{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T17:25:21Z","timestamp":1787246721651,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Fetal Alcohol Spectrum Disorder (FASD) is a preventable neurodevelopmental condition associated with dysfunction of fronto-subcortical networks affecting attention, executive function, and behavioral regulation. Central auditory processing difficulties frequently persist despite preserved peripheral hearing, complicating clinical evaluation when behavioral testing is limited or unreliable, and objective markers that do not depend on behavioral cooperation are therefore needed. This exploratory observational case study investigated whether Frequency-Following Responses (FFRs) can capture measurable within-subject change in speech-evoked neural encoding in a pediatric patient with FASD. Methods: FFRs were recorded at two time points bracketing an eight-session period of non-invasive superficial neuromodulation (NESA\u00ae) in an 8-year-old girl with FASD, using speech syllables (\/da\/, \/ba\/, \/ga\/) presented monaurally at 80 dB SPL. Two-tailed block-level Mann\u2013Whitney U tests with rank-biserial correlations compared peak latencies, sustained pitch-tracking metrics (pitch strength, pitch error), onset stimulus\u2013response correlation, and signal-to-noise ratio. Results: Sustained pitch-tracking metrics differed between time points, with increased pitch strength and reduced pitch error, whereas onset peak latencies, onset cross-correlation, and signal-to-noise ratio remained stable. Peak C, marking the transition to the sustained portion of the response, occurred earlier at the post-assessment in all six stimulus\u2013ear combinations. The differences were therefore selective to sustained encoding rather than to onset timing or recording quality. Conclusions: FFR-derived pitch-encoding metrics detected measurable within-subject change, providing proof of concept for the feasibility of FFRs as a candidate objective tool for longitudinal monitoring of speech-evoked neural encoding in pediatric FASD. This single-case observation does not evaluate diagnostic accuracy, sensitivity, specificity, or discrimination from typically developing children, and therefore does not establish FFR as a validated diagnostic technique. The findings are hypothesis-generating and motivate controlled longitudinal studies.<\/jats:p>","DOI":"10.3390\/children13081116","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:05:19Z","timestamp":1787241919000},"page":"1116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Frequency-Following Responses for Objective Neurophysiological Monitoring in Pediatric Fetal Alcohol Spectrum Disorder: A Proof of Concept Case Study During Non-Invasive Neuromodulation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8796-5435","authenticated-orcid":false,"given":"Sheila","family":"Templado","sequence":"first","affiliation":[{"name":"International Doctoral School, Catholic University San Antonio of Murcia (UCAM), 30107 Murcia, Spain"},{"name":"Cl\u00ednica Templado\u2014Advanced Audiology and Otolaryngology, 30005 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1015-847X","authenticated-orcid":false,"given":"Raquel","family":"Medina-Ramirez","sequence":"additional","affiliation":[{"name":"Soc-Dig Research Group, University of Las Palmas de Gran Canaria, 35001 Las Palmas de Gran Canaria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Savio","sequence":"additional","affiliation":[{"name":"Intelligent Hearing Systems, R&D Department, Miami, FL 33143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"Almela","sequence":"additional","affiliation":[{"name":"Cl\u00ednica Templado\u2014Advanced Audiology and Otolaryngology, 30005 Murcia, Spain"},{"name":"Department of Otolaryngology, Virgen de la Arrixaca University Hospital, 30120 El Palmar, Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco J.","family":"Garc\u00eda-Purri\u00f1os","sequence":"additional","affiliation":[{"name":"International Doctoral School, Catholic University San Antonio of Murcia (UCAM), 30107 Murcia, Spain"},{"name":"Department of Otolaryngology, Los Arcos del Mar Menor University Hospital, 30739 San Javier, Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1007\/s11065-011-9163-0","article-title":"Imaging the Impact of Prenatal Alcohol Exposure on the Structure of the Developing Human Brain","volume":"21","author":"Lebel","year":"2011","journal-title":"Neuropsychol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1111\/acer.14040","article-title":"Fetal Alcohol Spectrum Disorders: A Review of the Neurobehavioral Deficits Associated With Prenatal Alcohol Exposure","volume":"43","author":"Mattson","year":"2019","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11065-011-9166-x","article-title":"Fetal Alcohol Spectrum Disorders: An Overview","volume":"21","author":"Riley","year":"2011","journal-title":"Neuropsychol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1111\/j.1530-0277.2012.01769.x","article-title":"Delays in Auditory Processing Identified in Preschool Children with FASD","volume":"36","author":"Stephen","year":"2012","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e382","DOI":"10.1542\/peds.2009-2826","article-title":"Nature of Auditory Processing Disorder in Children","volume":"126","author":"Moore","year":"2010","journal-title":"Pediatrics"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kraus, N., Anderson, S., White-Schwoch, T., Fay, R.R., and Popper, A.N. (2017). The Frequency-Following Response: A Window into Human Communication. The Frequency-Following Response: A Window into Human Communication, Springer International Publishing.","DOI":"10.1007\/978-3-319-47944-6_1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/j.1469-8986.2009.00928.x","article-title":"The Scalp-Recorded Brainstem Response to Speech: Neural Origins and Plasticity","volume":"47","author":"Chandrasekaran","year":"2010","journal-title":"Psychophysiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1097\/AUD.0b013e3181cdb272","article-title":"Auditory Brain Stem Response to Complex Sounds: A Tutorial","volume":"31","author":"Skoe","year":"2010","journal-title":"Ear Hear."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s00221-017-5164-4","article-title":"Children with Autism Spectrum Disorder Have Unstable Neural Responses to Sound","volume":"236","author":"Krizman","year":"2018","journal-title":"Exp. Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"107807","DOI":"10.1016\/j.biopsycho.2019.107807","article-title":"Increased Subcortical Neural Responses to Repeating Auditory Stimulation in Children with Autism Spectrum Disorder","volume":"149","author":"Cornella","year":"2020","journal-title":"Biol. Psychol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Donadon, C., Sanfins, M.D., Sanches, A.B., Cardoso, G.L.d.S., de Mello, A.G.P., Skarzynski, P.H., and Colella-Santos, M.F. (2026). Effect of Lateralization, Age, and Sex on Frequency Following Response in Children: Neural Speech Encoding to a 170 ms [da] Stimulus. Life, 16.","DOI":"10.3390\/life16040695"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Templado, S., Savio, G., and Garc\u00eda-Purri\u00f1os, F. (2026). Neural Speech Encoding in Fetal Alcohol Spectrum Disorder: An Exploratory Study Using Frequency-Following Responses. Front. Neurosci., 20.","DOI":"10.3389\/fnins.2026.1871045"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11070","DOI":"10.1038\/ncomms11070","article-title":"Cortical Contributions to the Auditory Frequency-Following Response Revealed by MEG","volume":"7","author":"Coffey","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101324","DOI":"10.1016\/j.cobeha.2023.101324","article-title":"Contributions of the Subcortical Auditory System to Predictive Coding and the Neural Encoding of Speech","volume":"54","author":"Escera","year":"2023","journal-title":"Curr. Opin. Behav. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"117866","DOI":"10.1016\/j.neuroimage.2021.117866","article-title":"Neural Generators of the Frequency-Following Response Elicited to Stimuli of Low and High Frequency: A MEG Study","volume":"231","author":"Kurkela","year":"2021","journal-title":"NeuroImage"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1016\/S1053-8119(03)00389-6","article-title":"Prefrontal Cortex Involvement in Preattentive Auditory Deviance Detection","volume":"20","author":"Doeller","year":"2003","journal-title":"NeuroImage"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"B\u00e1ez-Su\u00e1rez, A., Padr\u00f3n-Rodr\u00edguez, I., Castellano-Moreno, E., Gonz\u00e1lez-Gonz\u00e1lez, E., Quintana-Montesdeoca, M.P., and Medina-Ramirez, R.I. (2023). Application of Non-Invasive Neuromodulation in Children with Neurodevelopmental Disorders to Improve Their Sleep Quality and Constipation. BMC Pediatr., 23.","DOI":"10.1186\/s12887-023-04307-4"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.clinph.2016.10.087","article-title":"Evidence-Based Guidelines on the Therapeutic Use of Transcranial Direct Current Stimulation (tDCS)","volume":"128","author":"Lefaucheur","year":"2017","journal-title":"Clin. Neurophysiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"s232","DOI":"10.1016\/j.eurpsy.2016.01.578","article-title":"Superficial Neurostimulation Application, Alpha Rhythm and Clinical Effects","volume":"33","author":"Rico","year":"2016","journal-title":"Eur. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Molina-Cedr\u00e9s, F., Medina-Ram\u00edrez, R., B\u00e1ez-Su\u00e1rez, A., V\u00edlchez-Barrera, M., Garc\u00eda-Quintana, M., Hernandez-P\u00e9rez, A., Garc\u00eda-Rodr\u00edguez, I., \u00c1lamo-Arce, D., and Etopa-Bitata, M.d.P. (2025). Impact of NESA Non-Invasive Neuromodulation on Sleep, Behavior, and Sensory Profile in Children with Autism Spectrum Disorder. Children, 12.","DOI":"10.3390\/children12121599"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.2147\/NDT.S565304","article-title":"Efficacy and Safety of Neuromodulation Interventions for Autism Spectrum Disorders with Comorbidities: A Systematic Review","volume":"21","author":"Wu","year":"2025","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Teruel-Hern\u00e1ndez, E., L\u00f3pez-Pina, J.A., Souto-Camba, S., B\u00e1ez-Su\u00e1rez, A., Medina-Ram\u00edrez, R., and G\u00f3mez-Conesa, A. (2023). Improving Sleep Quality, Daytime Sleepiness, and Cognitive Function in Patients with Dementia by Therapeutic Exercise and NESA Neuromodulation: A Multicenter Clinical Trial. Int. J. Environ. Res. Public Health, 20.","DOI":"10.3390\/ijerph20217027"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107779","DOI":"10.1016\/j.heares.2019.107779","article-title":"Analyzing the FFR: A Tutorial for Decoding the Richness of Auditory Function","volume":"382","author":"Krizman","year":"2019","journal-title":"Hear. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.beth.2010.08.006","article-title":"Combining Nonoverlap and Trend for Single-Case Research: Tau-U","volume":"42","author":"Parker","year":"2011","journal-title":"Behav. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1518687","DOI":"10.1080\/23311908.2018.1518687","article-title":"Interpreting Kendall\u2019s Tau and Tau-U for Single-Case Experimental Designs","volume":"5","author":"Brossart","year":"2018","journal-title":"Cogent Psychol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1097\/01.aud.0000179687.71662.6e","article-title":"Brain Stem Response to Speech: A Biological Marker of Auditory Processing","volume":"26","author":"Johnson","year":"2005","journal-title":"Ear Hear."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neuroimage.2018.03.060","article-title":"Subcortical Sources Dominate the Neuroelectric Auditory Frequency-Following Response to Speech","volume":"175","author":"Bidelman","year":"2018","journal-title":"NeuroImage"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1152\/jn.00112.2019","article-title":"Case Studies in Neuroscience: Subcortical Origins of the Frequency-Following Response","volume":"122","author":"Anderson","year":"2019","journal-title":"J. Neurophysiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1152\/jn.00104.2020","article-title":"Case Studies in Neuroscience: Cortical Contributions to the Frequency-Following Response Depend on Subcortical Synchrony","volume":"125","author":"Krizman","year":"2021","journal-title":"J. Neurophysiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.clinph.2010.07.025","article-title":"Peripheral Electrical Stimulation to Induce Cortical Plasticity: A Systematic Review of Stimulus Parameters","volume":"122","author":"Chipchase","year":"2011","journal-title":"Clin. Neurophysiol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Schabrun, S.M., Ridding, M.C., Galea, M.P., Hodges, P.W., and Chipchase, L.S. (2012). Primary Sensory and Motor Cortex Excitability Are Co-Modulated in Response to Peripheral Electrical Nerve Stimulation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051298"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.tins.2005.02.003","article-title":"Brainstem Origins for Cortical \u2019What\u2019 and \u2019Where\u2019 Pathways in the Auditory System","volume":"28","author":"Kraus","year":"2005","journal-title":"Trends Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1016\/j.clinph.2007.04.026","article-title":"The Mismatch Negativity (MMN) in Basic Research of Central Auditory Processing: A Review","volume":"118","author":"Paavilainen","year":"2007","journal-title":"Clin. Neurophysiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Plakke, B., and Romanski, L.M. (2014). Auditory Connections and Functions of Prefrontal Cortex. Front. Neurosci., 8.","DOI":"10.3389\/fnins.2014.00199"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Schochat, E., Rocha-Muniz, C.N., and Filippini, R. (2017). Understanding Auditory Processing Disorder Through the FFR. The Frequency-Following Response: A Window into Human Communication, Springer International Publishing.","DOI":"10.1007\/978-3-319-47944-6_9"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1044\/2018_JSLHR-H-18-0359","article-title":"Listening Difficulties in Children With Fetal Alcohol Spectrum Disorders: More Than a Problem of Audibility","volume":"62","author":"McLaughlin","year":"2019","journal-title":"J. Speech Lang. Hear. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.heares.2018.11.001","article-title":"The Frequency-Following Response (FFR) to Speech Stimuli: A Normative Dataset in Healthy Newborns","volume":"371","author":"Almeida","year":"2019","journal-title":"Hear. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.heares.2011.12.005","article-title":"Test-Retest Consistency of Speech-Evoked Auditory Brainstem Responses in Typically-Developing Children","volume":"284","author":"Hornickel","year":"2012","journal-title":"Hear. Res."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/8\/1116\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:33:25Z","timestamp":1787243605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/8\/1116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":38,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["children13081116"],"URL":"https:\/\/doi.org\/10.3390\/children13081116","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}