{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T07:04:31Z","timestamp":1784012671355,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,10]]},"group-title":"Neurology","reference-count":82,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Intellectual and Developmental Disabilities Research Center","award":["P50HD105351"],"award-info":[{"award-number":["P50HD105351"]}]},{"name":"International Research Center for Neurointelligence"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Rett syndrome (RTT), a rare neurodevelopmental disorder caused primarily by pathogenic variants in the\n                    <jats:italic>MECP2<\/jats:italic>\n                    gene, is characterized by severe cognitive, motor, and autonomic impairments. Atypical sensory processing\u2014including co-occurring hypo- and hyper-responsivity\u2014is a core yet poorly understood feature. While evoked potentials (EPs) show delayed and attenuated sensory responses in RTT, the underlying mechanisms of these impairments remain unclear. Inter-trial phase coherence (ITPC), which quantifies trial-by-trial neural response consistency, offers a promising functional biomarker of variability in sensory processing.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We characterized caregiver-reported sensory responsivity in 32 individuals with RTT (all female) and 28 typically developing controls (26 female, 2 male). EPs were then recorded during passive visual and auditory stimulation and ITPC was computed to assess whether variability in the timing of neural responses could account for reduced EP amplitudes and atypical sensory responsivity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Hypo- and hyper-responsivity to sensory stimuli were both significantly elevated in RTT and were positively correlated, co-occurring within individuals. ITPC was significantly reduced in RTT across visual and auditory modalities and was associated with reduced EP amplitudes. Notably, reduced ITPC in visual-evoked potentials was further associated with elevated visual responsivity and greater behavioral symptom severity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Increased variability in neural response timing may contribute to both reduced EPs and atypical sensory responsivity in RTT, supporting ITPC as a functional biomarker. Decreased temporal precision of neural activity may explain the co-occurrence of hypo- and hyper-responsivity and provide a unifying framework for sensory dysfunction across neurodevelopmental disorders.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.07.26357400","type":"posted-content","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T23:20:10Z","timestamp":1783725610000},"source":"Crossref","is-referenced-by-count":0,"title":["Variability in sensory processing and evoked potentials in Rett syndrome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8821-8885","authenticated-orcid":false,"given":"Devorah","family":"Kranz","sequence":"first","affiliation":[{"name":"Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Szilagyi","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen N","family":"Sabol","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Nelson","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4192-4720","authenticated-orcid":false,"given":"April R","family":"Levin","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2807-803X","authenticated-orcid":false,"given":"Michela","family":"Fagiolini","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071323152935000_2026.07.07.26357400v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"2026071323152935000_2026.07.07.26357400v1.2","doi-asserted-by":"crossref","first-page":"253","DOI":"10.31887\/DCNS.2012.14.3\/jneul","article-title":"The relationship of Rett syndrome and MECP2 disorders to autism","volume":"14","year":"2012","journal-title":"Dialogues Clin Neurosci"},{"key":"2026071323152935000_2026.07.07.26357400v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.10.001"},{"key":"2026071323152935000_2026.07.07.26357400v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30217-9"},{"key":"2026071323152935000_2026.07.07.26357400v1.5","doi-asserted-by":"publisher","DOI":"10.5014\/ajot.61.2.190"},{"key":"2026071323152935000_2026.07.07.26357400v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-019-04180-0"},{"key":"2026071323152935000_2026.07.07.26357400v1.7","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/01.HRP.0000445143.08773.58","article-title":"Sensory Symptoms in Autism Spectrum Disorders","volume":"22","year":"2014","journal-title":"Harv Rev Psychiatry"},{"key":"2026071323152935000_2026.07.07.26357400v1.8","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41398-019-0463-0","article-title":"Auditory sensory memory span for duration is severely curtailed in females with Rett syndrome","volume":"9","year":"2019","journal-title":"Transl Psychiatry"},{"key":"2026071323152935000_2026.07.07.26357400v1.9","doi-asserted-by":"publisher","DOI":"10.3390\/genes13040671"},{"key":"2026071323152935000_2026.07.07.26357400v1.10","doi-asserted-by":"publisher","DOI":"10.1177\/1362361320959959"},{"key":"2026071323152935000_2026.07.07.26357400v1.11","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1080\/09638288.2017.1414887","article-title":"Quality of life and its related factors for adults with autism spectrum disorder","volume":"41","year":"2019","journal-title":"Disabil Rehabil"},{"key":"2026071323152935000_2026.07.07.26357400v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcn.2017.04.010"},{"key":"2026071323152935000_2026.07.07.26357400v1.13","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-022-00534-1"},{"key":"2026071323152935000_2026.07.07.26357400v1.14","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e3182130c54"},{"key":"2026071323152935000_2026.07.07.26357400v1.15","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-021-00435-9"},{"key":"2026071323152935000_2026.07.07.26357400v1.16","doi-asserted-by":"publisher","DOI":"10.1007\/s10803-021-05186-3"},{"key":"2026071323152935000_2026.07.07.26357400v1.17","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1007\/s10803-017-3422-8","article-title":"The Glasgow Sensory Questionnaire: Validation of a French Language Version and Refinement of Sensory Profiles of People with High Autism-Spectrum Quotient","volume":"48","year":"2018","journal-title":"J Autism Dev Disord"},{"key":"2026071323152935000_2026.07.07.26357400v1.18","doi-asserted-by":"publisher","DOI":"10.1101\/2025.09.21.25336283"},{"key":"2026071323152935000_2026.07.07.26357400v1.19","doi-asserted-by":"crossref","unstructured":"Suter B , Pehlivan D , Ak M , Harris HK , Lyons-Warren AM (2024): Sensory experiences questionnaire unravels differences in sensory profiles between MECP2-related disorders. Autism Res aur.3112.","DOI":"10.1002\/aur.3112"},{"key":"2026071323152935000_2026.07.07.26357400v1.20","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24513"},{"key":"2026071323152935000_2026.07.07.26357400v1.21","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/ana.26029","article-title":"Multisite Study of Evoked Potentials in Rett Syndrome","volume":"89","year":"2021","journal-title":"Ann Neurol"},{"key":"2026071323152935000_2026.07.07.26357400v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2006.02.011"},{"key":"2026071323152935000_2026.07.07.26357400v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2019.11.003"},{"key":"2026071323152935000_2026.07.07.26357400v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39242-x"},{"key":"2026071323152935000_2026.07.07.26357400v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.03.027"},{"key":"2026071323152935000_2026.07.07.26357400v1.26","doi-asserted-by":"crossref","unstructured":"Courchesne E (1990): Chronology of postnatal human brain development: Event-related potential, positron emission tomography, myelinogenesis, and synaptogenesis studies. Event-Relat Brain Potentials Basic Issues Appl 210\u2013241.","DOI":"10.1093\/oso\/9780195048919.003.0014"},{"key":"2026071323152935000_2026.07.07.26357400v1.27","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.841236"},{"key":"2026071323152935000_2026.07.07.26357400v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-8760(98)00015-4"},{"key":"2026071323152935000_2026.07.07.26357400v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)00377-4"},{"key":"2026071323152935000_2026.07.07.26357400v1.30","doi-asserted-by":"crossref","first-page":"e787","DOI":"10.1038\/tp.2016.48","article-title":"Reduced habituation of auditory evoked potentials indicate cortical hyper-excitability in Fragile X Syndrome","volume":"6","year":"2016","journal-title":"Transl Psychiatry"},{"key":"2026071323152935000_2026.07.07.26357400v1.31","doi-asserted-by":"crossref","first-page":"987184","DOI":"10.3389\/fnint.2022.987184","article-title":"Neural response to repeated auditory stimuli and its association with early language ability in male children with Fragile X syndrome","volume":"16","year":"2022","journal-title":"Front Integr Neurosci"},{"key":"2026071323152935000_2026.07.07.26357400v1.32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.bandc.2018.11.001","article-title":"Feasibility of using auditory event-related potentials to investigate learning and memory in nonverbal individuals with Angelman syndrome","volume":"128","year":"2018","journal-title":"Brain Cogn"},{"key":"2026071323152935000_2026.07.07.26357400v1.33","doi-asserted-by":"publisher","DOI":"10.13140\/RG.2.2.35857.38241"},{"key":"2026071323152935000_2026.07.07.26357400v1.34","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16285"},{"key":"2026071323152935000_2026.07.07.26357400v1.35","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/S0387-7604(89)80077-4","article-title":"Neurophysiological findings in the Rett syndrome, I: EMG, conduction velocity, EEG and somatosensory-evoked potential studies","volume":"11","year":"1989","journal-title":"Brain Dev"},{"key":"2026071323152935000_2026.07.07.26357400v1.36","first-page":"226","article-title":"Auditory evoked potentials in Rett syndrome","volume":"5","year":"1994","journal-title":"J Am Acad Audiol"},{"key":"2026071323152935000_2026.07.07.26357400v1.37","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-016-9166-5"},{"key":"2026071323152935000_2026.07.07.26357400v1.38","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s11689-024-09544-x","article-title":"Probing a neural unreliability account of auditory sensory processing atypicalities in Rett Syndrome","volume":"16","year":"2024","journal-title":"J Neurodev Disord"},{"key":"2026071323152935000_2026.07.07.26357400v1.39","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/s41398-020-00877-4","article-title":"Atypical processing of tones and phonemes in Rett Syndrome as biomarkers of disease progression","volume":"10","year":"2020","journal-title":"Transl Psychiatry"},{"key":"2026071323152935000_2026.07.07.26357400v1.40","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.brainres.2017.08.028","article-title":"Distinguishing response to names in Rett and MECP2 Duplication syndrome: An ERP study of auditory social information processing","volume":"1675","year":"2017","journal-title":"Brain Res"},{"key":"2026071323152935000_2026.07.07.26357400v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.12.004"},{"key":"2026071323152935000_2026.07.07.26357400v1.42","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1506499112"},{"key":"2026071323152935000_2026.07.07.26357400v1.43","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/acn3.70197","article-title":"Visual Recovery Reflects Cortical Sensitivity in Rett Syndrome","volume":"13","year":"2026","journal-title":"Ann Clin Transl Neurol"},{"key":"2026071323152935000_2026.07.07.26357400v1.44","first-page":"543","volume-title":"Handbook of Clinical Neurology","volume":"160","year":"2019"},{"key":"2026071323152935000_2026.07.07.26357400v1.45","unstructured":"Luck SJ (2005): An Introduction to the Event-Related Potential Technique. Cambridge, Mass.: MIT Press."},{"key":"2026071323152935000_2026.07.07.26357400v1.46","doi-asserted-by":"publisher","DOI":"10.1126\/science.1066168"},{"key":"2026071323152935000_2026.07.07.26357400v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2004.03.008"},{"key":"2026071323152935000_2026.07.07.26357400v1.48","doi-asserted-by":"publisher","DOI":"10.1007\/s10827-012-0424-6"},{"key":"2026071323152935000_2026.07.07.26357400v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2006.06.003"},{"key":"2026071323152935000_2026.07.07.26357400v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.09.004"},{"key":"2026071323152935000_2026.07.07.26357400v1.51","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2011.00051"},{"key":"2026071323152935000_2026.07.07.26357400v1.52","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41398-019-0672-6","article-title":"Reduced visual evoked potential amplitude in autism spectrum disorder, a variability effect?","volume":"9","year":"2019","journal-title":"Transl Psychiatry"},{"key":"2026071323152935000_2026.07.07.26357400v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2018.04.599"},{"key":"2026071323152935000_2026.07.07.26357400v1.54","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-015-0065-5"},{"key":"2026071323152935000_2026.07.07.26357400v1.55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.rasd.2017.01.011","article-title":"Inter-trial coherence of medial frontal theta oscillations linked to differential feedback processing in youth and young adults with autism","volume":"37","year":"2017","journal-title":"Res Autism Spectr Disord"},{"key":"2026071323152935000_2026.07.07.26357400v1.56","unstructured":"Dunn, W. Sensory Profile 2. NCS Pearson, Inc., 2014. (n.d.):"},{"key":"2026071323152935000_2026.07.07.26357400v1.57","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000291011.54508.aa"},{"key":"2026071323152935000_2026.07.07.26357400v1.58","doi-asserted-by":"crossref","unstructured":"Guy W. Clinical global impressions. In: Guy W , editor. ECDEU assessment manual for psychopharmacology (Revised) National Institute of Mental Health; Rockville, Maryland: 1976. pp. 217\u2013221. (n.d.):","DOI":"10.1037\/e591322011-001"},{"key":"2026071323152935000_2026.07.07.26357400v1.59","doi-asserted-by":"publisher","DOI":"10.1177\/0883073815579707"},{"key":"2026071323152935000_2026.07.07.26357400v1.60","doi-asserted-by":"publisher","DOI":"10.1111\/1469-7610.00236"},{"key":"2026071323152935000_2026.07.07.26357400v1.61","doi-asserted-by":"crossref","first-page":"1229553","DOI":"10.3389\/fped.2023.1229553","article-title":"A review of the Rett Syndrome Behaviour Questionnaire and its utilization in the assessment of symptoms associated with Rett syndrome","volume":"11","year":"2023","journal-title":"Front Pediatr"},{"key":"2026071323152935000_2026.07.07.26357400v1.62","doi-asserted-by":"publisher","DOI":"10.1352\/1944-7558-128.3.237"},{"key":"2026071323152935000_2026.07.07.26357400v1.63","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007316"},{"key":"2026071323152935000_2026.07.07.26357400v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2022.106704"},{"key":"2026071323152935000_2026.07.07.26357400v1.65","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1311141111"},{"key":"2026071323152935000_2026.07.07.26357400v1.66","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/acn3.533","article-title":"Placebo-controlled crossover assessment of mecasermin for the treatment of Rett syndrome","volume":"5","year":"2018","journal-title":"Ann Clin Transl Neurol"},{"key":"2026071323152935000_2026.07.07.26357400v1.67","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/ajmg.b.30270","article-title":"The association between behavior and genotype in Rett syndrome using the Australian Rett Syndrome Database","volume":"141B","year":"2006","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"2026071323152935000_2026.07.07.26357400v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.117130"},{"key":"2026071323152935000_2026.07.07.26357400v1.69","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00513"},{"key":"2026071323152935000_2026.07.07.26357400v1.70","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00097"},{"key":"2026071323152935000_2026.07.07.26357400v1.71","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2003.10.009"},{"key":"2026071323152935000_2026.07.07.26357400v1.72","doi-asserted-by":"publisher","DOI":"10.1007\/s10633-007-9111-8"},{"key":"2026071323152935000_2026.07.07.26357400v1.73","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-2457(99)00236-9"},{"key":"2026071323152935000_2026.07.07.26357400v1.74","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhq170"},{"key":"2026071323152935000_2026.07.07.26357400v1.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.05.033"},{"key":"2026071323152935000_2026.07.07.26357400v1.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.08.016"},{"key":"2026071323152935000_2026.07.07.26357400v1.77","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55639"},{"key":"2026071323152935000_2026.07.07.26357400v1.78","doi-asserted-by":"publisher","DOI":"10.1038\/nature09582"},{"key":"2026071323152935000_2026.07.07.26357400v1.79","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1817222116"},{"key":"2026071323152935000_2026.07.07.26357400v1.80","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhz085"},{"key":"2026071323152935000_2026.07.07.26357400v1.81","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3710"},{"key":"2026071323152935000_2026.07.07.26357400v1.82","doi-asserted-by":"publisher","DOI":"10.1101\/2025.07.21.25331927"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.07.26357400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T06:15:41Z","timestamp":1784009741000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.07.07.26357400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":82,"URL":"https:\/\/doi.org\/10.64898\/2026.07.07.26357400","relation":{},"subject":[],"published":{"date-parts":[[2026,7,10]]},"subtype":"preprint"}}