Motor potentials evoked by transcranial magnetic stimulation: Interpreting a simple measure of a complex system.

Transcranial magnetic stimulation (TMS) is a non-invasive technique that is increasingly used to study the human brain. One of the principal outcome measures is the motor-evoked potential (MEP) elicited in a muscle following TMS over the primary motor cortex (M1), where it is used to estimate changes in corticospinal excitability. However, multiple elements play a role in MEP generation, so even apparently simple measures such as peak-to-peak amplitude have a complex interpretation. Here, we summarize what is currently known regarding the neural pathways and circuits that contribute to the MEP and discuss the factors that should be considered when interpreting MEP amplitude measured at rest, in the context of motor processing and patients with neurological conditions. In the last part of this work, we also discuss how emerging technological approaches can be combined with TMS to improve our understanding of neural substrates that can influence MEPs. Overall, this review aims to highlight the capabilities and limitations of TMS that are important to recognize when attempting to disentangle sources that contribute to the physiological state-related changes in corticomotor excitability. Abstract figure legend Transcranial magnetic stimulation (TMS) is a fundamental tool to noninvasively study the human brain. The motor-evoked potential (MEP) elicited in a muscle following TMS over the primary motor cortex (M1) is one of the most used measures for non-invasive quantification of cortical and spinal excitability in humans. However, given the multiple elements playing a role in MEP generation and modulation, its interpretation can be highly complex. This review summarizes what is currently known regarding the main cortical neurons, connections, and circuits contributing to modulations in MEP amplitudes, and we also discuss relevant concepts to be considered when interpreting MEPs measured across different brain states and patient populations. This article is protected by copyright. All rights reserved.