CNSPulse
W75

INTERMITTENT WHITE LIGHT AT 60 HZ AS A POTENTIAL NEUROSTIMULATION APPROACH FOR DEPRESSION: EFFECTS ON EEG ACTIVITY AND SAFETY IN HEALTHY HUMAN VOLUNTEERS

Maria Teresa Ferretti — MohammadAmin Alamalhoda1, Friederike Leesch1, Francesca Giovanetti1, Eoghan Dunne2, Giuseppina Pilloni3, Mark Caffrey1, Jack O’Keeffe1, Leigh Charvet3, Andre Brunoni4, Kallene Vidal5, Primavera Spagnolo6, Alessandro Venturino7 1Syntropic Medical, Austria, 2School of Medicine, University of Galway, 3New York University Grossman School of Medicine, 4 UT Southwestern Medical Center, 5Interdisciplinary Service of Neuromodulation, University of São Paulo, 6Brigham and Women's Hospital, Harvard Medical School, 7Institute of Science and Technology

2026 ASCP Annual Meeting

In addition to pharmacological treatments, non-invasive brain stimulation (NIBS) represents an option for the treatment of psychiatric diseases including major depressive disorder (MDD). Intermittent white light delivered at a specified frequency is currently being investigated as a novel NIBS intervention. We have previously shown that 60-Hz white light stimulation in mice induces brain entrainment, microglia-mediated remodelling of the perineuronal net, and reactivation of juvenile-like plasticity (ref. 1). These findings suggest a potential application in MDD and warrant further investigation in humans. This study was aimed to (1) characterize neural entrainment and synchrony induced by repeated 60-Hz flickering light using EEG, and (2) evaluate the safety and tolerability of this intervention in healthy volunteers. Ethical approval was obtained from the Lower Austria Ethical Commission (GS3-EK-4/908–2024). Participants (n=14) were randomized to receive either 15 daily sessions (30 minutes per session; five days per week for three weeks) of 60-Hz flickering white light (n=8) or sham stimulation, consisting of constant white light (n=6). Side effects were self-reported on a daily basis and a Likert-like questionnaire was administered to investigate the tolerability of the stimulation. Brain activity was tracked using an 8-channel EEG setup during stimulation sessions n. 1, 5, and 15. Data were analyzed with parametric (t-test and ANOVA) or non-parametric (Wilcoxon´s rank sum and Kruskal-Wallis) tests, according to normality. Ordinal questionnaire responses were evaluated using the Wilcoxon rank-sum test. Proportions were compared using Fisher’s exact test. Participants were young (sham: 25.5 ± 2.59 and active: 28.63 ± 6.37 years of age; p=0.6), balanced across sexes (sham: 50%, active: 62.5% female; p=1), mostly Caucasian (sham: 66.7%, active: 100%, p=0.16). Both constant and 60-Hz flickering light stimulation were well tolerated (‘the stimulation was overall tolerable’, average score sham:4.5 ± 0.55, active: 4.8 ± 0.41, p= 0.95). The majority of participants (sham: 83.3%, active: 87.5%, p=1) reported side effects, which were minor (such as sleepiness, headache, and dry eyes) and did not differ statistically across groups (total number of side effects: 20 in sham and 18 in active, p=1). EEG confirmed that 60-Hz flickering light induced neural entrainment across the occipital, parietal, temporal, and frontal cortex, with high synchrony. The entrainment signal showed a significant reduction by day 19 (last stimulation session) relative to day 1. This decline, accompanied by an emerging desynchronization, is consistent with neural habituation and may reflect homeostatic plasticity mechanisms.We conclude that repeated 60-Hz flickering white light induces robust neural entrainment and large-scale synchrony in the human brain, with evidence of adaptive plastic changes and no major safety concerns (ref. 2). Together with prior evidence that 60-Hz activity modulates emotional processing and cognition, these findings support further examination of this approach as a potential intervention for depressive disorders. Feasibility studies in patients are currently ongoing in the clinic (Lux study, NCT06922812) and at home (Neon study,