Effect of repetitive transcranial magnetic stimulation applied over the premotor cortex on somatosensory-evoked potentials and regional cerebral blood flow
Introduction
Somatosensory-evoked potentials (SEPs) have been used to explore the central mechanism of sensory input processing. SEP amplitudes are attenuated during voluntary (Papakostopoulos et al., 1975, Cohen and Starr, 1987) and passive (Brooke et al., 1996) movement or under mental simulation of movement (Cheron and Borenstein, 1992, Rossi et al., 2002). This attenuation is referred to as “gating”. SEPs are also gated before movement (Starr and Cohen, 1985, Shimazu et al., 1999, Asanuma et al., 2003), and clarification of its precise mechanism should help understand the sensorimotor integration in motor control of normal subjects and patients with basal ganglia disorders (Murase et al., 2000).
Transcranial magnetic stimulation (TMS) is a useful tool for studying the excitability and conductivity of the entire motor pathway from the cortex to the target muscle or the connectivity of the cerebral cortex. Recently, repetitive TMS (rTMS) has been used to apply a series of stimuli to a specific cortical area (Siebner and Rothwell, 2003, Murase et al., 2005). This can lead to long-lasting aftereffects on the excitability not only in the area itself, but also those areas that are functionally linked to it (Munchau et al., 2002). Because of its inhibitory effect on cortical excitability, low-frequency rTMS (<1 Hz) has been used for treating disorders related to brain hyperexcitability (Siebner et al., 1999, Hoffman and Cavus, 2002, Murase et al., 2005), whereas high-frequency rTMS (>5 Hz) exerts an excitatory influence on the cortex.
Non-primary motor areas may have an important role in sensorimotor integration for motor control because of their closer link to basal ganglia than the primary motor cortex. Although several studies have reported the effects of rTMS on SEPs (Enomoto et al., 2001, Tsuji and Rothwell, 2002, Satow et al., 2003, Ragert et al., 2004), only a few investigations have explored the effect of rTMS applied over non-primary motor areas (Siebner et al., 2003, Murase et al., 2005). In this study, using the clinically effective stimulation parameters in writer's cramp (Murase et al., 2005), we recorded SEPs immediately before and after application of monophasic very low-frequency (0.2 Hz) rTMS over the primary and non-primary motor cortices of normal subjects to investigate the role of these areas on processing sensory input. In rTMS over PMC, we also recorded SEPs immediately before and after biphasic low-frequency (1 Hz) rTMS to investigate the frequency or phase specificity of the rTMS aftereffects on median SEPs. In addition, we recorded single photon emission computed tomography (SPECT) and compared regional cerebral blood flow (rCBF) images immediately before and after monophasic 0.2 Hz rTMS over PMC to investigate changes in cortical blood flow associated with those in SEPs.
Section snippets
Subjects
Nine healthy right-handed subjects (all men aged 30.2 ± 8.8 years) participated in this study. All subjects gave their informed consent for the study, which was approved by the Ethics Committee of the University of Tokushima, School of Medicine. The subjects were free from neurological and psychiatric diseases.
Experimental design
SEPs were recorded immediately before and after application of monophasic rTMS; 250 pulse trains were delivered at 0.2 Hz over the right-hand motor area (MC), the premotor area (PMC), or
SEPs
Fig. 2 shows the grand-averaged waveforms from 9 subjects. Because of the variations of latencies across the subjects, grand-averaged waveforms were constructed by adjusting the time to coincide the P14 peaks of each average. At both electrodes, the subcortical far-field P14 component was the first activity detected in all subjects. Table 1 shows the peak latencies and amplitudes of each component and their differences before and after application of monophasic 0.2 Hz rTMS over three cortical
Discussion
In the present study, we compared median SEPs before and after application of monophasic very low-frequency subthreshold rTMS over the primary and non-primary motor cortices. Application of monophasic 0.2 Hz rTMS over PMC, but not over MC or SMA, significantly increased the amplitude of frontal N30 component, but not of the parietal counterpart, and this effect was not seen after biphasic 1 Hz rTMS over PMC. This change was associated with increased rCBF in PMC and prefrontal cortex, as
Acknowledgments
We thank T. Mima for helpful suggestions and R. Ushijima for technical support. R.U. was supported by a Grant-in-Aid for the 21st Century COE Program, Human Nutritional Science on Stress Control, Tokushima, Japan.
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