Neuroscience Letters 478 (2010) 24–28 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet The relationship between peripheral and early cortical activation induced by transcranial magnetic stimulation Hanna Mäki a,b,∗ , Risto J. Ilmoniemi a,b a Department of Biomedical Engineering and Computational Science (BECS), Aalto University School of Science and Technology, Espoo, Finland b BioMag Laboratory, HUSLAB, Helsinki University Central Hospital, Helsinki, Finland article info Article history: Received 17 February 2010 Received in revised form 21 April 2010 Accepted 25 April 2010 Keywords: TMS–EEG Cortical excitability Motor evoked potential abstract The purpose of this study was to assess the relationship between peripheral muscle responses (motor evoked potentials, MEP) evoked by transcranial magnetic stimulation (TMS) and the early components of the TMS-evoked EEG response, both of which reflect cortical excitability. Left primary motor cortex of five healthy volunteers was stimulated with 100% of the motor threshold. The relationship between MEP amplitudes and the peak-to-peak amplitudes of the N15–P30 complex of the evoked EEG signal was determined at the single-trial level. MEP and N15–P30 amplitudes were significantly correlated in all five subjects. The results support the view that the amount of direct activation of neurons in M1 evoked by TMS affects both subsequent cortical activation and the activation of the target muscle. Cortical excitability is altered in some neuronal disorders and modulated locally during various tasks. It could thus be used as a marker of the state of health in many cases and as a method to study brain function. The present results improve our understanding of the early components of the TMS-evoked EEG signal, which reflect cortical excitability, and may thus have widespread use in clinical and scientific studies. © 2010 Elsevier Ireland Ltd. All rights reserved. Cortical excitability reflects the state of neurons. It is altered in many neuronal disorders, such as Alzheimer’s disease [1,7,9,30], multiple sclerosis [5], and Huntington’s disease [34], and modu- lated during various tasks [4,11,13,16,17,28]. Thus, it informs us both about the state of health and about information process- ing during a task; the excitability of each neuron depends on its instantaneous membrane potential [20]. Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) in com- bination with electromyographic (EMG) recording of the motor evoked potential (MEP) in the target muscle has been used to study corticospinal excitability [2]. Combining TMS with electroen- cephalography (EEG) has provided an effective tool for studying cortical excitability [14], allowing one to probe also areas other than M1 [6,12,22,26,31] and to use stimulation intensities below the threshold required to activate peripheral muscles [20,21]. In addition to the task-dependent or long-term fluctuations in cortical excitability, also the spontaneous moment-to-moment fluctuations are expected to affect the evoked responses. Indeed, MEPs elicited by identical consecutive stimuli vary largely in amplitude. Although part of the variability results from varying synchrony of the descending action potentials [24,32] and spinal excitability changes, also cortical excitability is believed to play a ∗ Corresponding author at: BECS, Aalto University, P.O. Box 12200, FI-00076 Aalto, Finland. Tel.: +358 50 344 3175; fax: +358 9 4702 3182. E-mail address: hanna.maki@hut.fi (H. Mäki). role [18,25,33,38]. It is a reasonable assumption that a stronger ini- tial TMS-induced excitatory activation of the cortex leads to both stronger subsequent activation of the cortex and stronger activa- tion of the target muscle. Thus, a correlation between MEP and evoked EEG signal can be expected even when stimulation strength is constant. Paus et al. [29] found a significant correlation between MEP amplitude and a negative deflection in the TMS-evoked EEG signal peaking around 100 ms after the pulse (N100), whereas in a study by Nikulin et al. [28], no relationship between MEP and N100 was found. However, the early deflections in the evoked EEG would serve as more direct measures for studying the excitability of the stimulated area. Particularly, as the conduction time between the brain and small hand muscles is about 20 ms, in case of M1 hand area stimulation the deflections peaking approximately 40 ms after the stimulus and later may be affected by the somatosen- sory feedback resulting from the target muscle activation. Bonato et al. [3] reported non-significant correlation coefficients r = 0.13 and 0.46 between the average amplitude of MEPs and the average amplitude of deflections peaking at 18 ms (N15; negativity over the stimulation site) and 28 ms (P30; widespread positivity), respec- tively, using the average values of five series of responses of all the six subjects averaged over trials and channels. To our knowl- edge, the correlation between MEPs and the early deflections of the TMS-evoked EEG response has not been studied at the single-trial level within subjects. Altogether, the early components of the TMS- evoked EEG response have not been studied extensively, partly because of the challenges in recording artefact-free signals imme- 0304-3940/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2010.04.059