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Longitudinal Awake Mouse fMRI During Voluntary Locomotion Using Zero TE Imaging and a Novel Treadmill Training
Lauren Daley1, Wen-Ju Pan1, Gopinath Kaundinya2
1Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Magnetic Resonance in Medicine
|January 8, 2026
Summary
Researchers developed a new awake rodent functional MRI (fMRI) protocol. This method allows studying brain activity during natural locomotion with minimal motion and stress, setting a new benchmark for rodent fMRI research.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Animal Models
Background:
- Anesthesia in rodent functional MRI (fMRI) limits the study of natural behaviors like locomotion.
- Standard echo planar imaging (EPI) is sensitive to motion, posing challenges for awake fMRI.
- Zero echo time (TE) sequences offer a potential solution for motion-sensitive fMRI.
Purpose of the Study:
- To establish a robust and reproducible protocol for longitudinal fMRI in awake, spontaneously locomoting mice.
- To investigate brain activity and functional connectivity during natural behavior without anesthesia.
- To address the challenge of motion artifacts in awake rodent fMRI.
Main Methods:
- Utilized an implanted headpiece, incremental training, and a custom treadmill for controlled locomotion.
- Employed zero TE fMRI sequences to minimize motion sensitivity.
- Incorporated reinforcement learning to facilitate subject training and adaptation.
- Collected data from 10 trained mice across multiple scanning sessions.
Main Results:
- Achieved minimal head motion during fMRI scans, comparable to anesthetized EPI.
- Observed consistent resting-state functional connectivity across subjects and sessions.
- Demonstrated minimal stress responses and comparable signal quality during locomotion versus rest.
- Identified altered functional connectivity and spatiotemporal dynamics during locomotion.
Conclusions:
- This study establishes a new benchmark for awake rodent fMRI.
- Enables direct investigation of whole-brain correlates of naturalistic behaviors like locomotion.
- Provides a valuable tool for studying brain function without confounding effects of anesthesia or excessive restraint.
