and cortisol levels were unchanged. DISCUSSION & CONCLUSIONS: 60 Hz flickering light induces strong neural entrainment and synchrony; the neural habituation observed suggests ongoing plastic changes. Given the role of 60 Hz in cognition, neuroplasticity, and neuropsychiatric disorders, this topic is of interest for potential applications in depression.