{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T11:06:36Z","timestamp":1783940796402,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,9]]},"group-title":"Neurology","reference-count":19,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Deep brain stimulation (DBS) is a widely used therapy for neurologic and psychiatric disorders. Conventional DBS delivers highly regular stimulation patterns that suppress pathological activity but can induce stimulation-related side effects, limiting the therapeutic window. Introducing controlled temporal variability through stochastic pulse timing may represent an alternative programming dimension to improve tolerability while preserving clinical benefit.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>An adult in their 60\u2019s with bilateral Vim DBS underwent evaluation of tonic, pink-noise, and white-noise stimulation patterns delivered through his chronically implanted Boston Scientific Genus system using the Chronos research platform. We assessed tremor and stimulation-induced side effects using accelerometry, spiral drawing tasks, standardized speech recordings, and patient-reported paresthesias.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Pink noise stimulation preserved meaningful tremor suppression while improving tolerability compared with conventional tonic 130 Hz stimulation. Under tonic stimulation, dysarthria and paresthesias were prominent at 2.0 mA, narrowing the usable therapeutic window. In contrast, pink noise maintained tremor control across the same amplitude range with reduced side-effect burden. White noise stimulation demonstrated intermediate effects, providing improved tolerability relative to tonic stimulation but less tremor suppression than pink noise. Findings were consistent across accelerometry and functional drawing tasks.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This study provides first-in-human evidence that temporally structured stochastic pulse timing can preserve therapeutic benefit while expanding the tolerable stimulation range relative to tonic DBS. These findings suggest that temporal structure represents a clinically meaningful programming dimension that may broaden the DBS therapeutic window using software based updates to existing hardware. Further evaluation in larger cohorts is warranted.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.08.26357382","type":"posted-content","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T19:10:14Z","timestamp":1783624214000},"source":"Crossref","is-referenced-by-count":0,"title":["Cutting Through the Noise: Stochastic Pulse Timing for Deep Brain Stimulation"],"prefix":"10.64898","author":[{"given":"Matthew R","family":"Baker","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Mayo Clinic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemant","family":"Bokil","sequence":"additional","affiliation":[{"name":"Boston Scientific Corporation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soroush","family":"Niketeghad","sequence":"additional","affiliation":[{"name":"Boston Scientific Corporation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai J","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Mayo Clinic"},{"name":"Department of Biomedical Engineering and Physiology, Mayo Clinic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan T","family":"Klassen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071303250859000_2026.07.08.26357382v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/S41582-018-0128-2"},{"issue":"3","key":"2026071303250859000_2026.07.08.26357382v1.2","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.neubiorev.2007.06.003","article-title":"Mechanisms of action of deep brain stimulation (dbs)","volume":"32","year":"2008","journal-title":"Neuroscience Biobehavioral Reviews"},{"key":"2026071303250859000_2026.07.08.26357382v1.3","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13548"},{"issue":"S14","key":"2026071303250859000_2026.07.08.26357382v1.4","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/mds.20957","article-title":"Deep brain stimulation: postoperative issues","volume":"21","year":"2006","journal-title":"Movement disorders: official journal of the Movement Disorder Society"},{"issue":"7","key":"2026071303250859000_2026.07.08.26357382v1.5","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1136\/jnnp.2007.117507","article-title":"Pyramidal tract side effects induced by deep brain stimulation of the subthalamic nucleus. 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