{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T19:36:06Z","timestamp":1788550566880,"version":"build-2803163510"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T00:00:00Z","timestamp":1657152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007165","name":"University of Missouri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Artif. Intell."],"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Cardiovascular dysautonomia may impact the quality of life and survival in amyotrophic lateral sclerosis (ALS). Such dysfunction is not systematically assessed in these patients. Wearable devices could help. The feasibility of a wearable biosensor to detect heart rate variability (HRV), a physiological marker of sympathovagal balance, was studied for the first time in real-world settings in ALS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Five ALS patients (two early\/three late; one bulbar-onset; mildly-to-moderately disabled) and five age\/sex\/BMI\/comorbidities-matched controls underwent assessment of 3-day HRV <jats:italic>via<\/jats:italic> VitalConnect biosensor (worn on the left thorax). De-identified data captured by the biosensor were transferred to a secure cloud server <jats:italic>via<\/jats:italic> a relay Bluetooth device. Baseline ALS severity\/anxiety and physical activity during testing were documented\/quantified. Time-domain HRV measures (i.e., pNN50) were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An overall 3-day abnormal HRV (pNN50 &amp;lt; 3%), was found in three out of five patients (mean \u00b1 SD for the group, 2.49 \u00b1 1.51). Similar changes were reported in controls (12.32 \u00b1 21.14%). There were no statistically significant relationships between pNN50 values and baseline anxiety or physical activity during the tested days (<jats:italic>p<\/jats:italic> &amp;gt; 0.05 for both groups). A negative correlation was found between pNN50 values and age in patients (<jats:italic>p<\/jats:italic> = 0.01) and controls (<jats:italic>p<\/jats:italic> = 0.09), which is similar with what is found in the general population. In line with prior studies, pNN50 values were independent of disease stage (<jats:italic>p<\/jats:italic> = 0.6) and disability (<jats:italic>p<\/jats:italic> = 0.4).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These preliminary results suggest that remote HRV measures using the VitalConnect is feasible and may constitute an improved strategy to provide insights into sympathovagal balance in ALS. Further work with larger sample sizes is warranted.<\/jats:p><\/jats:sec>","DOI":"10.3389\/frai.2022.910049","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T08:17:25Z","timestamp":1657181845000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Pilot Study of Real-World Monitoring of the Heart Rate Variability in Amyotrophic Lateral Sclerosis"],"prefix":"10.3389","volume":"5","author":[{"given":"Alexander A.","family":"Brown","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley J.","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vovanti","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce E.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin D.","family":"Pearre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ifeoma A.","family":"Anunoby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Q.","family":"Beversdorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Barohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen M.","family":"Cirstea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jns.2007.01.007","article-title":"Sympathetic disturbances increase risk of sudden cardiac arrest in sporadic ALS","volume":"254","author":"Asai","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1097\/01.wco.0000183114.76056.0e","article-title":"Autonomic impairment in amyotrophic lateral sclerosis","volume":"18","author":"Baltadzhieva","year":"2005","journal-title":"Curr. Opin. Neurol."},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-386525-0.00002-0","article-title":"\u201cCentral autonomic control,\u201d","volume-title":"Primer on the Autonomic Nervous System","author":"Benarroch","year":"2012"},{"key":"B4","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/0002-9149(88)90917-4","article-title":"Components of heart rate variability measured during healing of acute myocardial infarction","volume":"61","author":"Bigger","year":"1988","journal-title":"Am. J. Cardiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology","volume":"17","author":"Camm Aj","year":"1996","journal-title":"Eur. Heart J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/S0022-510X(99)00210-5","article-title":"The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III)","volume":"169","author":"Cedarbaum","year":"1999","journal-title":"J. Neurol. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"80","DOI":"10.3389\/fpsyt.2014.00080","article-title":"Anxiety disorders are associated with reduced heart rate variability: a meta-analysis","volume":"5","author":"Chalmers","year":"2014","journal-title":"Front. Psychiatry"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1161\/STROKEAHA.110.601047","article-title":"Primary motor cortex in stroke: a functional MRI-guided proton MR spectroscopic study","volume":"42","author":"Cirstea","year":"2011","journal-title":"Stroke"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1152\/jn.00329.2016","article-title":"Magnetic resonance spectroscopy of current hand amputees reveals evidence for neuronal-level changes in former sensorimotor cortex","volume":"117","author":"Cirstea","year":"2017","journal-title":"J. Neurophysiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1097\/PHM.0000000000000791","article-title":"Pre-therapy neural state of bilateral motor and premotor cortices predicts therapy gain after subcortical stroke: a pilot study","volume":"97","author":"Cirstea","year":"2018","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"B11","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1177\/1545968313516868","article-title":"Handgrip-related activation in the primary motor cortex relates to underlying neuronal metabolism after stroke","volume":"28","author":"Cirstea","year":"2014","journal-title":"Neurorehab. Neural. Repair."},{"key":"B12","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.brainres.2012.04.052","article-title":"Neuronal-glial alterations in non-primary motor areas in chronic subcortical stroke","volume":"1463","author":"Cirstea","year":"2012","journal-title":"Brain Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1161\/01.STR.0000173400.19346.bd","article-title":"Prognostic implications of right-sided insular damage, cardiac autonomic derangement, and arrhythmias after acute ischemic stroke","volume":"36","author":"Colivicchi","year":"2005","journal-title":"Stroke"},{"key":"B14","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.nicl.2018.05.020","article-title":"Cortical markers of cognitive syndromes in amyotrophic lateral sclerosis","volume":"19","author":"Consonni","year":"2018","journal-title":"Neuroimage Clin."},{"key":"B15","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1006\/nimg.1998.0395","article-title":"Cortical surface-based analysis. I. Segmentation and surface reconstruction","volume":"9","author":"Dale","year":"1999","journal-title":"Neuroimage"},{"key":"B16","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.neuroimage.2006.01.021","article-title":"An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest","volume":"31","author":"Desikan","year":"2006","journal-title":"Neuroimage"},{"key":"B17","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1007\/s00421-008-0800-0","article-title":"Effect of physical activity on heart rate variability in normal weight, overweight and obese subjects: results from the SAPALDIA study","volume":"104","author":"Felber Dietrich","year":"2008","journal-title":"Eur. J. Appl. Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1002\/aur.1646","article-title":"Psychophysiological associations with gastrointestinal symptomatology in autism spectrum disorder","volume":"10","author":"Ferguson","year":"2017","journal-title":"Autism Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.bbi.2016.05.009","article-title":"Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder","volume":"58","author":"Ferguson","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"B20","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1109\/42.906426","article-title":"Automated manifold surgery: constructing geometrically accurate and topologically correct models of the human cerebral cortex","volume":"20","author":"Fischl","year":"2001","journal-title":"IEEE Trans. Med. Imaging"},{"key":"B21","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1093\/cercor\/bhg087","article-title":"Automatically parcellating the human cerebral cortex","volume":"14","author":"Fischl","year":"2004","journal-title":"Cereb. Cortex"},{"key":"B22","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1177\/15459683211062889","article-title":"Greater and more natural use of the upper limbs during everyday life by former amputees versus prosthesis users","volume":"36","author":"Frey","year":"2022","journal-title":"Neurorehabil. Neural. Repair"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1152\/ajplegacy.1970.218.4.1030","article-title":"Cardiac vagal efferent activity and heart period in the carotid sinus reflex","volume":"218","author":"Katona","year":"1970","journal-title":"Am. J. Physiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/S0924-980X(98)00035-6","article-title":"Reduced baroreflex sensitivity and cardiorespiratory transfer in amyotrophic lateral sclerosis","volume":"109","author":"Linden","year":"1998","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1080\/03091902.2019.1640306","article-title":"A robust algorithm for heart rate variability time series artefact correction using novel beat classification","volume":"43","author":"Lipponen","year":"2019","journal-title":"J. Med. Eng. Technol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3109\/17482968.2011.584628","article-title":"Autonomic dysfunction in the early stage of ALS with bulbar involvement","volume":"12","author":"Merico","year":"2011","journal-title":"Amyotroph. Lateral. Scler."},{"key":"B27","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.jash.2010.05.001","article-title":"The insular cortex and cardiovascular system: a new insight into the brain-heart axis","volume":"4","author":"Nagai","year":"2010","journal-title":"J. Am. Soc. Hypertens."},{"key":"B28","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1002\/mus.10049","article-title":"Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis","volume":"25","author":"Oey","year":"2002","journal-title":"Muscle Nerve"},{"key":"B29","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/S1566-0702(01)00217-X","article-title":"Effect of tamsulosin hydrochloride on sympathetic hyperactivity in amyotrophic lateral sclerosis","volume":"88","author":"Ohno","year":"2001","journal-title":"Auton. Neurosci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1002\/cphy.c140076","article-title":"The insular cortex and the regulation of cardiac function","volume":"6","author":"Oppenheimer","year":"2016","journal-title":"Compr. Physiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"272","DOI":"10.3109\/17482960903390855","article-title":"Impairment of cardiac autonomic control in patients with amyotrophic lateral sclerosis","volume":"11","author":"Pavlovic","year":"2010","journal-title":"Amyotroph. Lateral. Scler."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.4187\/respcare.06681","article-title":"Decreased Heart Rate Variability in Individuals With Amyotrophic Lateral Sclerosis","volume":"64","author":"Pimentel","year":"2019","journal-title":"Respir. Care"},{"key":"B33","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1002\/mus.23313","article-title":"Decreased heart rate variability predicts death in amyotrophic lateral sclerosis","volume":"46","author":"Pinto","year":"2012","journal-title":"Muscle Nerve"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1111\/j.1540-8159.1996.tb03241.x","article-title":"Changes in heart rate variability with age","volume":"19","author":"Reardon","year":"1996","journal-title":"Pacing Clin. Electrophysiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1016\/j.neuroimage.2012.02.084","article-title":"Within-subject template estimation for unbiased longitudinal image analysis","volume":"61","author":"Reuter","year":"2012","journal-title":"Neuroimage"},{"key":"B36","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/0022-510X(94)90009-4","article-title":"Circulatory collapse and sudden death in respirator-dependent amyotrophic lateral sclerosis","volume":"124","author":"Shimizu","year":"1994","journal-title":"J. Neurol. Sci."},{"key":"B37","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/BF02291141","article-title":"Amyotrophic lateral sclerosis with hypertensive attacks: blood pressure changes in response to drug administration","volume":"6","author":"Shimizu","year":"1996","journal-title":"Clin. Auton. Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.jns.2004.08.006","article-title":"Chronological changes of sympathetic outflow to muscles in amyotrophic lateral sclerosis","volume":"227","author":"Shindo","year":"2004","journal-title":"J. Neurol. Sci."},{"key":"B39","volume-title":"Basic Neurochemistry: Molecular, Cellular and Medical Aspects.","author":"Siegel","year":"2005"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.1161\/CIRCULATIONAHA.113.005361","article-title":"Physical activity and heart rate variability in older adults: the Cardiovascular Health Study","volume":"129","author":"Soares-Miranda","year":"2014","journal-title":"Circulation"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2959","DOI":"10.1161\/STROKEAHA.116.014928","article-title":"Effect of right insular involvement on death and functional outcome after acute ischemic stroke in the IST-3 trial (third international stroke trial)","volume":"47","author":"Sposato","year":"2016","journal-title":"Stroke"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e006513","DOI":"10.1161\/CIRCHEARTFAILURE.119.006513","article-title":"Continuous wearable monitoring analytics predict heart failure hospitalization: the LINK-HF multicenter study","volume":"13","author":"Stehlik","year":"2020","journal-title":"Circ. Heart Fail."},{"key":"B43","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.cmpb.2013.07.024","article-title":"Kubios HRV\u2013heart rate variability analysis software","volume":"113","author":"Tarvainen","year":"2014","journal-title":"Comput. Methods Programs Biomed."},{"key":"B44","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/S0735-1097(97)00554-8","article-title":"Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades","volume":"31","author":"Umetani","year":"1998","journal-title":"J. Am. Coll. Cardiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e15471","DOI":"10.2196\/15471","article-title":"Continuous monitoring of vital signs in the general ward using wearable devices: randomized controlled trial","volume":"22","author":"Weenk","year":"2020","journal-title":"J. Med. Internet Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e91","DOI":"10.2196\/mhealth.7208","article-title":"Continuous monitoring of vital signs using wearable devices on the general ward: pilot study","volume":"5","author":"Weenk","year":"2017","journal-title":"JMIR Mhealth Uhealth"},{"key":"B47","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1080\/17482960701737716","article-title":"Neuronal loss associated with cognitive performance in amyotrophic lateral sclerosis: an (11C)-flumazenil PET study","volume":"9","author":"Wicks","year":"2008","journal-title":"Amyotroph. Lateral. Scler."},{"key":"B48","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/BF02267978","article-title":"Relationship between respiratory failure and plasma noradrenaline levels in amyotrophic lateral sclerosis","volume":"7","author":"Yamashita","year":"1997","journal-title":"Clin. Auton. Res."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1007\/s00213-015-4199-0","article-title":"Effects of propranolol on conversational reciprocity in autism spectrum disorder: a pilot, double-blind, single-dose psychopharmacological challenge study","volume":"233","author":"Zamzow","year":"2016","journal-title":"Psychopharmacology."},{"key":"B50","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1212\/WNL.30.1.98","article-title":"Norepinephrine and gamma-aminobutyric acid in amyotrophic lateral sclerosis","volume":"30","author":"Ziegler","year":"1980","journal-title":"Neurology"}],"container-title":["Frontiers in Artificial Intelligence"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frai.2022.910049\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T08:17:29Z","timestamp":1657181849000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/frai.2022.910049\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,7]]},"references-count":50,"alternative-id":["10.3389\/frai.2022.910049"],"URL":"https:\/\/doi.org\/10.3389\/frai.2022.910049","relation":{},"ISSN":["2624-8212"],"issn-type":[{"value":"2624-8212","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,7]]},"article-number":"910049"}}