Identification and verification of a 'true' TMS evoked potential in TMS-EEG

The concurrent combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) can unveil functional neural mechanisms with applications in basic and clinical research. In particular, TMS-evoked potentials (TEPs) potentially allow studying excitability and connectivity of the cortex in a causal manner that is not easily or non-invasively attainable with other neuroimaging techniques. The TEP waveform is obtained by isolating the EEG responses phase-locked to the time of TMS application. The intended component in a TEP waveform is the cortical activation by the TMS-induced electric current, free of instrumental and physiological artifact sources. This artifact-free cortical activation can be referred to as 'true' TEP. However, due to many unwanted auxiliary effects of TMS, the interpretation of 'true' TEPs has not been free of controversy. This paper reviews the most recent understandings of 'true' TEPs and their application. In the first part of the paper, TEP components are defined according to recommended methodologies. In the second part, the verification of 'true' TEP is discussed along with its sensitivity to brain-state, age, and disease. The various proposed origins of TEP components are then presented in the context of existing literature. Throughout the paper, lessons learned from the past TMS-EEG studies are highlighted to guide the identification and interpretation of 'true' TEPs in future studies.