Modulation of motor cortical excitability following rapid-rate transcranial magnetic stimulation Eman M. Khedr a, * , John C. Rothwell b , Mohamed A. Ahmed a , Ola A. Shawky a , Mona Farouk c a Department of Neurology, Assiut University Hospital, Assiut, Egypt b Sobell Research Department of Motor Neuroscience and Movement Disorders (Dr. Rothwell), National Hospital for Neurology and Neurosurgery, London, UK c Department of Physiology Assiut University Hospital, Assiut, Egypt Accepted 11 September 2006 Available online 9 November 2006 Abstract Objective: To investigate the effect of high frequency rTMS (25 Hz at 90–100% of resting motor threshold) on the excitability of the motor cortex of healthy human subjects. Methods: Resting and active motor threshold, MEP recruitment curve (I/O curve), short interval intracortical inhibition (SICI) and facil- itation (ICF), and the duration of the silent period (SP) were tested in the right first dorsal interosseous muscle (FDI) before and twice after the end of 1500 pulses in 16 normal young adult male volunteers. Results: Twenty-five Hertz rTMS decreased motor thresholds, reduced the duration of the silent period and had a tendency to increase the slope of the I/O curve. Most of these effects lasted for the duration of the two post-testing sessions (at least 30 min) and had returned to normal by 2 h. There were no significant effects on SICI/ICF. Conclusion: Twenty-five Hertz rTMS can produce a long lasting increase in cortical excitability in healthy subjects. Significance: This method may prove useful for the study of normal human physiology and for therapeutic manipulation of brain plasticity. Ó 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Magnetic stimulation; Cortical excitability; Paired pulse stimulation 1. Introduction Repetitive transcranial magnetic stimulation (rTMS) is able of producing lasting changes in the excitability of neu- ronal networks, not only in the vicinity of the stimulating coil, but also at distant sites. The nature of the after effects, whether they are excitatory or inhibitory, and whether they affect just output neurones or interneurones, depends on the parameters of the rTMS. In general, high frequency (>5 Hz) stimulation is likely to yield excitation whereas lower frequencies or irregular patterns of stimulation can lead to inhibition (Pascual-Leone et al., 1994; Chen et al., 1997; Daskalakis et al., 2006; Gangitano et al., 2002; Huang and Rothwell, 2004; Maeda et al., 2000; Wu et al., 2000). The ability to control the excitability of cir- cuits in the brain for short periods has led to interest in try- ing to use the technique in a therapeutic manner in a variety of different diseases from depression to stroke. Because of concerns over the safety of rTMS, particular- ly the possibility of evoking seizures in non-epileptic sub- jects, most work has been carried out on patterns of stimulation that reduce excitability. However, as more experience is gained about the safety margins of the method, attention has begun to shift towards parameters of stimulation that can produce excitatory effects. In many cases, potential excitatory therapies have been tested on groups of patients before they have been tested on healthy subjects. The purpose of this paper is to begin to fill in some of these gaps in our knowledge. 1388-2457/$32.00 Ó 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2006.09.006 * Corresponding author. Fax: +20 2 088 2333327. E-mail address: emankhedr99@yahoo.com (E.M. Khedr). www.elsevier.com/locate/clinph Clinical Neurophysiology 118 (2007) 140–145