Stimulation over the human supplementary motor area interferes with the organization of future elements in complex motor sequences

We used high-frequency repetitive transcranial magnetic stimulation (rTMS) to study the role of the mesial frontocentral cortex (including the supplementary motor area) in the organization of sequential finger movements of different complexity in humans. In 15 subjects, rTMS was randomly applied to the scalp overlying the region of the supplementary motor area and over other positions, including the contralateral primary motor cortex (hand area) during the performance of three overlearned finger sequences on an electronic piano. In all trials, rTMS (frequency 15-20 Hz) started 2 s after the first key press and lasted for approximately 2 s. All sequences were metronome-paced at 2 Hz and retrieved from memory. The 'simple' sequence consisted of 16 repeated index finger key presses, the 'scale' sequence of four times four sequential key presses of the little, ring, middle and index fingers, and the 'complex' sequence of a much less systematic and, therefore, more difficult series of 16 key presses. To measure the effects of rTMS interference with regional cortical function, we analysed rTMS-induced accuracy errors in the movement sequences. Stimulation over the supplementary motor area induced accuracy errors only in the complex sequence, while stimulation over the primary motor cortex induced errors in both the complex and scale sequences, and stimulation over other positions (e.g. F3, F4, FCz, P3, P4) did not interfere with sequence performance at all. Stimulation over the supplementary motor area interfered with the organization of subsequent elements in the complex sequence of movements, with error induction occurring approximately 1 s later than with stimulation over the primary motor cortex. Our findings are in keeping with recent results in non-human primates (Tanji J, Shima K. Nature, 1994; 371: 413-6) indicating a critical role of the supplementary motor area in the organization of forthcoming movements in complex motor sequences that are rehearsed from memory and fit into a precise timing plan.