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Related Experiment Video

Updated: Jun 12, 2026

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
07:02

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development

Published on: February 11, 2019

PRBS Gas Challenges Reveal Impaired Chemoreflex and Cholinergic Dynamics in MCI.

Suhaib Hashem1, Stanley Yamashiro2, Elizabeth Joe3

  • 1Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, USA. shashem@usc.edu.

Annals of Biomedical Engineering
|June 10, 2026
PubMed
Summary

Individuals with mild cognitive impairment (MCI) exhibit impaired cerebrovascular control, particularly in neurovascular coupling and baroreflex sensitivity, as revealed by a novel gas challenge. This study highlights subtle deficits in cerebral oxygenation regulation in early cognitive decline.

Keywords:
Alzheimer’s diseaseCerebral autoregulationChemoreflex sensitivityMild cognitive impairment (MCI)Principal dynamic mode (PDM)Pseudorandom binary sequence (PRBS)

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Last Updated: Jun 12, 2026

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Area of Science:

  • Neuroscience
  • Physiology
  • Medical Imaging

Background:

  • Mild cognitive impairment (MCI) is associated with cerebrovascular dysfunction.
  • Traditional assessments may miss subtle, frequency-dependent changes in cerebrovascular control.

Purpose of the Study:

  • To investigate dynamic cerebral oxygenation regulation in MCI versus healthy controls.
  • To uncover latent cerebrovascular deficits using broadband gas challenges and advanced modeling.

Main Methods:

  • Utilized a novel pseudorandom binary sequence (PRBS) gas challenge (hypoxia and hypercapnia).
  • Recorded cerebral oxygenation (TOI), arterial pressure (ABP), and end-tidal CO2 (PETCO2).
  • Applied Laguerre-based Volterra modeling and Principal Dynamic Mode (PDM) decomposition.

Main Results:

  • Healthy controls showed increased ventilation and TOI; MCI participants did not.
  • Cerebrovascular control differed significantly between groups, with MCI showing impaired responses.
  • PDM analysis indicated impaired baroreflex, chemoreflex, and neurovascular coupling in MCI.

Conclusions:

  • PRBS gas modulation and dynamic modeling reveal subtle cerebrovascular impairments in MCI.
  • This methodology offers mechanistic insights into early MCI pathophysiology.
  • The approach may aid in developing new physiomarkers for early detection.