Low-frequency rTMS over lateral premotor cortex induces lasting changes in regional activation and functional coupling of cortical motor areas Wei-Hung Chen a,b , Tatsuya Mima b , Hartwig R. Siebner b,c , Tatsuhide Oga b , Hidemi Hara b , Takeshi Satow b , Tahamina Begum b , Takashi Nagamine b , Hiroshi Shibasaki b, * a Department of Neurology, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan b Department of Brain Pathophysiology, Human Brain Research Center, Kyoto University Graduate School of Medicine, Shogoin, Sakyo, Kyoto, 606-8507, Japan c Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, University College of London, London, UK Accepted 25 February 2003 Abstract Objective: To study the effect of 0.9 Hz repetitive transcranial magnetic stimulation (rTMS) of the lateral premotor cortex on neuronal activity in cortical motor areas during simple motor tasks. Methods: In 8 subjects, electroencephalogram (EEG) and electromyogram (EMG) were simultaneously recorded during voluntary contractions of the thumb before and after a 15 min train of 0.9 Hz rTMS over the left lateral premotor cortex at stimulus intensity of 90% of active motor threshold. After-effects on cortical motor activity were assessed by measuring the task-related EEG power and inter-regional coherence changes, and the EEG – EMG coherence (EMGCoh). Results: Low-frequency rTMS over the premotor cortex gave rise to (i) a reduction of the task-related power decrease in the alpha and beta bands, (ii) a selective increase in the task-related coherence change among cortical motor areas in the upper alpha band, and (iii) a decrease in the cortico-muscular coherence. These effects lasted about 15 min after the end of rTMS intervention. Conclusions: The attenuated task-related power changes and decreased EMGCoh point to a lasting suppression of voluntary activation of cortical motor areas after rTMS. The present data provide an evidence for a transient reorganization of movement-related neuronal activity in the cortical motor areas after 0.9 Hz rTMS over the premotor cortex. Significance: Low-frequency rTMS changes the regional activation and functional coupling of cortical motor areas as demonstrated by EEG analysis. q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Premotor cortex; Motor cortex excitability; Repetitive transcranial magnetic stimulation; EEG power spectrum; Coherence; Functional reorganization 1. Introduction Repetitive transcranial magnetic stimulation (rTMS) can modulate the cortical excitability and provide an access to the study of cortical plasticity. The effect depends on several parameters including the rate and intensity of stimulation as well as the cortical region subjected to the stimulation (Wassermann, 1998). At stimulus intensities greater than the motor threshold (MT), high-frequency (. 5 Hz) rTMS increases cortical excitability (Pascual-Leone et al., 1994, 1998; Berardelli et al., 1998), whereas low-frequency (around 1 Hz) rTMS decreases it (Chen et al., 1997; Muellbacher et al., 2000; Maeda et al., 2000; Touge et al., 2001). So far, the majority of studies using low-frequency rTMS have focused on the excitability of the primary motor area and by using relatively high-intensity stimuli (90–115% of the resting MT) (Chen et al., 1997; Muellbacher et al., 2000; Maeda et al., 2000; Touge et al., 2001). The motor cortex excitability was often measured by TMS (Chen et al., 1997; Siebner et al., 1999; Muellbacher et al., 2000; Maeda et al., 2000; Touge et al., 2001), which applied artificial external stimulation and, therefore, might not reflect the physiological changes that occur during natural motor task. To overcome this point, several studies adopted the electroencephalogram (EEG) measurement Clinical Neurophysiology 114 (2003) 1628–1637 www.elsevier.com/locate/clinph 1388-2457/03/$30.00 q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S1388-2457(03)00063-4 * Corresponding author. Tel.: þ81-75-751-3601; fax: þ 81-75-751-3202. E-mail address: shib@kuhp.kyoto-u.ac.jp (H. Shibasaki).