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Updated: May 3, 2026
Real-Time fMRI Brain Mapping in Animals
Published on: September 24, 2020
Specificity of stimulus-evoked fMRI responses in the mouse: the influence of systemic physiological changes
Aileen Schroeter1, Felix Schlegel1, Aline Seuwen2
1Institute for Biomedical Engineering, University and ETH Zurich, Wolfgang-Pauli-Str. 27, 8093 Zurich, Switzerland; Neuroscience Center Zurich, University and ETH Zurich, Winterthurer-Str. 190, 8057 Zurich, Switzerland.
Abstract:
Functional magnetic resonance (fMRI) in mice has become an attractive tool for mechanistic studies, for characterizing models of human disease, and for evaluation of novel therapies. Yet, controlling the physiological state of mice is challenging, but nevertheless important as changes in cardiovascular parameters might affect the hemodynamic readout which constitutes the basics of the fMRI signal. In contrast to rats, fMRI studies in mice report less robust brain activation of rather widespread character to innocuous sensory stimulation. Anesthesia is known to influence the characteristics of the fMRI signal. To evaluate modulatory effects imposed by the anesthesia on stimulus-evoked fMRI responses, we compared blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) signal changes to electrical hindpaw stimulation using the four commonly used anesthetics isoflurane, medetomidine, propofol and urethane. fMRI measurements were complemented by assessing systemic physiological parameters throughout the experiment. Unilateral stimulation of the hindpaw elicited widespread fMRI responses in the mouse brain displaying a bilateral pattern irrespective of the anesthetic used. Analysis of magnitude and temporal profile of BOLD and CBV signals indicated anesthesia-specific modulation of cerebral hemodynamic responses and differences observed for the four anesthetics could be largely explained by their known effects on animal physiology. Strikingly, independent of the anesthetic used our results reveal that fMRI responses are influenced by stimulus-induced cardiovascular changes, which indicate an arousal response, even to innocuous stimulation. This may mask specific fMRI signal associated to the stimulus. Hence, studying the processing of peripheral input in mice using fMRI techniques constitutes a major challenge and adapted paradigms and/or alternative fMRI readouts should also be considered when studying sensory processing in mice.
Insights
Anesthesia significantly impacts functional magnetic resonance imaging (fMRI) signals in mice by altering hemodynamic responses. Cardiovascular changes, even from mild stimuli, can mask true brain activity, posing challenges for sensory processing studies.
Area of Science:
- Neuroscience
- Physiology
- Medical Imaging
Background:
- Functional magnetic resonance imaging (fMRI) is valuable for studying mouse models of disease and testing therapies.
- Controlling physiological states in mice is crucial for accurate fMRI, as cardiovascular changes affect the signal.
- Mouse fMRI studies often show less robust and more widespread brain activation compared to rats.
Purpose of the Study:
- To evaluate how anesthesia modulates stimulus-evoked fMRI responses in mice.
- To compare blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) signals under different anesthetics.
- To understand the influence of anesthesia and physiological parameters on fMRI readouts.
Main Methods:
- Compared BOLD and CBV signals during electrical hindpaw stimulation under four anesthetics: isoflurane, medetomidine, propofol, and urethane.
- Monitored systemic physiological parameters throughout fMRI measurements.
- Analyzed the magnitude and temporal profile of fMRI responses.
Main Results:
- Hindpaw stimulation evoked widespread, bilateral fMRI responses regardless of anesthetic.
- Anesthetics specifically modulated cerebral hemodynamic responses, largely due to their physiological effects.
- Stimulus-induced cardiovascular changes, indicative of arousal, influenced fMRI responses, potentially masking stimulus-specific signals.
Conclusions:
- Anesthesia significantly alters fMRI signal characteristics in mice.
- Cardiovascular changes during fMRI experiments can confound results, especially in sensory processing studies.
- Adapted fMRI paradigms or alternative readouts are necessary for reliable mouse sensory processing research.
