{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:06:59Z","timestamp":1790197619028,"version":"4.1.0"},"reference-count":140,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Psychopharmacology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Scopolamine disrupts cholinergic mechanisms via nonspecific muscarinic antagonism. Centrally, excitatory neocortical innervations are antagonised causing spectral electroencephalography (EEG) changes and cognitive impairment. Peripherally, parasympathetic control of heart rate variability (HRV) is disrupted, although acute HRV effects of scopolamine are not well\u2010defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty adults with depression received scopolamine hydrobromide (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a024, 4\u20136\u00a0\u03bcg\/kg) or glycopyrronium bromide (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a016, 4\u20136\u00a0\u03bcg\/kg) infusions. Twelve healthy adults received scopolamine (4\u20136\u00a0\u03bcg\/kg) infusions. EEG and electrocardiography were recorded across 4\u00a0hours post\u2010infusion. EEG spectral, aperiodic, Lempel Ziv complexity (LZC), and microstates analyses were performed. Electrocardiographic HRV metric: proportion of high frequency power (pHF) was calculated and modelled via pharmacokinetic\u2010pharmacodynamic models to ascertain the HRV concentration\u2010effect relationship.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Scopolamine increased delta power between 0.5 and 3.5\u00a0h (at 35\u00a0min:\n                      <jats:italic>t<\/jats:italic>\n                      \u00a0=\u00a03.6,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.002). At 3\u00a0hours post\u2010infusion, scopolamine increased aperiodic slope (\n                      <jats:italic>t<\/jats:italic>\n                      \u00a0=\u00a0\u22123.4,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.047) and offset (\n                      <jats:italic>t<\/jats:italic>\n                      \u00a0=\u00a0\u22123.93,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.003) parameters, reduced LZC (\n                      <jats:italic>t<\/jats:italic>\n                      \u00a0=\u00a0\u22124.5,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a02\u00a0\u00d7\u00a010\n                      <jats:sup>\u22124<\/jats:sup>\n                      ), and microstate\n                      <jats:italic>D<\/jats:italic>\n                      mean duration (\n                      <jats:italic>t<\/jats:italic>\n                      \u00a0=\u00a0\u22123.0,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.039). EEG metrics correlated with drowsiness and alcohol\u2010like stimulant ratings. Peripherally, scopolamine reduced HRV, with two\u2010compartment pharmacokinetic models describing a delayed pHF effect via an effect compartment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These effects corresponded to increased drowsiness, reduced excitation\u2010inhibition ratio, and reduced HRV\u2014implicating central and peripheral muscarinic mechanisms reminiscent of Alzheimer's\u2010like cholinergic disruption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/anzctr.org.au\">anzctr.org.au<\/jats:ext-link>\n                      identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?id=377355%26isReview=true\">ACTRN12619000569101<\/jats:ext-link>\n                      and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?id=383504%26isClinicalTrial=False\">ACTRN12622000228785<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hup.70022","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T07:50:13Z","timestamp":1761119413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Scopolamine's Anticholinergic Effects on EEG Spectral, Aperiodic, Complexity, Microstates, and Heart Rate Variability"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4166-9814","authenticated-orcid":false,"given":"Joseph C. 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