Orientation-specific, non NMDA-receptor dependent facilitation in the human motor cortex elicited by fast biphasic repetitive transcranial magnetic stimulation

Background and methods: To elucidate mechanisms of corticospinal facilitation outlasting 5Hz transcranial magnetic stimulation applied over the human primary motor cortex, we compared monophasic and biphasic pulses of anterior or posterior initial current direction in 8 healthy subjects. We tested six blocks of 200 pulses of each type at 90% active motor threshold and controlled for corticospinal excitability changes using motor evoked potential (MEP) amplitudes and latencies elicited by suprathreshold pulses before, in between and after rTMS.

Results: Only with biphasic pulses of initially anterior current direction did we find a gradual increase of MEP amplitudes during rTMS outlasting the stimulation by on average 5 minutes. Motor evoked potential latencies remained unchanged, and a control study on F-wave amplitudes excluded major changes in spinal excitability. In a pharmacological control study, both Carbamazepine and Lorazepam blocked the MEP facilitation after biphasic anteriorly oriented rTMS, whereas Dextrometorphan had no effect.

Conclusions: The data is consistent with a hypothesis that the initial quarter cycle of a biphasic pulse hyperpolarises the relevant interneurons, enhancing the depolarisation subsequently elicited by the second quarter cycle. We conclude that current direction and pulse waveform can be used to maximise effects outlasting fast rTMS. At subthreshold intensities, induction of facilitation obviously differs from induction of inhibition, since for the latter, earlier studies have shown a superiority of monophasic rTMS pulses.