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Traditional assessments often overlook frequency-dependent features of cerebrovascular control; this work aims to uncover latent deficits through broadband perturbations and nonparametric dynamic modeling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Seventeen ApoE4-negative participants (9 controls, 8 MCI) underwent a three-session supine protocol involving PRBS-modulated inhalation of hypoxic and hypercapnic gas mixtures. Physiological signals\u2014including near-infrared spectroscopy (TOI), arterial pressure (ABP), and end-tidal CO\n                      <jats:sub>2<\/jats:sub>\n                      (PETCO\n                      <jats:sub>2<\/jats:sub>\n                      )\u2014were recorded. Laguerre-based Volterra modeling and Principal Dynamic Mode (PDM) decomposition were used to analyze the dynamic response of cerebral oxygenation to ABP and CO\n                      <jats:sub>2<\/jats:sub>\n                      stimuli. Group differences were statistically assessed using Welch\u2019s\n                      <jats:italic>t<\/jats:italic>\n                      -tests and repeated measures ANOVA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Controls showed significant increases in ventilation and TOI from baseline to stimulation (\n                      <jats:inline-formula>\n                        <jats:alternatives>\n                          <jats:tex-math>$$p &lt; 0.01$$<\/jats:tex-math>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                            <mml:mrow>\n                              <mml:mi>p<\/mml:mi>\n                              <mml:mo>&lt;<\/mml:mo>\n                              <mml:mn>0.01<\/mml:mn>\n                            <\/mml:mrow>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      ), while MCI did not. Gain of the first CO\n                      <jats:sub>2<\/jats:sub>\n                      PDM increased in controls during PRBS (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.016) but decreased in MCI. A low-frequency ABP-derived PDM (\n                      <jats:inline-formula>\n                        <jats:alternatives>\n                          <jats:tex-math>$$\\sim$$<\/jats:tex-math>\n                          <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                            <mml:mo>\u223c<\/mml:mo>\n                          <\/mml:math>\n                        <\/jats:alternatives>\n                      <\/jats:inline-formula>\n                      \u00a00.014\u00a0Hz), consistent with endothelial-dependent vasodilation, was elevated only in controls during stimulation. Persistent differences in spectral recovery, kernel profiles, and PDM Gains suggested impaired baroreflex and chemoreflex regulation, and possible disruption of cholinergic-linked neurovascular coupling in MCI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PRBS gas modulation combined with dynamic modeling revealed subtle but significant cerebrovascular control impairments in MCI. This methodology enables mechanistic insights into early pathophysiology and may aid future physiomarker development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10439-026-04213-7","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:04:40Z","timestamp":1781100280000},"page":"2497-2507","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PRBS Gas Challenges Reveal Impaired Chemoreflex and Cholinergic Dynamics in MCI"],"prefix":"10.1007","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3420-7242","authenticated-orcid":false,"given":"Suhaib","family":"Hashem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Yamashiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Joe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Chui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilis","family":"Marmarelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"issue":"2","key":"4213_CR1","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1113\/jphysiol.1971.sp009525","volume":"216","author":"JD Bristow","year":"1971","unstructured":"Bristow, J. 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