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Brain Advance Access originally published online on October 13, 2004
Brain 2005 128(1):104-115; doi:10.1093/brain/awh315
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Brain Vol. 128 No. 1 © Guarantors of Brain 2004; all rights reserved

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

Nagako Murase1,4, John C. Rothwell5, Ryuji Kaji1, Ryo Urushihara1, Kazumi Nakamura1, Nobuki Murayama2, Tomohiko Igasaki2, Miyuki Sakata-Igasaki2, Tatuya Mima3, Akio Ikeda4 and Hiroshi Shibasaki4,6

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

Correspondence to: Ryuji Kaji, MD, PhD, Department of Neurology, Tokushima University School of Medicine, 5-1, Kuramoto-cho 2, Tokushima city 770-8503, Japan E-mail: rkaji{at}clin.med.tokushima-u.ac.jp

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.

6 Present address: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA


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