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Brain Advance Access published online on October 13, 2004

Brain, doi:10.1093/brain/awh315
© 2004 by Guarantors of Brain
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Received March 19, 2004
Revised June 29, 2004
Accepted September 2, 2004

Article

Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortex modulates writer's cramp

Nagako Murase 1, John C. Rothwell 2, Ryuji Kaji 3*, Ryo Urushihara 3, Kazumi Nakamura 3, Nobuki Murayama 4, Tomohiko Igasaki 4, Miyuki Sakata-Igasaki 4, Tatuya Mima 5, Akio Ikeda 3, and Hiroshi Shibasaki 6

1 Department of Neurology, Tokushima University School of Medicine, Tokushima, Japan; Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan
2 Sobell Department of Motor Neuroscience and Movement Disorders, MRC Human Movement and Balance Unit, Institute of Neurology, Queen Square, London, UK
3 Department of Neurology, Tokushima University School of Medicine, Tokushima, Japan
4 Department of Brain Research and Bioinformation, Graduate School of Science and Technology, Kumamoto University, Kumamoto, Japan
5 Human Brain Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
6 Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, Japan

* To whom correspondence should be addressed. E-mail: rkaji{at}clin.med.tokushima-u.ac.jp.


   Abstract

Summary Writer's cramp, or focal hand dystonia, is characterized by involuntary coactivation of antagonist or unnecessary muscles while writing or performing other tasks. Although the mechanism underlying this muscle overactivation is unknown, recent studies of changes in cerebral blood flow during writing have demonstrated a reduction in the activation of the primary motor cortex (MC) and hyperactivity of parts of the frontal non-primary motor areas. Therefore, any measures that decrease the activities of non-primary motor areas such as the premotor cortex (PMC) and the supplementary motor area (SMA) might improve dystonic symptoms. To explore this possibility, we studied nine patients with writer's cramp and seven age-matched control subjects, using subthreshold low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS), which exerts an inhibitory action on the cortex. Previous studies have demonstrated shortened cortical silent periods in dystonia, suggesting deficient cortical inhibition in the MC. We compared the silent periods and computer-assisted ratings of handwriting before and after rTMS applied to the MC, SMA or PMC. We also used the sham coil for control runs. Stimulation of the PMC but not the MC significantly improved the rating of handwriting (mean tracking error from the target, P = 0.004; pen pressure, P = 0.01) and prolonged the silent period (P = 0.02) in the patient group. rTMS over the other sites or using a sham coil in the patient group or trials in the control group revealed no physiological or clinical changes. This increased susceptibility of the PMC in dystonia suggests that the lack of inhibition in the MC is secondary to the hyperactivity of PMC neurons. Inhibition of the PMC using rTMS could provide a therapeutic measure of writer's cramp.

Keywords: dystonia; rTMS; premotor cortex; motor cortex; silent period.
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