BILATERAL CHANGES IN EXCITABILITY OF SENSORIMOTOR CORTICES DURING UNILATERAL MOVEMENT: COMBINED ELECTROENCEPHALOGRAPHIC AND TRANSCRANIAL MAGNETIC STIMULATION STUDY D. KIC ˇ IC ´ , a,b * P. LIOUMIS, a R. J. ILMONIEMI b AND V. V. NIKULIN c,d a BioMag Laboratory-HUSLAB, Helsinki University Central Hospital, P.O. Box 340, FI-00029 HUS, Helsinki, Finland. b Department of Biomedical Engineering and Computational Science, Helsinki University of Technology, Helsinki, Finland c Neurophysics Group, Department of Neurology, Campus Benjamin Franklin–Charité, University Medicine Berlin, Berlin, Germany d Bernstein Center for Computational Neuroscience, Berlin, Germany Abstract—It remains unclear what neuronal mechanisms in humans are reflected in the activation of the ipsilateral hemi- sphere during the performance of unilateral movements. To address this question we combined transcranial magnetic stimulation (TMS), electroencephalography (EEG), and elec- tromyographic (EMG) recordings of motor evoked potentials (MEPs). Compared with previous TMS studies, where changes in excitability might be related to both cortical and spinal mechanisms, our setup allowed a more direct evalua- tion of the cortical processes related to the performance of unilateral movements. EEG responses showed that the uni- lateral motor reactions were associated with the bilateral increase in the excitability of sensorimotor cortices. How- ever, this increase was smaller in the ipsilateral hemisphere most likely due to the fact that the excitation in ipsilateral hemisphere coincided with additional inhibitory processes related to the suppression of mirror movements. This expla- nation was further corroborated by showing that only con- tralateral changes in cortical excitability led to the increase in the amplitude of peripheral MEPs, while neuronal activation in the ipsilateral hemisphere was not associated with the changes in the muscle responses. These results suggest that the increased excitability in the ipsilateral hemisphere was uncoupled from the modulation of the cortico-spinal output. Moreover, we show that the background neuronal activity during unilateral movements was different in the ipsi- and contralateral hemisphere. This difference most likely reflects inter-hemispheric balance between the excitation and inhibi- tion which is required for the optimal performance of the unilateral movement. © 2008 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: unilateral movement, mirror movement, transcra- nial magnetic stimulation, electroencephalography. The present study explores neurophysiological correlates of unilateral movement in sensorimotor areas of both hemi- spheres, with a special emphasis on the role of the ipsilat- eral hemisphere. Functional imaging studies have demon- strated that unilateral movements are associated with ac- tivations in the ipsilateral sensorimotor cortex (Shibasaki and Nagae, 1984; Rao et al., 1993; Chen et al., 1997, 2002; Alkadhi et al., 2002; Kobayashi et al., 2003; Caramia et al., 2000; Kim et al., 2004). Measurements of move- ment-related magnetic fields have also shown a bilateral activation of motor areas at about 500 ms prior to self- paced movement (Kristeva et al., 1991; Salmelin et al., 1995; Tandonnet et al., 2003; Vidal et al., 2003). Previous studies with transcranial magnetic stimulation (TMS) have contradicting results showing that the cortical excitability in the ipsilateral hemisphere can be increased (Hoshiyama et al., 1996; Muellbacher et al., 2000; McMillan et al., 2004, 2006), decreased (Leocani et al., 2000; Duque et al., 2005; Koch et al., 2006) or not changed during the performance of unilateral movements (MacKinnon and Rothwell, 2000). It is possible that such different results could be related not only to the specific experimental tasks, but also to the fact that motor evoked potentials (MEPs), used in those stud- ies, reflect contribution of both cortical and spinal cord excitation which might have been differently mixed in each specific experiment. An advantage of our study is the combination of electroencephalography (EEG) and TMS, which allows a more direct evaluation of cortical excitability in both hemispheres during the preparation and execution of the unilateral movements. Apart from neurophysiological basis of unilateral move- ment organization, studying of ipsilateral activation might be also valuable in understanding the origins of mirror movements (MM, Cohen et al., 1991; Kristeva et al., 1991; Mayston et al., 1999; Verstynen et al., 2005; 2007). In general MMs have been hypothesized to occur either due to uncrossed cortico-spinal fibers (Konagaya et al., 1990; Cohen et al., 1991; Ziemann et al., 1999), branching of cortico-spinal axons innervating homologous “mirror” mus- cle (Hess et al., 1986; Tinazzi and Zanette, 1998; Stedman *Correspondence to: D. Kic ˇic ´, Department of Biomedical Engineering and Computational Science, Helsinki University of Technology, P.O. Box 3310, (Otakaari 7 B, 02150 Espoo) F1-02015 TKK, Helsinki, Finland. Tel: +358-9471-75582, +358-4077-07113, or +336-4363-2731; fax: +358- 9471-75781. E-mail address: dubravko.kicic@tkk.fi, dubravko@biomag.hus.fi or dkicic@gmail.com (D. Kic ˇic ´). Abbreviations: ANOVA, analysis of variance; APB, abductor pollicis brevis; CONTRA, contralateral movement; EEG, electroencephalog- raphy; EMG, electromyography; ER, evoked responses; IPSI, ipsilat- eral movement; MEP, motor evoked potential; MM, mirror movement; MRF, mesencephalic reticular formation; MT, motor threshold; NOMOV, no movement; p.h., post hoc; ROI, region of interest; RT, reaction time; TMS, transcranial magnetic stimulation; VIS, visual stimuli only; VISTMS, visual stimulus followed after 187 ms by a transcranial magnetic stimula- tion pulse. Neuroscience 152 (2008) 1119 –1129 0306-4522/08$32.00+0.00 © 2008 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.neuroscience.2008.01.043 1119