{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:04:18Z","timestamp":1791497058723,"version":"4.3.4"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Aleddra, Inc.","award":["SCRPD1P0361"],"award-info":[{"award-number":["SCRPD1P0361"]}]},{"DOI":"10.13039\/501100002836","name":"Chang Gung University","doi-asserted-by":"publisher","award":["BMRPE25"],"award-info":[{"award-number":["BMRPE25"]}],"id":[{"id":"10.13039\/501100002836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002836","name":"Chang Gung University","doi-asserted-by":"publisher","award":["URRPD1P0131"],"award-info":[{"award-number":["URRPD1P0131"]}],"id":[{"id":"10.13039\/501100002836","id-type":"DOI","asserted-by":"publisher"}]},{"award":["BMRPE25"],"award-info":[{"award-number":["BMRPE25"]}],"id":[{"id":"https:\/\/ror.org\/00d80zx46","id-type":"ROR","asserted-by":"publisher"}]},{"award":["URRPD1P0131"],"award-info":[{"award-number":["URRPD1P0131"]}],"id":[{"id":"https:\/\/ror.org\/00d80zx46","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Science and Technology Council","award":["NSTC-112-2410-H-182-030"],"award-info":[{"award-number":["NSTC-112-2410-H-182-030"]}]},{"name":"National Science and Technology Council","award":["NSTC-113-2314-B-182-064"],"award-info":[{"award-number":["NSTC-113-2314-B-182-064"]}]},{"name":"National Science and Technology Council","award":["NSTC-114-2314-B-182-016-MY3"],"award-info":[{"award-number":["NSTC-114-2314-B-182-016-MY3"]}]},{"name":"National Science and Technology Council","award":["NSTC-115-2637-B-182-001"],"award-info":[{"award-number":["NSTC-115-2637-B-182-001"]}]},{"award":["NSTC-112-2410-H-182-030"],"award-info":[{"award-number":["NSTC-112-2410-H-182-030"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NSTC-113-2314-B-182-064"],"award-info":[{"award-number":["NSTC-113-2314-B-182-064"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NSTC-114-2314-B-182-016-MY3"],"award-info":[{"award-number":["NSTC-114-2314-B-182-016-MY3"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NSTC-115-2637-B-182-001"],"award-info":[{"award-number":["NSTC-115-2637-B-182-001"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sci.","Brain Sciences"],"abstract":"<jats:p>Background: Forty-hertz sensory stimulation has emerged as a potential approach for modulating neural activity relevant to Alzheimer\u2019s disease. However, electrophysiological changes following non-flickering 40 Hz light stimulation in older adults remain unclear. This study investigated whether a single-session intervention of non-flickering 40 Hz light stimulation would be associated with increased resting-state 40 Hz oscillations in cognitively normal older adults. Methods: In this uncontrolled single-arm pilot study, 16 cognitively normal older adults underwent a 60 min session of non-flickering 40 Hz light stimulation. Resting-state EEG was recorded immediately before and after stimulation. Relative power within 38\u201342 Hz was analyzed across six predefined scalp regions and the whole-brain measure using one-tailed Wilcoxon signed-rank tests with Benjamini\u2013Hochberg false discovery rate (FDR) correction. Exploratory real-time EEG recordings during stimulation were available in 10 participants. Results: After FDR correction, resting-state 38\u201342 Hz relative power was higher post-stimulation in the central (FDR = 0.045, effect size = 0.555) and right temporal (FDR = 0.014, effect size = 0.724) regions. In the absolute-power sensitivity analysis, only the right temporal increase remained significant after FDR correction (FDR = 0.042). Exploratory during-stimulation analysis showed a nominally increased 38\u201342 Hz signal-to-noise ratio in the right temporal region (p = 0.026). One participant reported very mild fatigue; no other adverse responses were reported. Conclusions: This pilot study suggests regional increases in resting-state 38\u201342 Hz activity after non-flickering 40 Hz light stimulation, with additional absolute-power support for the right temporal finding. These findings remain preliminary given the uncontrolled design and small sample.<\/jats:p>","DOI":"10.3390\/brainsci16090976","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:57:34Z","timestamp":1789473454000},"page":"976","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Resting-State 40 Hz EEG Activity Before and After Single-Session Non-Flickering 40 Hz Light Stimulation in Cognitively Normal Older Adults: An Uncontrolled Pilot Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6654-9387","authenticated-orcid":false,"given":"Chia-Hsiung","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Occupational Therapy and Graduate Institute of Behavioral Sciences, Chang Gung University, Taoyuan 333323, Taiwan"},{"name":"Laboratory of Brain Imaging and Neural Dynamics (BIND Lab), Chang Gung University, Taoyuan 333323, Taiwan"},{"name":"Healthy Aging Research Center, Chang Gung University, Taoyuan 333323, Taiwan"},{"name":"Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsinjie","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Occupational Therapy and Graduate Institute of Behavioral Sciences, Chang Gung University, Taoyuan 333323, Taiwan"},{"name":"Laboratory of Brain Imaging and Neural Dynamics (BIND Lab), Chang Gung University, Taoyuan 333323, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.pharep.2014.09.004","article-title":"A review on Alzheimer\u2019s disease pathophysiology and its management: An update","volume":"67","author":"Kumar","year":"2015","journal-title":"Pharmacol. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer Disease: An Update on Pathobiology and Treatment Strategies","volume":"179","author":"Long","year":"2019","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"103290","DOI":"10.1016\/j.arr.2026.103290","article-title":"Mitochondrial homeostasis dysregulation: Potential mechanisms of Alzheimer\u2019s disease mediated by TDP-43","volume":"121","author":"Huang","year":"2026","journal-title":"Ageing Res. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e70115","DOI":"10.1002\/imo2.70115","article-title":"Strategies and mechanisms of precision genome engineering: From gene editing to genome writing","volume":"3","author":"Huang","year":"2026","journal-title":"iMetaOmics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nature20587","article-title":"Gamma frequency entrainment attenuates amyloid load and modifies microglia","volume":"540","author":"Iaccarino","year":"2016","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.neuron.2019.04.011","article-title":"Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection","volume":"102","author":"Adaikkan","year":"2019","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.tins.2019.11.001","article-title":"Gamma Entrainment: Impact on Neurocircuits, Glia, and Therapeutic Opportunities","volume":"43","author":"Adaikkan","year":"2020","journal-title":"Trends Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.cell.2019.02.014","article-title":"Multi-sensory Gamma Stimulation Ameliorates Alzheimer\u2019s-Associated Pathology and Improves Cognition","volume":"177","author":"Martorell","year":"2019","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1177\/13872877261429856","article-title":"Re-tuning the brain: The promise of 40 Hz sensory stimulation in Alzheimer\u2019s disease","volume":"111","author":"Scaramuzzi","year":"2026","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1177\/13872877251388664","article-title":"Therapeutic potential of 40 Hz flickering light stimulation in Alzheimer\u2019s disease: Mechanisms, evidence, and controversies","volume":"108","author":"Wang","year":"2025","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"653","DOI":"10.3233\/JAD-221238","article-title":"Safety, Feasibility, and Potential Clinical Efficacy of 40 Hz Invisible Spectral Flicker versus Placebo in Patients with Mild-to-Moderate Alzheimer\u2019s Disease: A Randomized, Placebo-Controlled, Double-Blinded, Pilot Study","volume":"92","author":"Agger","year":"2023","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chan, D., Suk, H.J., Jackson, B.L., Milman, N.P., Stark, D., Klerman, E.B., Kitchener, E., Fernandez Avalos, V.S., de Weck, G., and Banerjee, A. (2022). Gamma frequency sensory stimulation in mild probable Alzheimer\u2019s dementia patients: Results of feasibility and pilot studies. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0278412"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cimenser, A., Hempel, E., Travers, T., Strozewski, N., Martin, K., Malchano, Z., and Hajos, M. (2021). Sensory-Evoked 40-Hz Gamma Oscillation Improves Sleep and Daily Living Activities in Alzheimer\u2019s Disease Patients. Front. Syst. Neurosci., 15.","DOI":"10.3389\/fnsys.2021.746859"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3233\/JAD-230506","article-title":"Noninvasive Gamma Sensory Stimulation May Reduce White Matter and Myelin Loss in Alzheimer\u2019s Disease","volume":"97","author":"Da","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e12178","DOI":"10.1002\/trc2.12178","article-title":"A feasibility trial of gamma sensory flicker for patients with prodromal Alzheimer\u2019s disease","volume":"7","author":"He","year":"2021","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"ref_16","first-page":"6852303","article-title":"The Effect of 40-Hz Light Therapy on Amyloid Load in Patients with Prodromal and Clinical Alzheimer\u2019s Disease","volume":"2018","author":"Ismail","year":"2018","journal-title":"Int. J. Alzheimer\u2019s Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5425","DOI":"10.1007\/s00415-024-12486-y","article-title":"Exploring the impact of 40 Hz multi-luminaire light exposure in Alzheimer\u2019s dementia: Insights from a convenient sampling, non-randomized case-control study","volume":"271","author":"Li","year":"2024","journal-title":"J. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"335","DOI":"10.3233\/JAD-220081","article-title":"Novel Invisible Spectral Flicker Induces 40 Hz Neural Entrainment with Similar Spatial Distribution as 40 Hz Stroboscopic Light","volume":"88","author":"Agger","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29747","DOI":"10.1038\/s41598-024-75448-4","article-title":"Light-based gamma entrainment with novel invisible spectral flicker stimuli","volume":"14","author":"Hansen","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"121074","DOI":"10.1016\/j.neuroimage.2025.121074","article-title":"Transcranial vibration stimulation at 40 Hz induced neural activity and promoted the coupling of global brain activity and cerebrospinal fluid flow","volume":"308","author":"Kong","year":"2025","journal-title":"Neuroimage"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.clinph.2024.03.018","article-title":"40 Hz Repetitive auditory stimulation promotes corticospinal plasticity","volume":"162","author":"Pinardi","year":"2024","journal-title":"Clin. Neurophysiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.heares.2018.05.011","article-title":"Investigation of the 2f1-f2 and 2f2-f1 distortion product otoacoustic emissions using a computational model of the gerbil ear","volume":"365","author":"Wen","year":"2018","journal-title":"Hear. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3233\/JAD-231257","article-title":"Effects of 6-Month Combined Physical Exercise and Cognitive Training on Neuropsychological and Neurophysiological Function in Older Adults with Subjective Cognitive Decline: A Randomized Controlled Trial","volume":"100","author":"Cheng","year":"2024","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"193214","DOI":"10.1109\/ACCESS.2020.3033472","article-title":"Assessing the quality of wearable EEG systems using functional connectivity","volume":"8","author":"Mahdid","year":"2020","journal-title":"IEEE Access"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jneumeth.2003.10.009","article-title":"EEGLAB: An open source toolbox for analysis of single-trial EEG dynamics including independent component analysis","volume":"134","author":"Delorme","year":"2004","journal-title":"J. Neurosci. Methods"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1016\/j.clinph.2007.07.028","article-title":"EEG differences between eyes-closed and eyes-open resting conditions","volume":"118","author":"Barry","year":"2007","journal-title":"Clin. Neurophysiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e26746","DOI":"10.1002\/hbm.26746","article-title":"Brain state dynamics differ between eyes open and eyes closed rest","volume":"45","author":"Ingram","year":"2024","journal-title":"Hum. Brain Mapp."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e14158","DOI":"10.1111\/psyp.14158","article-title":"Longitudinal characterization of EEG power spectra during eyes open and eyes closed conditions in children","volume":"60","author":"Isler","year":"2023","journal-title":"Psychophysiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.neuroimage.2015.11.035","article-title":"Different coupling modes mediate cortical cross-frequency interactions","volume":"140","author":"Helfrich","year":"2016","journal-title":"Neuroimage"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.neuroimage.2015.05.044","article-title":"Measuring directionality between neuronal oscillations of different frequencies","volume":"118","author":"Jiang","year":"2015","journal-title":"Neuroimage"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/9\/976\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:38:11Z","timestamp":1789619891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/16\/9\/976"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["brainsci16090976"],"URL":"https:\/\/doi.org\/10.3390\/brainsci16090976","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}