{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:10:36Z","timestamp":1793211036909,"version":"4.5.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"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. Neurol."],"abstract":"<jats:p>Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder in which motoneuron loss in the brain and spinal cord induces complex neuroplastic changes. Although these alterations hold considerable potential for clinical diagnosis and disease monitoring, they remain underutilized due to the lack of sensitive and non-invasive assessment methods. The H-reflex is a monosynaptic spinal reflex arc and represents the neurophysiological analog of the Achilles tendon reflex. A modified H-reflex double-stimulation paradigm enables differentiation of the temporal dynamics of spinal inhibitory and excitatory mechanisms. In ALS, this approach may provide clinically relevant insights into motor system dysfunction. Furthermore, this approach may contribute to a better understanding of the pathophysiology of spinal network plasticity associated with this disease, reflecting the complex interplay between spinal and supraspinal pathways. We assessed H-reflex recovery in 15 ALS patients and 82 non-ALS subjects, including 12 age-matched healthy controls (HC). The protocol included 14 interstimulus intervals (ISI) within a timeframe of up to one second. In contrast to the HCs, ALS patients exhibited recovery at ISIs of 30 or 50\u202fms. At interstimulus intervals ranging from 50 to 200\u202fms, the extent of recovery was significantly elevated in the ALS group compared to the age-matched HCs. ALS patients thus demonstrate heightened spinal network excitability as evidenced by an augmented and prematurely occurring H-reflex recovery measurement. These alterations likely reflect changes in neuronal network activity and can be attributed to modifications in both segmental spinal circuits and supraspinal regulatory pathways.<\/jats:p>","DOI":"10.3389\/fneur.2026.1790581","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:12:03Z","timestamp":1775707923000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Augmented and prematurely occurring H-reflex recovery curve shows enhanced spinal network excitability in ALS patients when employing the double stimulation paradigm"],"prefix":"10.3389","volume":"17","author":[{"given":"Sebastian A.","family":"W\u00f6lk","sequence":"first","affiliation":[{"name":"Oscar Langendorff Institute of Physiology, Rostock University Medical Center","place":["Rostock, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Prudlo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Rostock University Medical Center","place":["Rostock, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Neurology, Rostock University Medical Center","place":["Rostock, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Patejdl","sequence":"additional","affiliation":[{"name":"Department of Medicine, Health and Medical University Erfurt","place":["Erfurt, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","article-title":"Amyotrophic lateral sclerosis","volume":"400","author":"Feldman","year":"2022","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1016\/j.clinph.2020.04.005","article-title":"A proposal for new diagnostic criteria for ALS","volume":"131","author":"Shefner","year":"2020","journal-title":"Clin Neurophysiol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1136\/jnnp-2017-315574","article-title":"Fasciculation in amyotrophic lateral sclerosis: origin and pathophysiological relevance","volume":"88","author":"Carvalho","year":"2017","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref4","volume-title":"Hutchison's Clinical Methods","author":"Swash","year":"2002"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2643","DOI":"10.1016\/j.clinph.2016.04.025","article-title":"Assessment of the upper motor neuron in amyotrophic lateral sclerosis","volume":"127","author":"Huynh","year":"2016","journal-title":"Clin Neurophysiol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1111\/ene.12422","article-title":"Diagnostic utility of cortical excitability studies in amyotrophic lateral sclerosis","volume":"21","author":"Geevasinga","year":"2014","journal-title":"Eur J Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1136\/jnnp-2012-302315","article-title":"Why are upper motor neuron signs difficult to elicit in amyotrophic lateral sclerosis?","volume":"83","author":"Swash","year":"2012","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref8","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511545047","volume-title":"The Circuitry of the Human Spinal Cord","author":"Pierrot-Deseilligny","year":"2005"},{"key":"ref9","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9781139026727","volume-title":"The Circuitry of the Human Spinal Cord","author":"Pierrot-Deseilligny","year":"2012"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s00421-022-05119-7","article-title":"Revisiting the use of Hoffmann reflex in motor control research on humans","volume":"123","author":"Theodosiadou","year":"2023","journal-title":"Eur J Appl Physiol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jneumeth.2006.11.020","article-title":"Standardization of H-reflex analyses","volume":"162","author":"Brinkworth","year":"2007","journal-title":"J Neurosci Methods"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1016\/j.humov.2005.09.010","article-title":"A review of the H-reflex and M-wave in the human triceps surae","volume":"24","author":"Tucker","year":"2005","journal-title":"Hum Mov Sci"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/0013-4694(94)90132-5","article-title":"Central EMG and tests of motor control. Report of an IFCN committee","volume":"90","author":"Hallett","year":"1994","journal-title":"Electroencephalogr Clin Neurophysiol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/0006-8993(87)90832-8","article-title":"Recovery profile of single motoneurons after electrical stimuli in man","volume":"423","author":"Sabbahi","year":"1987","journal-title":"Brain Res"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1080\/146608200300079554","article-title":"An overview of H-reflex studies in amyotrophic lateral sclerosis","volume":"1","author":"Mazzini","year":"2000","journal-title":"Amyotroph Lateral Scler Other Motor Neuron Disord"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.gaitpost.2010.12.008","article-title":"Soleus H-reflex and its relation to static postural control","volume":"33","author":"Chen","year":"2011","journal-title":"Gait Posture"},{"key":"ref17","first-page":"401","article-title":"Assessing information of soleous and gastrocnemius motor unit H-reflex response to paired stimulation","volume":"44","author":"Sarmadi","year":"2004","journal-title":"Electromyogr Clin Neurophysiol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1080\/16501960310010142","article-title":"Changes in neuronal properties and spinal reflexes during development of spasticity following spinal cord lesions and stroke: studies in animal models and patients","volume":"35","author":"Hultborn","year":"2003","journal-title":"J Rehabil Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1111\/j.1748-1716.2006.01652.x","article-title":"The spinal pathophysiology of spasticity--from a basic science point of view","volume":"189","author":"Nielsen","year":"2007","journal-title":"Acta Physiol Oxf"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1136\/jnnp.33.3.358","article-title":"A critical review of evidence concerning long-loop reflexes excited by muscle afferents in man","volume":"33","author":"Gassel","year":"1970","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"106748","DOI":"10.1016\/j.nbd.2024.106748","article-title":"Impairments of inhibitory neurons in amyotrophic lateral sclerosis and frontotemporal dementia","volume":"203","author":"Lorenc","year":"2024","journal-title":"Neurobiol Dis"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2875","DOI":"10.1016\/j.clinph.2020.09.021","article-title":"Amyotrophic lateral sclerosis weakens spinal recurrent inhibition and post-activation depression","volume":"131","author":"\u00d6zyurt","year":"2020","journal-title":"Clin Neurophysiol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2148","DOI":"10.1212\/wnl.44.11.2148","article-title":"Recurrent inhibition is decreased in patients with amyotrophic lateral sclerosis","volume":"44","author":"Raynor","year":"1994","journal-title":"Neurology"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/0304-3940(85)90421-5","article-title":"Voluntary muscle release is not accompanied by H-reflex inhibition in patients with upper moto neuron lesions","volume":"61","author":"Schieppati","year":"1985","journal-title":"Neurosci Lett"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1002\/mus.28035","article-title":"Segmental motor neuron dysfunction in amyotrophic lateral sclerosis: insights from H reflex paradigms","volume":"69","author":"Castro","year":"2024","journal-title":"Muscle Nerve"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"107270","DOI":"10.1016\/j.nbd.2026.107270","article-title":"Afferent-driven modulation of spinal interneuron circuits across disease stages in amyotrophic lateral sclerosis","volume":"219","author":"Sangari","year":"2026","journal-title":"Neurobiol Dis"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1001\/archneur.1963.00460060021002","article-title":"The H reflex in normal, spastic, and rigid subjects","volume":"8","author":"Angle","year":"1962","journal-title":"Arch Neurol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1093\/brain\/95.3.559","article-title":"H reflexes in acute and chronic hemiplegia","volume":"95","author":"Garcia-Mullin","year":"1972","journal-title":"Brain"},{"key":"ref29","first-page":"285","article-title":"Reflex recovery curves in extrapyramidal disorders","volume":"14","author":"Sax","year":"1976","journal-title":"Adv Neurol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1136\/jnnp.32.1.21","article-title":"H reflex studies in patients with cerebellar disorders","volume":"32","author":"McLeod","year":"1969","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1093\/brain\/90.4.887","article-title":"Spinal segmental and long-loop reflexes on spinal motoneurone excitability in spasticity and rigidity","volume":"90","author":"Yap","year":"1967","journal-title":"Brain"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1097\/00004691-200206000-00008","article-title":"H-reflex recovery curves differentiate essential tremor, Parkinson's disease, and the combination of essential tremor and Parkinson's disease","volume":"19","author":"Sabbahi","year":"2002","journal-title":"J Clin Neurophysiol"},{"key":"ref33","first-page":"219","article-title":"Electrophysiological studies of reflex activity in patients with lesions of the nervous system. I. A comparison of spinal motoneurone excitability following afferent nerve volleys in normal persons and patients with upper motor neurone lesions","volume-title":"Bull Johns Hopkins Hosp","author":"Magladery","year":"1952"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1002\/mus.24579","article-title":"Influence of spinal cord lesion level and severity on H-reflex excitability and recovery curve","volume":"52","author":"Kumru","year":"2015","journal-title":"Muscle Nerve"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1097\/00002060-199509000-00007","article-title":"H-reflex recovery curve and reciprocal inhibition of H-reflex of the upper limbs in patients with spasticity secondary to stroke","volume":"74","author":"Panizza","year":"1995","journal-title":"Am J Phys Med Rehabil"},{"key":"ref36","first-page":"268","article-title":"The hoffmann reflex: methodologic considerations and applications for use in sports medicine and athletic training research","volume":"39","author":"Palmieri","year":"2004","journal-title":"J Athl Train"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"035010","DOI":"10.1088\/1361-6579\/abef56","article-title":"Onset detection in surface electromyographic signals across isometric explosive and ramped contractions: a comparison of computer-based methods","volume":"42","author":"Crotty","year":"2021","journal-title":"Physiol Meas"},{"key":"ref38","volume-title":"Statistical power Analysis for the Behavioral Sciences","author":"Cohen","year":"1988"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jshs.2012.02.002","article-title":"Sadly, the earth is still round (p < 0.05)","volume":"1","author":"Zhu","year":"2012","journal-title":"J Sport Health Sci"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1002\/1097-0142(1950)3:1<32:AID-CNCR2820030106>3.0.CO;2-3","article-title":"Index for rating diagnostic tests","volume":"3","author":"Youden","year":"1950","journal-title":"Cancer"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1113\/jphysiol.1981.sp013799","article-title":"Patterns of recurrent excitation and mutual inhibition of cat Renshaw cells","volume":"316","author":"Ryall","year":"1981","journal-title":"J Physiol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1113\/jphysiol.2011.204891","article-title":"Motoneuron afterhyperpolarisation duration in amyotrophic lateral sclerosis","volume":"589","author":"Piotrkiewicz","year":"2011","journal-title":"J Physiol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s002210050721","article-title":"Comparison of the depression of H-reflexes following previous activation in upper and lower limb muscles in human subjects","volume":"126","author":"Rossi-Durand","year":"1999","journal-title":"Exp Brain Res"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1007\/BF00227268","article-title":"On the mechanism of the post-activation depression of the H-reflex in human subjects","volume":"108","author":"Hultborn","year":"1996","journal-title":"Exp Brain Res"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.bj.2019.07.007","article-title":"Novel human models for elucidating mechanisms of rate-sensitive H-reflex depression","volume":"43","author":"Chang","year":"2020","journal-title":"Biom J"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1093\/brain\/123.8.1688","article-title":"Presynaptic inhibition and homosynaptic depression: a comparison between lower and upper limbs in normal human subjects and patients with hemiplegia","volume":"123","author":"Aymard","year":"2000","journal-title":"Brain"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"e20191734","DOI":"10.1084\/jem.20191734","article-title":"Synaptic restoration by cAMP\/PKA drives activity-dependent neuroprotection to motoneurons in ALS","volume":"217","author":"B\u0105czyk","year":"2020","journal-title":"J Exp Med"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"eadk3229","DOI":"10.1126\/sciadv.adk3229","article-title":"Spinal inhibitory neurons degenerate before motor neurons and excitatory neurons in a mouse model of ALS","volume":"10","author":"Monta\u00f1ana-Rosell","year":"2024","journal-title":"Sci Adv"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"e13758","DOI":"10.1111\/apha.13758","article-title":"Transient increase in recurrent inhibition in amyotrophic lateral sclerosis as a putative protection from neurodegeneration","volume":"234","author":"Sangari","year":"2022","journal-title":"Acta Physiol"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"115046","DOI":"10.1016\/j.celrep.2024.115046","article-title":"Spinal microcircuits go through multiphasic homeostatic compensations in a mouse model of motoneuron degeneration","volume":"43","author":"Nascimento","year":"2024","journal-title":"Cell Rep"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"eadz5524","DOI":"10.1126\/sciadv.adz5524","article-title":"Personalized mapping of inhibitory spinal cord circuits in humans via noninvasive neural decoding and in silico modeling","volume":"11","author":"Pascual-Valdunciel","year":"2025","journal-title":"Sci Adv"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1152\/jn.00144.2024","article-title":"Synaptic dynamics linked to widespread elevation of H-reflex before peripheral denervation in amyotrophic lateral sclerosis","volume":"132","author":"Sangari","year":"2024","journal-title":"J Neurophysiol"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1002\/mus.880151009","article-title":"Nerve conduction studies in amyotrophic lateral sclerosis","volume":"15","author":"Cornblath","year":"1992","journal-title":"Muscle Nerve"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1113\/JP275498","article-title":"The vulnerability of spinal motoneurons and soma size plasticity in a mouse model of amyotrophic lateral sclerosis","volume":"596","author":"Dukkipati","year":"2018","journal-title":"J Physiol"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1152\/jn.1965.28.3.560","article-title":"Functional significance of cell size in spinale neurons","volume":"28","author":"Henneman","year":"1965","journal-title":"J Neurophysiol"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1093\/geronj\/37.1.24","article-title":"Age-related changes in monosynaptic reflex excitability","volume":"37","author":"Sabbahi","year":"1982","journal-title":"J Gerontol"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"2781","DOI":"10.1007\/s10072-023-06753-5","article-title":"Increasing prevalence 2015-2019 of amyotrophic lateral sclerosis in Sardinia, Italy","volume":"44","author":"Pateri","year":"2023","journal-title":"Neurol Sci"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1007\/s00421-025-05720-6","article-title":"Discussion on the validity of commonly used reliability indices in sports medicine and exercise science: a critical review with data simulations","volume":"125","author":"Warneke","year":"2025","journal-title":"Eur J Appl Physiol"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/s0895-4356(00)00314-0","article-title":"Adjusting for multiple testing--when and how?","volume":"54","author":"Bender","year":"2001","journal-title":"J Clin Epidemiol"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1136\/bmj.316.7139.1236","article-title":"What's wrong with Bonferroni adjustments","volume":"316","author":"Perneger","year":"1998","journal-title":"BMJ"},{"key":"ref61","volume-title":"StatPearls: Modified Ashworth Scale","author":"Harb","year":"2022"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1002\/mus.24892","article-title":"Natural history of muscle cramps in amyotrophic lateral sclerosis","volume":"53","author":"Caress","year":"2016","journal-title":"Muscle Nerve"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1790581\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T04:12:08Z","timestamp":1775707928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1790581\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":62,"alternative-id":["10.3389\/fneur.2026.1790581"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1790581","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]},"article-number":"1790581"}}