{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:29:40Z","timestamp":1790116180080,"version":"4.0.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001735","name":"Milton and Tamar Maltz Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>People with hypermobile Ehlers\u2013Danlos syndrome (hEDS) experience multisystemic dysfunction with varying severity and unpredictability of flare occurrence. Cohort studies suggest that individuals with hEDS have a higher risk for autonomic dysfunction. The gold standard for assessing autonomic function, clinically, is the heart rate variability (HRV) assessment from 24-h Holter monitor electrocardiogram data, but this is expensive and can only be performed in short durations. Since their advent, biometric devices have been a non-invasive method for tracking HRV to assess autonomic function. This study aimed to understand the intra- and inter-individual variability in autonomic function and to associate this variability with gastrointestinal symptoms in individuals with hEDS using wearable devices.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 122 days of biometric device data from 26 individuals, including 35 days highlighted as high gastrointestinal (GI) dysfunction and 48 days as low GI dysfunction. Utilizing wavelet analysis to assess the frequency domains of heart rate signals, we compared participants\u2019 HRV data for high, low, very low (VLF), and ultralow (ULF) frequency domains associated with physiological differences.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found a significant difference between the VLF and ULF signals on high-GI symptom days compared with low-symptoms days for 92 and 76% of the signals sampled, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our pilot data show a change in HRV for individuals with hEDS experiencing a flare day for a single-body system. Future research will focus on evaluating the relationship between longitudinal multisystemic symptom severity fluctuations and HRV.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1499582","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T20:10:32Z","timestamp":1736971832000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Tracking changes in autonomic function by coupled analysis of wavelet-based dispersion of heart rate variability and gastrointestinal symptom severity in individuals with hypermobile Ehlers\u2013Danlos syndrome"],"prefix":"10.3389","volume":"15","author":[{"given":"Sarah A.","family":"Mathena","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Laukaitis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer G.","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/ajmg.c.31552","article-title":"The 2017 international classification of the Ehlers\u2013Danlos syndromes","volume":"175","author":"Malfait","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1002\/ajmg.a.61459","article-title":"Utilization of the 2017 diagnostic criteria for hEDS by the Toronto GoodHope Ehlers\u2013Danlos syndrome clinic: a retrospective review","volume":"182","author":"McGillis","year":"2020","journal-title":"Am J Med Genet A"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1007\/s00296-021-04968-3","article-title":"Are patients with hypermobile Ehlers-Danlos syndrome or hypermobility spectrum disorder so different?","volume":"41","author":"Aubry-Rozier","year":"2021","journal-title":"Rheumatol Int"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e031365","DOI":"10.1136\/bmjopen-2019-031365","article-title":"Diagnosed prevalence of Ehlers-Danlos syndrome and hypermobility spectrum disorder in Wales, UK: a national electronic cohort study and case-control comparison","volume":"9","author":"Demmler","year":"2019","journal-title":"BMJ Open"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/j.mcna.2019.08.002","article-title":"Symptomatic joint hypermobility","volume":"103","author":"Tinkle","year":"2019","journal-title":"Med Clin North Am"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41572-020-0194-9","article-title":"The Ehlers\u2013Danlos syndromes","volume":"6","author":"Malfait","year":"2020","journal-title":"Nat Rev Dis Prim"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2012","DOI":"10.1002\/ajmg.a.62197","article-title":"Subtle differences in autonomic symptoms in people diagnosed with hypermobile Ehlers\u2013Danlos syndrome and hypermobility spectrum disorders","volume":"185","author":"Martinez","year":"2021","journal-title":"Am J Med Genet A"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1002\/ajmg.c.31546","article-title":"Gastrointestinal involvement in the Ehlers\u2013Danlos syndromes","volume":"175","author":"Fikree","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13013","article-title":"Gastrointestinal disorders in joint hypermobility syndrome\/Ehlers-Danlos syndrome hypermobility type: a review for the gastroenterologist","volume":"29","author":"Beckers","year":"2017","journal-title":"Neurogastroenterol Motil"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1002\/ajmg.c.31543","article-title":"Cardiovascular autonomic dysfunction in Ehlers\u2013Danlos syndrome\u2014hypermobile type","volume":"175","author":"Hakim","year":"2017","journal-title":"Am J Med Genet C"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.3390\/jcm10071392","article-title":"Assessment of gastrointestinal autonomic dysfunction: present and future perspectives","volume":"10","author":"Kornum","year":"2021","journal-title":"J Clin Med"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.semarthrit.2014.05.013","article-title":"Autonomic symptom burden in the hypermobility type of Ehlers\u2013Danlos syndrome: a comparative study with two other EDS types, fibromyalgia, and healthy controls","volume":"44","author":"De Wandele","year":"2014","journal-title":"Semin Arthritis Rheum"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2017\/9161865","article-title":"Orthostatic intolerance and postural orthostatic tachycardia syndrome in joint hypermobility syndrome\/Ehlers-Danlos syndrome, hypermobility type: Neurovegetative dysregulation or autonomic failure?","volume":"2017","author":"Celletti","year":"2017","journal-title":"Biomed Res Int"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.autneu.2018.02.006","article-title":"Postural tachycardia syndrome and other forms of orthostatic intolerance in Ehlers-Danlos syndrome","volume":"215","author":"Roma","year":"2018","journal-title":"Auton Neurosci Basic Clin"},{"key":"ref15","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-07371-2","volume-title":"Clinical autonomic dysfunction: Measurement, indications, therapies, and outcomes","author":"Colombo","year":"2015"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1093\/bmb\/ldy036","article-title":"Autonomic dysfunction and chronic disease","volume":"128","author":"Zalewski","year":"2018","journal-title":"Br Med Bull"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1111\/jgh.15927","article-title":"Hypermobile Ehlers-Danlos syndrome and disorders of the gastrointestinal tract: what the gastroenterologist needs to know","volume":"37","author":"Thwaites","year":"2022","journal-title":"J Gastroenterol Hepatol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1002\/ajmg.c.31938","article-title":"Overlap between irritable bowel syndrome and hypermobile Ehlers\u2013Danlos syndrome: an unexplored clinical phenotype?","volume":"187","author":"Choudhary","year":"2021","journal-title":"Am J Med Genet C: Semin Med Genet"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e7881","DOI":"10.7759\/cureus.7881","article-title":"Prevalence and predictors of gastrointestinal Dysmotility in patients with hypermobile Ehlers-Danlos syndrome: a tertiary care center experience","volume":"12","author":"Alomari","year":"2020","journal-title":"Cureus"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e13029","DOI":"10.1111\/nmo.13029","article-title":"Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome","volume":"29","author":"Fikree","year":"2017","journal-title":"Neurogastroenterol Motil"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e13975","DOI":"10.1111\/nmo.13975","article-title":"Functional gastrointestinal disorders are increased in joint hypermobility-related disorders with concomitant postural orthostatic tachycardia syndrome","volume":"32","author":"Tai","year":"2020","journal-title":"Neurogastroenterol Motil"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jpeds.2019.11.009","article-title":"Functional gastrointestinal disorders, autonomic nervous system dysfunction, and joint hypermobility in children: are they related?","volume":"218","author":"Velasco-Benitez","year":"2020","journal-title":"J Pediatr"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1111\/maq.12277","article-title":"\u201cJust one thing after another\u201d: recursive cascades and chronic conditions","volume":"30","author":"Manderson","year":"2016","journal-title":"Med Anthropol Q"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"100812","DOI":"10.1016\/j.gimo.2023.100812","article-title":"Comorbidity, misdiagnoses, and the diagnostic odyssey in patients with hypermobile Ehlers-Danlos syndrome","volume":"1","author":"Halverson","year":"2023","journal-title":"Genet Med Open"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1038\/ajg.2012.131","article-title":"Effect of gender on prevalence of irritable bowel syndrome in the community: systematic review and Meta-analysis","volume":"107","author":"Lovell","year":"2012","journal-title":"Off J Am Coll Gastroenterol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/ajg.2010.383","article-title":"Understanding gastrointestinal distress: a framework for clinical practice","volume":"106","author":"Spiegel","year":"2011","journal-title":"Am J Gastroenterol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1093\/jamiaopen\/ooz065","article-title":"Use of patient-generated health data across healthcare settings: implications for health systems","volume":"3","author":"Austin","year":"2020","journal-title":"JAMIA Open"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1002\/dvdy.220","article-title":"Hypermobile Ehlers-Danlos syndromes: complex phenotypes, challenging diagnoses, and poorly understood causes","volume":"250","author":"Gensemer","year":"2021","journal-title":"Dev Dyn"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1136\/heart.87.3.220","article-title":"Relation between QT and RR intervals is highly individual among healthy subjects: implications for heart rate correction of the QT interval","volume":"87","author":"Malik","year":"2002","journal-title":"Heart"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3389\/fpubh.2017.00258","article-title":"An overview of heart rate variability metrics and norms","volume":"5","author":"Shaffer","year":"2017","journal-title":"Front Public Health"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e34384","DOI":"10.2196\/34384","article-title":"The impact of wearable Technologies in Health Research: scoping review","volume":"10","author":"Huhn","year":"2022","journal-title":"JMIR Mhealth Uhealth"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"7146","DOI":"10.3390\/ijerph20247146","article-title":"Heart rate variability measurement through a smart wearable device: another breakthrough for personal health monitoring?","volume":"20","author":"Li","year":"2023","journal-title":"Int J Environ Res Public Health"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1007\/s00246-018-1881-0","article-title":"Heart rate variability and cardiopulmonary dysfunction in patients with Duchenne muscular dystrophy: a systematic review","volume":"39","author":"da Silva","year":"2018","journal-title":"Pediatr Cardiol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/978-3-319-07371-2_12","article-title":"The progression of autonomic dysfunction in chronic disease","volume-title":"Clinical autonomic dysfunction: Measurement, indications, therapies, and outcomes","author":"Colombo","year":"2015"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.3390\/s21041061","article-title":"Wearable devices suitable for monitoring twenty four hour heart rate variability in military populations","volume":"21","author":"Hinde","year":"2021","journal-title":"Sensors"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.autneu.2018.03.004","article-title":"Cognitive and psychological issues in postural tachycardia syndrome","volume":"215","author":"Raj","year":"2018","journal-title":"Auton Neurosci Basic Clin"},{"key":"ref37","volume-title":"Identifying the genetic basis of hypermobile Ehlers-Danlos syndrome (hEDS)","author":"Martinez","year":"2021"},{"key":"ref38","article-title":"Your personal digital fitness and health coach","year":"2016"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"301","DOI":"10.5535\/arm.2016.40.2.301","article-title":"Heart rate variability for quantification of autonomic dysfunction in fibromyalgia","volume":"40","author":"Kang","year":"2016","journal-title":"Ann Rehabil Med"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"399","DOI":"10.5772\/intechopen.87895","volume-title":"Wavelet theory","author":"Mohammady","year":"2021"},{"key":"ref41","first-page":"121","article-title":"Application of wavelet transform and its advantages compared to Fourier transform","volume":"13","author":"Sifuzzaman","year":"2009","journal-title":"J Phys Sci"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"785","DOI":"10.3390\/diagnostics13040785","article-title":"The role of heart rate variability (HRV) in different hypertensive syndromes","volume":"13","author":"Yugar","year":"2023","journal-title":"Diagnostics"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.21105\/joss.01237","article-title":"PyWavelets: a Python package for wavelet analysis","volume":"4","author":"Lee","year":"2019","journal-title":"JOSS"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1137\/1.9781611970104","volume-title":"Ten lectures on wavelets","author":"Daubechies","year":"1992"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3389\/fphys.2013.00026","article-title":"The LF\/HF ratio does not accurately measure cardiac sympatho-vagal balance","volume":"4","author":"Billman","year":"2013","journal-title":"Front Physiol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/978-1-4614-6227-9_11","article-title":"F-Test","volume-title":"Understanding statistics using R","author":"Schumacker","year":"2013"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1002\/ajmg.c.31538","article-title":"Hypermobile Ehlers\u2013Danlos syndrome (a.k.a. Ehlers\u2013Danlos syndrome type III and Ehlers\u2013Danlos syndrome hypermobility type): clinical description and natural history","volume":"175","author":"Tinkle","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"e160721189770","DOI":"10.2174\/1573403X16999201231203854","article-title":"Analysis of heart rate variability and implication of different factors on heart rate variability","volume":"17","author":"Tiwari","year":"2021","journal-title":"Curr Cardiol Rev"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"e27487","DOI":"10.2196\/27487","article-title":"Accuracy assessment of Oura ring nocturnal heart rate and heart rate variability in comparison with electrocardiography in time and frequency domains: comprehensive analysis","volume":"24","author":"Cao","year":"2022","journal-title":"J Med Internet Res"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1080\/09638288.2019.1641848","article-title":"Understanding the psychosocial impact of joint hypermobility syndrome and Ehlers\u2013Danlos syndrome hypermobility type: a qualitative interview study","volume":"43","author":"Bennett","year":"2019","journal-title":"Disabil Rehabil"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1080\/09638288.2023.2176554","article-title":"Healthcare experiences among adults with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder in the United States","volume":"46","author":"Estrella","year":"2024","journal-title":"Disabil Rehabil"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"e0255894","DOI":"10.1371\/journal.pone.0255894","article-title":"The effect of age on the heart rate variability of healthy subjects","volume":"16","author":"Garavaglia","year":"2021","journal-title":"PLoS One"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1111\/j.1365-2982.2010.01493.x","article-title":"Gastrointestinal-specific anxiety: an important factor for severity of GI symptoms and quality of life in IBS","volume":"22","author":"Jerndal","year":"2010","journal-title":"Neurogastroenterol Motil"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"436","DOI":"10.7326\/0003-4819-118-6-199303150-00008","article-title":"Heart rate variability","volume":"118","author":"van Ravenswaaij-Arts","year":"1993","journal-title":"Ann Intern Med"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"3571","DOI":"10.3390\/s21103571","article-title":"Wrist-based Photoplethysmography assessment of heart rate and heart rate variability: validation of WHOOP","volume":"21","author":"Bellenger","year":"2021","journal-title":"Sensors"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"2631","DOI":"10.1080\/02640414.2020.1797448","article-title":"A validation study of the WHOOP strap against polysomnography to assess sleep","volume":"38","author":"Miller","year":"2020","journal-title":"J Sports Sci"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.3389\/fpsyg.2014.01040","article-title":"A healthy heart is not a metronome: an integrative review of the heart\u2019s anatomy and heart rate variability","volume":"5","author":"Shaffer","year":"2014","journal-title":"Front Psychol"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"187","DOI":"10.3109\/00048679809062728","article-title":"The relationship between psychiatric illness and the circadian pattern of heart rate","volume":"32","author":"Stampfer","year":"1998","journal-title":"Aust N Z J Psychiatry"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2147\/CPT.S43623","article-title":"Variations in circadian heart rate in psychiatric disorders: theoretical and practical implications","volume":"3","author":"Stampfer","year":"2013","journal-title":"ChronoPhysiol Ther"},{"key":"ref60","article-title":"Neurocardiology","volume-title":"Anatomical and functional principles","author":"Armour","year":"2003"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/S1095-6433(99)00137-3","article-title":"Understanding autonomic sympathovagal balance from short-term heart rate variations. Are we analyzing noise?","volume":"124","author":"Altimiras","year":"1999","journal-title":"Comp Biochem Physiol A Mol Integr Physiol"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"5231","DOI":"10.1080\/09638288.2021.1933618","article-title":"Developing a self-management intervention to manage hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS): an analysis informed by behaviour change theory","volume":"44","author":"Bennett","year":"2022","journal-title":"Disabil Rehabil"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1499582\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T20:10:39Z","timestamp":1736971839000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1499582\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":62,"alternative-id":["10.3389\/fneur.2024.1499582"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2024.1499582","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]},"article-number":"1499582"}}