Elsevier

NeuroImage

Volume 31, Issue 2, June 2006, Pages 699-709
NeuroImage

Effect of repetitive transcranial magnetic stimulation applied over the premotor cortex on somatosensory-evoked potentials and regional cerebral blood flow

https://doi.org/10.1016/j.neuroimage.2005.12.027Get rights and content

Abstract

Somatosensory-evoked potentials (SEPs) are attenuated by movement. This phenomenon of ‘gating’ reflects sensorimotor integration for motor control. The frontal N30 component after median nerve stimulation was shown to be reduced in amplitude prior to hand movement. To investigate the mechanism of this sensory gating, we recorded median SEPs immediately before and after application of monophasic very low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS) of 250 stimuli over motor cortex (MC), premotor cortex (PMC), or supplementary motor area (SMA) in 9 healthy volunteers. The stimulus intensity for MC or PMC was set 85% of the resting motor threshold for the hand muscle, and that for SMA was at the active motor threshold for the leg muscle. SEPs showed significant increases in amplitudes of the frontal N30 component after PMC stimulation, but not after SMA or MC stimulation. Low-frequency (1 Hz) biphasic stimulation over PMC showed no significant N30 changes in 6 out of 9 subjects tested, indicating the effect being specific for 0.2 Hz monophasic stimulation. To examine the functional anatomy of the N30 change, single photon emission computed tomography was performed immediately before and after monophasic 0.2 Hz rTMS over PMC in all the 9 subjects. Regional cerebral blood flow showed significant increases mainly in PMC and prefrontal cortex, indicating the involvement of these cortical areas in sensory input gating for motor control.

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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