Low-dose ketamine tilts the cortical excitation--inhibition balance irrespective of systemic physiological response
- 1University of Luebeck
Abstract
Non-invasive proxies of cortical excitation--inhibition (E:I) balance, are increasingly used to understand human neural dynamics; especially so the aperiodic (1/f) electroencephalographic (EEG) exponent. Ketamine, an NMDA-receptor antagonist, is thought to shift this balance toward excitation. Propofol, a GABAA-receptor agonist, should behave oppositely. Here we show that these pharmacological manipulations at low doses tilt the noninvasive read-out of E:I balance as predicted, and we demonstrate this effect to be robust against potential mediation by the ketamine-related systemic cardiovascular response. In a single-blind, placebo-controlled crossover study, 25 healthy adults received low, subanesthetic doses of ketamine, propofol, or placebo by target-controlled infusion during resting-state EEG. We further analyzed electrocardiogram (ECG) and dissociating ratings. Ketamine flattened the aperiodic exponent (i.e., a shift toward excitation) and raised heart rate and blood pressure; propofol exerted its effects in the opposite direction, while both agents reduced alpha oscillatory power. Critically, the cardiovascular response did not mediate the cortical E:I shift. Controlling for heart rate left the ketamine effect not only intact but numerically stronger, suggesting that E:I balance findings might even be underestimated when ignoring the systemic physiological response.
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BibTeX
@misc{kunze2026lowdose,
title = {{Low-dose ketamine tilts the cortical excitation--inhibition balance irrespective of systemic physiological response}},
author = {J. Kunze and J. P. Student and S. Tune and H. Oster and S. Schmidt and H. Ihmsen and A. Tzabazis and B. Lorenz and C. Nau and J. Obleser},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.17.752361},
url = {https://www.biorxiv.org/content/10.64898/2026.09.17.752361v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Low-dose ketamine tilts the cortical excitation--inhibition balance irrespective of systemic physiological response
AU - J. Kunze
AU - J. P. Student
AU - S. Tune
AU - H. Oster
AU - S. Schmidt
AU - H. Ihmsen
AU - A. Tzabazis
AU - B. Lorenz
AU - C. Nau
AU - J. Obleser
PY - 2026
DA - 2026/09/17
PB - bioRxiv
DO - 10.64898/2026.09.17.752361
UR - https://www.biorxiv.org/content/10.64898/2026.09.17.752361v1
AB - Non-invasive proxies of cortical excitation--inhibition (E:I) balance, are increasingly used to understand human neural dynamics; especially so the aperiodic (1/f) electroencephalographic (EEG) exponent. Ketamine, an NMDA-receptor antagonist, is thought to shift this balance toward excitation. Propofol, a GABAA-receptor agonist, should behave oppositely. Here we show that these pharmacological manipulations at low doses tilt the noninvasive read-out of E:I balance as predicted, and we demonstrate this effect to be robust against potential mediation by the ketamine-related systemic cardiovascular response. In a single-blind, placebo-controlled crossover study, 25 healthy adults received low, subanesthetic doses of ketamine, propofol, or placebo by target-controlled infusion during resting-state EEG. We further analyzed electrocardiogram (ECG) and dissociating ratings. Ketamine flattened the aperiodic exponent (i.e., a shift toward excitation) and raised heart rate and blood pressure; propofol exerted its effects in the opposite direction, while both agents reduced alpha oscillatory power. Critically, the cardiovascular response did not mediate the cortical E:I shift. Controlling for heart rate left the ketamine effect not only intact but numerically stronger, suggesting that E:I balance findings might even be underestimated when ignoring the systemic physiological response.
ER -