Acute Effect of Subthreshold Low-frequency Repetitive Transcranial Magnetic Stimulation over the Premotor Cortex in Writer´s Cramp

Writer´s cramp, or focal hand dystonia, is characterized by involuntary coactivation of antagonist or unnecessary muscles while writing or performing other tasks. 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 the parts of frontal nonprimary motor areas. Therefore, any measures that decrease the activities of nonprimary motor areas like the premotor cortex (PMC) or supplementary motor area (SMA) might improve dystonic symptoms. We explore this possibility of acute effect, Nine patients with writer´s cramp and seven age-matched control subjects were recruited. After the preliminary experiments, we used subthreshold low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS), which exerts an inhibitory action on the cortex. We compared the silent periods and computer-assisted ratings of handwriting before and after rTMS applied to the MC, SMA, or PMC. 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. This increased susceptibility of the PMC in dystonia suggests that lack of inhibition in the MC is secondary to the hyperactivity of PMC neurons. Further physiological studies disclosed that the amplitude of frontal N30 component was significantly increased after rTMS over the PMC in control subjects (p=0.014) but not in dystonic patients, and 99mTc-ECD SPECT showed the different activation pattern in between control subjects (Brodmann area 9 and 6 including PMC and prefrontal cortex) and patients (parietal and cerebellar cortices). These findings support the idea that cortical network pattern induced by rTMS is quite different in the two groups. It is not clear whether the activated areas seen in dystonia is due to primary or compensatory mechanism, but our findings sugge- st the PMC plays an important role in the pathophysiology of dystonia. Additionally we showed 0.2 Hz rTMS over the premotor cortex was rather effective than ordinary 1 Hz stimulation over the MC, demonstrating that different frequency and stimulation site is to be explored in each disease depending on its own pathophysiology.