{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T02:02:51Z","timestamp":1777341771699,"version":"3.51.4"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Child Adolesc. Psychiatry"],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Small pilot studies have indicated that transcranial photobiomodulation (tPBM) may help alleviate symptoms of neurological conditions like depression, traumatic brain injury and Autism Spectrum Disorder (ASD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine the effect of tPBM on the behavioral symptoms of ASD and brain electrophysiology in children aged 2\u20137.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted an open label, one-arm study with 23 participants, aged 2\u20137, previously diagnosed with ASD. We delivered non-invasively to all participants pulses of near-infrared light (wavelength 850\u2005nm, pulse 40\u2005Hz) to cortical nodes of Default Mode Network, Broca and Wernicke areas, and occipital lobe of the brain, twice weekly for 10 weeks. The tPBM was delivered using an investigational medical device designed for this purpose. Changes in ASD symptoms were measured using pre- and post-intervention scores on the Childhood Autism Rating Scale (CARS-2, 2nd Edition). We collected electroencephalogram (EEG) data after each treatment session from all children who tolerated wearing the EEG cap to monitor changes in brain activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The intervention resulted in a significant 7-point reduction in average CARS-2 scores (<jats:italic>t<\/jats:italic>\u2009=\u200910.23, <jats:italic>p<\/jats:italic>\u2009&amp;lt;\u2009.0001), along with decreased delta power and increased gamma and beta power in EEG readings. The increase in gamma power was statistically significant [<jats:italic>t<\/jats:italic>(14)\u2009=\u20092.30, <jats:italic>p<\/jats:italic>\u2009=\u20090.047]. Changes in EEG power were significantly correlated with the number of sessions (delta: <jats:italic>r<\/jats:italic>(192)\u2009=\u2009\u22120.18, <jats:italic>p<\/jats:italic>\u2009=\u2009.013; gamma: <jats:italic>r<\/jats:italic>(192)\u2009=\u2009.19, <jats:italic>p<\/jats:italic>\u2009=\u2009.007; beta: <jats:italic>r<\/jats:italic>(192)\u2009=\u2009.15, <jats:italic>p<\/jats:italic>\u2009=\u2009.04). Improvements in CARS-2 scores were negatively correlated with changes in delta and beta power (delta: <jats:italic>r<\/jats:italic>(15)\u2009=\u2009\u2212.59, <jats:italic>p<\/jats:italic>\u2009=\u2009.020; beta: <jats:italic>r<\/jats:italic>(15)\u2009=\u2009\u2212.54, <jats:italic>p<\/jats:italic>\u2009=\u2009.037). No moderate or severe side effects were reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study supports the potential of tPBM as a safe and effective treatment for ASD, and it suggests that EEG measurements may serve as a useful biomarker for future research.\n<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p><jats:uri>https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04660552<\/jats:uri><\/jats:p><\/jats:sec>","DOI":"10.3389\/frcha.2025.1477839","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T06:59:53Z","timestamp":1738133993000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcranial photobiomodulation for reducing symptoms of autism spectrum disorder and modulating brain electrophysiology in children aged 2\u20137: an open label study"],"prefix":"10.3389","volume":"4","author":[{"given":"Yuli","family":"Fradkin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaquin A.","family":"Anguera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander J.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"De Taboada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenia","family":"Steingold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s10567-012-0119-6","article-title":"Parent and family impact of autism spectrum disorders: a review and proposed model for intervention evaluation","volume":"15","author":"Karst","year":"2012","journal-title":"Clin Child Fam Psychol Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"101502","DOI":"10.1016\/j.rasd.2019.101502","article-title":"The lifetime social cost of autism: 1990\u20132029","volume":"72","author":"Cakir","year":"2020","journal-title":"Res Autism Spectr Disord"},{"key":"B3","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1016\/j.jaac.2018.11.017","article-title":"Recurrence risk of autism in siblings and cousins: a multinational, population-based study","volume":"58","author":"Hansen","year":"2019","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1001\/jama.2014.4144","article-title":"The familial risk of autism","volume":"311","author":"Sandin","year":"2014","journal-title":"JAMA"},{"key":"B5","doi-asserted-by":"publisher","first-page":"100829","DOI":"10.1016\/j.spen.2020.100829","article-title":"Mitochondrial dysfunction in autism spectrum disorder: unique abnormalities and targeted treatments","volume":"35","author":"Frye","year":"2020","journal-title":"Semin Pediatr Neurol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e360","DOI":"10.1038\/tp.2014.4","article-title":"Environmental toxicants and autism spectrum disorders: a systematic review","volume":"4","author":"Rossignol","year":"2014","journal-title":"Transl Psychiatry"},{"key":"B7","doi-asserted-by":"publisher","first-page":"114561","DOI":"10.1016\/j.ecoenv.2023.114561","article-title":"The role of environmental trace element toxicants on autism: a medical biogeochemistry perspective","volume":"251","author":"Awadh","year":"2023","journal-title":"Ecotoxicol Environ Saf"},{"key":"B8","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/978-3-030-30402-7_5","article-title":"Maternal prenatal exposures in pregnancy and autism spectrum disorder: an insight into the epigenetics of drugs and diet as key environmental influences","volume":"24","author":"Bastaki","year":"2020","journal-title":"Adv Neurobiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1017\/S1740925X12000142","article-title":"Evidence of microglial activation in autism and its possible role in brain underconnectivity","volume":"7","author":"Rodriguez","year":"2011","journal-title":"Neuron Glia Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1159\/000398791","article-title":"Role of microglia in autism: recent advances","volume":"37","author":"Takano","year":"2015","journal-title":"Dev Neurosci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"246","DOI":"10.9758\/cpn.2018.16.3.246","article-title":"Microglia and autism spectrum disorder: overview of current evidence and novel immunomodulatory treatment options","volume":"16","author":"Kim","year":"2018","journal-title":"Clin Psychopharmacol Neurosci"},{"key":"B12","first-page":"21","article-title":"Mitochondrial dysfunction: a key player in the pathogenesis of autism Spectrum disorders and Alzheimer\u2019s disease","volume-title":"Autism Spectrum Disorder and Alzheimer\u2019s Disease: Advances in Research","author":"Farhana","year":"2022"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2389","DOI":"10.1001\/jama.2010.1706","article-title":"Mitochondrial dysfunction in autism","volume":"304","author":"Giulivi","year":"2010","journal-title":"JAMA"},{"key":"B14","doi-asserted-by":"publisher","first-page":"41R","DOI":"10.1203\/PDR.0b013e318212f16b","article-title":"Mitochondrial dysfunction can connect the diverse medical symptoms associated with autism spectrum disorders","volume":"69","author":"Frye","year":"2011","journal-title":"Pediatr Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1016\/j.neubiorev.2012.02.007","article-title":"Autism as a neural systems disorder: a theory of frontal-posterior underconnectivity","volume":"36","author":"Just","year":"2012","journal-title":"Neurosci Biobehav Rev"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep26527","article-title":"Alteration of functional connectivity in autism spectrum disorder: effect of age and anatomical distance","volume":"6","author":"Long","year":"2016","journal-title":"Sci Rep"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e0175870","DOI":"10.1371\/journal.pone.0175870.","article-title":"Is functional brain connectivity atypical in autism? A systematic review of EEG and MEG studies","volume":"12","author":"O\u2019Reilly","year":"2017","journal-title":"PLoS One"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s42003-021-02572-6","article-title":"Connectivity alterations in autism reflect functional idiosyncrasy","volume":"4","author":"Benkarim","year":"2021","journal-title":"Commun Biol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1038\/s41401-022-00879-6","article-title":"Mitochondrial-derived damage-associated molecular patterns amplify neuroinflammation in neurodegenerative diseases","volume":"43","author":"Lin","year":"2022","journal-title":"Acta Pharmacol Sin"},{"key":"B20","doi-asserted-by":"publisher","first-page":"614","DOI":"10.3389\/fpsyt.2020.00614","article-title":"A review of default mode network connectivity and its association with social cognition in adolescents with autism spectrum disorder and early-onset psychosis","volume":"11","author":"Nair","year":"2020","journal-title":"Front Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.neubiorev.2008.09.002","article-title":"Default-mode brain dysfunction in mental disorders: a systematic review","volume":"33","author":"Broyd","year":"2009","journal-title":"Neurosci Biobehav Rev"},{"key":"B22","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1016\/j.bpsc.2017.04.004","article-title":"The default mode network in autism","volume":"2","author":"Padmanabhan","year":"2017","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging"},{"key":"B23","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.bbacli.2016.09.002","article-title":"Shining light on the head: photobiomodulation for brain disorders","volume":"6","author":"Hamblin","year":"2016","journal-title":"BBA Clin"},{"key":"B24","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1007\/s10439-011-0454-7","article-title":"The nuts and bolts of low-level laser (light) therapy","volume":"40","author":"Chung","year":"2012","journal-title":"Ann Biomed Eng"},{"key":"B25","doi-asserted-by":"publisher","first-page":"602","DOI":"10.2203\/dose-response.11-009.Hamblin","article-title":"Biphasic dose response in low level light therapy","volume":"9","author":"Huang","year":"2011","journal-title":"Dose Response"},{"key":"B26","doi-asserted-by":"publisher","first-page":"337","DOI":"10.3934\/biophy.2017.3.337","article-title":"Mechanisms and applications of the anti-inflammatory effects of photobiomodulation","volume":"4","author":"Hamblin","year":"2017","journal-title":"AIMS Biophys"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-019-42693-x","article-title":"Pulsed near infrared transcranial and intranasal photobiomodulation significantly modulates neural oscillations: a pilot exploratory study","volume":"9","author":"Zomorrodi","year":"2019","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1117\/1.NPh.3.3.031404","article-title":"Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis","volume":"34","author":"Cassano","year":"2016","journal-title":"Photomed Laser Surg"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1007\/s10803-019-04348-8","article-title":"Effects of transcranial photobiomodulation on adults with autism spectrum disorder: a pilot study","volume":"50","author":"Ceranoglu","year":"2020","journal-title":"J Autism Dev Disord"},{"key":"B30","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/children9050755","article-title":"Transcranial photobiomodulation in autism spectrum disorders: a review","volume":"80","author":"Pallanti","year":"2016","journal-title":"J Psychiatr Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1221193","DOI":"10.3389\/fneur.2024.1221193","article-title":"A randomized sham-controlled clinical trial evaluating the safety and efficacy of transcranial photobiomodulation to improve symptoms of autism spectrum disorder and brain electrophysiology in children aged 2\u20136 years","volume":"15","author":"Fradkin","year":"2024","journal-title":"Front Neurol"},{"key":"B32","volume-title":"Diagnostic and Statistical Manual of Mental Disorders: DSM-5","year":"2013"},{"key":"B33","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1177\/0734282911400873","article-title":"Test review: E. Schopler, M. E. Van bourgondien, G. J. Wellman, & S. R. Love childhood autism rating scale. Los Angeles, CA: western psychological services, 2010","volume":"29","author":"Vaughan","year":"2011","journal-title":"J Psychoeduc Assess"},{"key":"B34","doi-asserted-by":"publisher","first-page":"230005","DOI":"10.3389\/fpsyt.2017.00121","article-title":"How useful is electroencephalography in the diagnosis of autism spectrum disorders and the delineation of subtypes: a systematic review","volume":"8","author":"Gurau","year":"2017","journal-title":"Front Psychiatry"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40810-014-0001-5","article-title":"EEG changes associated with autistic spectrum disorders","volume":"1","author":"Boutros","year":"2015","journal-title":"Neuropsychiatr Electrophysiol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"3073","DOI":"10.1007\/s00221-022-06483-8","article-title":"Motor networks in children with autism spectrum disorder: a systematic review on EEG studies","volume":"240","author":"Bo","year":"2022","journal-title":"Exp Brain Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"2228","DOI":"10.3390\/s23042228","article-title":"Energy-efficient EEG-based scheme for autism spectrum disorder detection using wearable sensors","volume":"23","author":"Alhassan","year":"2023","journal-title":"Sensors"},{"key":"B38","doi-asserted-by":"publisher","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":"B39","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s00787-021-01864-w","article-title":"Correction to: response (minimum clinically relevant change) in ASD symptoms after an intervention according to CARS-2: consensus from an expert elicitation procedure","volume":"32","author":"Jurek","year":"2023","journal-title":"Eur Child Adolesc Psychiatry"},{"key":"B40","volume-title":"Aberrant Behavior Checklist Manual","author":"Aman","year":"1986"},{"key":"B41","volume-title":"Social Responsiveness Scale, Second Edition (SRS-2)","author":"Constantino","year":"2012"},{"key":"B42","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.neuron.2018.09.023","article-title":"Working memory 2.0","volume":"100","author":"Miller","year":"2018","journal-title":"Neuron"},{"key":"B43","doi-asserted-by":"publisher","first-page":"21834","DOI":"10.1073\/pnas.1914180116","article-title":"Directional coupling of slow and fast hippocampal gamma with neocortical alpha\/beta oscillations in human episodic memory","volume":"116","author":"Griffiths","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B44","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.bbr.2015.09.011","article-title":"Electrophysiological CNS-processes related to associative learning in humans,","volume":"296","author":"Christoffersen","year":"2016","journal-title":"Behav Brain Res"},{"key":"B45","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1093\/brain\/awab095","article-title":"Consciousness among delta waves: a paradox?","volume":"144","author":"Frohlich","year":"2021","journal-title":"Brain"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1152\/jn.00249.2015","article-title":"Delta rhythm in wakefulness: evidence from intracranial recordings in human beings","volume":"114","author":"Sachdev","year":"2015","journal-title":"J Neurophysiol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41514-022-00093-y","article-title":"Integrated cognitive and physical fitness training enhances attention abilities in older adults","volume":"8","author":"Anguera","year":"2022","journal-title":"NPJ Aging"},{"key":"B48","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1073\/pnas.0534746100","article-title":"Therapeutic photobiomodulation for methanol-induced retinal toxicity","volume":"100","author":"Eells","year":"2003","journal-title":"Proc Natl Acad Sci USA"},{"key":"B49","doi-asserted-by":"publisher","first-page":"105928","DOI":"10.1016\/j.nbd.2022.105928","article-title":"Delta oscillation coupled propagating fast ripples precede epileptiform discharges in patients with focal epilepsy","volume":"175","author":"Weiss","year":"2022","journal-title":"Neurobiol Dis"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1866-1955-5-24","article-title":"Resting state EEG abnormalities in autism spectrum disorders","volume":"5","author":"Wang","year":"2013","journal-title":"J Neurodev Disord"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e39127","DOI":"10.1371\/journal.pone.0039127","article-title":"Developmental trajectories of resting EEG power: an endophenotype of autism spectrum disorder","volume":"7","author":"Tierney","year":"2012","journal-title":"PLoS One"},{"key":"B52","doi-asserted-by":"publisher","first-page":"105928","DOI":"10.1016\/j.nbd.2022.105928","article-title":"Delta oscillation coupled propagating fast ripples precede epileptiform discharges in patients with focal epilepsy","volume":"175","author":"Weiss","year":"2022","journal-title":"Neurobiol Dis"}],"container-title":["Frontiers in Child and Adolescent Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frcha.2025.1477839\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T06:59:58Z","timestamp":1738133998000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frcha.2025.1477839\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,29]]},"references-count":52,"alternative-id":["10.3389\/frcha.2025.1477839"],"URL":"https:\/\/doi.org\/10.3389\/frcha.2025.1477839","relation":{},"ISSN":["2813-4540"],"issn-type":[{"value":"2813-4540","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,29]]},"article-number":"1477839"}}