Improving reproducibility of motor evoked potentials in mice

Background: In preclinical research involving murine models of neurological diseases, Motor Evoked Potentials (MEPs) can detect pathological alterations in nerve conduction throughout the cortico-spinal tract. In mice, MEPs elicited by electrical stimulation of the motor cortex can be performed with epicranial or subdermal electrodes such as implanted screws or removable needles, which are associated with invasive surgery and variability in placement of the stimulating electrodes, respectively.Methods: We compared MEPs induced by epicranial or subcutaneous stimulation with a non-invasive surface cup electrode over five recording sessions, in healthy C57BL/6 mice. Additionally, using surface stimulation, we examined the recordings obtained with intramuscular needles or surface electrodes to understand if MEP reproducibility could be improved.Results: Resting motor threshold (RMT), MEP latency and amplitude were comparable among the different stimulation methods. Epicranial, subcutaneous and surface stimulation techniques presented good repeatability over time, with surface stimulation showing a significantly reduced inter-session variability. Compared with intramuscular needles, MEPs recorded with surface electrode showed reduced peak-to-peak amplitude at all timepoints. RMT and MEP latency were comparable with both recording methods. On the other hand, amplitudes recorded with the surface electrode presented a significantly lower inter-session variance, resulting in improved repeatability.Conclusion: Overall, there is evidence for highly reproducible results using different stimulating methods, with indication for reduced inter-session variability for surface stimulation. Moreover, MEP recording with surface electrode provided a decrease in amplitude variability over time, indicating improved measurement stability when considering amplitude as functional outcome in longitudinal studies.