TMS-EEG: first steps towards a clinical application in epilepsy

Abstract

With Transcranial Magnetic Stimulation (TMS) short magnetic pulses are applied to the cortex. The strength of the response to this stimulus can be used as a measure for the balance in excitation and inhibition. TMS is therefore of interest in the field of epilepsy. In this thesis we focus on the TMS evoked potential (TEP): the EEG response induced by TMS obtained after averaging over multiple single TMS pulses. As epilepsy is associated with a higher excitability, the TEP may be different in epilepsy patients. If so, the TEP could serve as a potential biomarker for epilepsy diagnostics, and as a monitoring tool for evaluating treatment efficacy. Two large amplitude artifacts hinder the evaluation of the TEP. Principal Component Analysis (PCA) applied on single TMS-EEG trials can be used to remove high amplitude components. Using PCA both artifacts are effectively reduced, thereby revealing the first TEP components and allowing further TEP analysis (chapter 2). TMS pulses are accompanied by a clicking sound, inducing an auditory evoked potential (AEP) which is superimposed to the TEP. This AEP can be minimized by using a headphone playing noise and with a layer of foam between the coil and head (chapter 3). Applying TMS-EEG to a completely deaf person proves that the TEP is definitely not only evoked by sound alone. For a clinical application of TMS-EEG, the variation of the TEP is of great importance. It appears that the variation between subjects is large, while the within subject variation of the TEP seems to be smaller. The motor threshold and motor evoked potential do not vary significantly during the day, and the TEP is highly reproducible at different TMS-EEG sessions during daytime (chapter 4). A study in a group of 14 epilepsy patients using anti-epileptic drugs showed a higher motor threshold and a larger amplitude of the TEP when compared to healthy controls (chapter 5). Part of these differences may possibly be explained by the use of AEDs.