{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:00:53Z","timestamp":1785402053295,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,29]]},"group-title":"Neuroscience","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["7DP2NS136872-02"],"award-info":[{"award-number":["7DP2NS136872-02"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Electrical stimulation is widely used to evoke artificial sensation, yet how temporal stimulation patterns are transformed into neural activity and perception remains poorly understood. Recent behavioral studies have shown that increasing the aperiodicity of spinal cord stimulation pulse trains alters both detection thresholds and discrimination performance despite constant pulse counts, suggesting a role for temporal structure beyond rate alone. However, the neural mechanisms underlying these effects remain unresolved.<\/jats:p>\n                <jats:p>We developed a biophysically grounded computational framework linking a finite-element model of the rodent spinal cord, conductance-based axon simulations, and observer decision models to investigate how stimulation periodicity shapes neural responses and resulting behavior. By systematically varying stimulation amplitude, frequency, and inter-pulse interval variability, we identified distinct spike-count regimes arising from interactions between stimulation timing and axonal membrane dynamics. These regimes ranged from single spikes and small volleys to sustained spike trains, and they exhibited diverse frequency- and variability-dependent trends.<\/jats:p>\n                <jats:p>No single regime was able to sufficiently explain experimentally observed detection threshold trends; instead, mixtures of regimes accurately reproduced both frequency-dependent threshold behavior and trial-level variability. Extending this framework to periodicity discrimination, we show that features derived from regime mixtures contain sufficient information to recover behavioral psychometric curves. Furthermore, observer model results provide a mechanistic account of behavioral asymmetries depending on the periodicity of the reference stimulus: discrimination relative to periodic inputs relied on combined rate and timing evidence, whereas discrimination relative to aperiodic inputs was dominated by timing irregularity.<\/jats:p>\n                <jats:p>These results establish a mechanistic link between stimulation temporal structure, axonal spike generation, and perceptual behavior. This framework suggests that spinal cord stimulation does not operate within a single fixed neural regime but instead engages a spectrum of spike-count regimes whose mixtures shape perception. These findings have important implications for the design of biomimetic stimulation strategies, highlighting temporal patterning as a key dimension for controlling sensory outcomes.<\/jats:p>","DOI":"10.64898\/2026.04.25.720749","type":"posted-content","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T10:05:15Z","timestamp":1777457115000},"source":"Crossref","is-referenced-by-count":0,"title":["Axonal spike-count regimes link spinal cord stimulation periodicity to artificial sensory detection and discrimination in rodents"],"prefix":"10.64898","author":[{"given":"Taylor J.","family":"Tvrdy","sequence":"first","affiliation":[{"name":"Lampe Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA"},{"name":"UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biological Intelligence, Seewiesen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Radhakrishna","sequence":"additional","affiliation":[{"name":"Lampe Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob C.","family":"Slack","sequence":"additional","affiliation":[{"name":"Lampe Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4913-8006","authenticated-orcid":false,"given":"Amol P.","family":"Yadav","sequence":"additional","affiliation":[{"name":"Lampe Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC, USA"},{"name":"UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"name":"UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA"},{"name":"UNC Neurosurgery, School of Medicine, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026050204100801000_2026.04.25.720749v1.1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1491-06.2006"},{"issue":"4","key":"2026050204100801000_2026.04.25.720749v1.2","first-page":"443","article-title":"Restoration of sensory information via bionic hands. Nat","volume":"7","year":"2023","journal-title":"Biomed. Eng"},{"key":"2026050204100801000_2026.04.25.720749v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.04.011"},{"key":"2026050204100801000_2026.04.25.720749v1.4","doi-asserted-by":"publisher","DOI":"10.1109\/TNSRE.2019.2936739"},{"key":"2026050204100801000_2026.04.25.720749v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4598(199802)21:2<137::AID-MUS1>3.0.CO;2-C"},{"issue":"2","key":"2026050204100801000_2026.04.25.720749v1.6","doi-asserted-by":"crossref","first-page":"026024","DOI":"10.1088\/1741-2552\/aaa87a","article-title":"Advantages of soft subdural implants for the delivery of electrochemical neuromodulation therapies to the spinal cord","volume":"15","year":"2018","journal-title":"J. Neural Eng"},{"key":"2026050204100801000_2026.04.25.720749v1.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1688-13.2013"},{"key":"2026050204100801000_2026.04.25.720749v1.8","doi-asserted-by":"publisher","DOI":"10.1101\/2025.08.19.25330198"},{"key":"2026050204100801000_2026.04.25.720749v1.9","unstructured":"COMSOL, Inc. (n.d.). COMSOL Multiphysics v. 6.2. COMSOL AB. Retrieved https:\/\/www.comsol.com"},{"key":"2026050204100801000_2026.04.25.720749v1.10","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2767-14.2014"},{"key":"2026050204100801000_2026.04.25.720749v1.11","doi-asserted-by":"publisher","DOI":"10.1080\/00223980.1959.9916336"},{"issue":"361","key":"2026050204100801000_2026.04.25.720749v1.12","first-page":"361 141","article-title":"Intracortical microstimulation of human somatosensory cortex","volume":"8","year":"2016","journal-title":"Sci. Transl. Med"},{"key":"2026050204100801000_2026.04.25.720749v1.13","first-page":"1","article-title":"Temporal pattern of electrical stimulation is a new dimension of therapeutic innovation","volume":"8","year":"2019","journal-title":"Curr Opin Biomed Eng"},{"key":"2026050204100801000_2026.04.25.720749v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/BF02368219"},{"issue":"5","key":"2026050204100801000_2026.04.25.720749v1.15","doi-asserted-by":"crossref","first-page":"1001558","DOI":"10.1371\/journal.pbio.1001558","article-title":"Multiplexing stimulus information through rate and temporal codes in primate somatosensory cortex","volume":"11","year":"2013","journal-title":"PLOS Biology"},{"key":"2026050204100801000_2026.04.25.720749v1.16","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.25.6.819"},{"key":"2026050204100801000_2026.04.25.720749v1.17","doi-asserted-by":"publisher","DOI":"10.1162\/neco.1997.9.6.1179"},{"key":"2026050204100801000_2026.04.25.720749v1.18","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1403.2002._2005.x"},{"issue":"3","key":"2026050204100801000_2026.04.25.720749v1.19","first-page":"161","article-title":"Review: Bioelectrical mechanisms in spinal cord stimulation","volume":"18","year":"2014","journal-title":"Neuromodulation"},{"key":"2026050204100801000_2026.04.25.720749v1.20","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41551-025-01583-6","article-title":"Neural mechanisms underlying intracortical microstimulation for sensory restoration","volume":"10","year":"2026","journal-title":"Nature Biomedical Engineering"},{"key":"2026050204100801000_2026.04.25.720749v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2023.05.013"},{"key":"2026050204100801000_2026.04.25.720749v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphysparis.2011.10.003"},{"key":"2026050204100801000_2026.04.25.720749v1.23","doi-asserted-by":"publisher","DOI":"10.1088\/1741-2552\/ab8344"},{"key":"2026050204100801000_2026.04.25.720749v1.24","unstructured":"Kiang, N. Y. S. , Watanabe, T. , Thomas, E. C. , & Clark, L. F. (1965). Discharge patterns of single fibers in the cat\u2019s auditory nerve."},{"key":"2026050204100801000_2026.04.25.720749v1.25","doi-asserted-by":"publisher","DOI":"10.1007\/BF02344716"},{"key":"2026050204100801000_2026.04.25.720749v1.26","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2161-12.2012"},{"key":"2026050204100801000_2026.04.25.720749v1.27","doi-asserted-by":"publisher","DOI":"10.1007\/s10827-016-0623-7"},{"key":"2026050204100801000_2026.04.25.720749v1.28","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00353.2001"},{"issue":"1","key":"2026050204100801000_2026.04.25.720749v1.29","doi-asserted-by":"crossref","first-page":"11737","DOI":"10.1038\/s41598-021-90661-1","article-title":"Temporal coherency of mechanical stimuli modulates tactile form perception","volume":"11","year":"2021","journal-title":"Scientific Reports"},{"issue":"3","key":"2026050204100801000_2026.04.25.720749v1.30","doi-asserted-by":"crossref","first-page":"1000025","DOI":"10.1371\/journal.pcbi.1000025","article-title":"Neural coding of natural stimuli: Information at sub-millisecond resolution","volume":"4","year":"2008","journal-title":"PLoS Comput. Biol"},{"key":"2026050204100801000_2026.04.25.720749v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/341052a0"},{"key":"2026050204100801000_2026.04.25.720749v1.32","doi-asserted-by":"crossref","unstructured":"Ng, K. K. W. , Birznieks, I. , Tse, I. T. H. , Andersen, J. , Nilsson, S. , & Vickery, R. M . (2018). Perceived frequency of aperiodic vibrotactile stimuli depends on temporal encoding. Haptics: Science, Technology, and Applications.","DOI":"10.1007\/978-3-319-93445-7_18"},{"key":"2026050204100801000_2026.04.25.720749v1.33","doi-asserted-by":"publisher","DOI":"10.1109\/TNSRE.2011.2166807"},{"key":"2026050204100801000_2026.04.25.720749v1.34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.21.1.227"},{"key":"2026050204100801000_2026.04.25.720749v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00330-3"},{"key":"2026050204100801000_2026.04.25.720749v1.36","doi-asserted-by":"crossref","first-page":"32904","DOI":"10.7554\/eLife.32904","article-title":"Proprioceptive and cutaneous sensations in humans elicited by intracortical microstimulation","volume":"7","year":"2018","journal-title":"eLife"},{"key":"2026050204100801000_2026.04.25.720749v1.37","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00829.2003"},{"key":"2026050204100801000_2026.04.25.720749v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/J.JNEUMETH.2018.02.009"},{"key":"2026050204100801000_2026.04.25.720749v1.39","unstructured":"Shapr3D, Zrt. (n.d.). Shapr 3D CAD modeling. Retrieved https:\/\/www.shapr3d.com"},{"issue":"4","key":"2026050204100801000_2026.04.25.720749v1.40","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1152\/jn.00284.2022","article-title":"Perceived tactile intensity at a fixed primary afferent spike rate varies with the temporal pattern of spikes","volume":"128","year":"2022","journal-title":"Journal of Neurophysiology"},{"key":"2026050204100801000_2026.04.25.720749v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.biosystems.2004.09.023"},{"key":"2026050204100801000_2026.04.25.720749v1.42","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.243.115"},{"issue":"2","key":"2026050204100801000_2026.04.25.720749v1.43","doi-asserted-by":"crossref","first-page":"026003","DOI":"10.1088\/1741-2552\/ad2b89","article-title":"The role of stimulus periodicity on spinal cord stimulation-induced artificial sensations in rodents","volume":"21","year":"2024","journal-title":"Journal of Neural Engineering"},{"key":"2026050204100801000_2026.04.25.720749v1.44","doi-asserted-by":"crossref","unstructured":"Vallbo, A. B. , & Johansson, R . (1976). Skin mechanoreceptors in the hand: Neural and psychophysical thresholds. Pergamon.","DOI":"10.1016\/B978-0-08-021208-1.50021-7"},{"key":"2026050204100801000_2026.04.25.720749v1.45","doi-asserted-by":"publisher","DOI":"10.1162\/089976601300014321"},{"key":"2026050204100801000_2026.04.25.720749v1.46","doi-asserted-by":"publisher","DOI":"10.1088\/0954-898X_8_2_003"},{"key":"2026050204100801000_2026.04.25.720749v1.47","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3699-06.2007"},{"key":"2026050204100801000_2026.04.25.720749v1.48","unstructured":"Watson, C. , Paxinos, G. , & Kayalioglu, G . (2009). The spinal cord: A Christopher and Dana Reeve Foundation text and atlas. Academic Press."},{"key":"2026050204100801000_2026.04.25.720749v1.49","unstructured":"Weber, E. H . (1834). De Pulsu, resorptione, auditu et tactu: Annotations anatomicae et physiologicae. CF Koehler."},{"issue":"4","key":"2026050204100801000_2026.04.25.720749v1.50","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.brs.2021.04.024","article-title":"Generating artificial sensations with spinal cord stimulation in primates and rodents","volume":"14","year":"2021","journal-title":"Brain Stimulation"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.25.720749","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T11:10:18Z","timestamp":1777720218000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.25.720749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":50,"URL":"https:\/\/doi.org\/10.64898\/2026.04.25.720749","relation":{},"subject":[],"published":{"date-parts":[[2026,4,29]]},"subtype":"preprint"}}