O1: Effects of quadripulse stimulation over medial frontal cortex on human visuomotor sequence learning

Introduction Motor learning is important to perform skillful movements automatically in daily life. The medial frontal cortices, cerebellum and basal ganglia are activated in the motor learning processes. Especially, the pre-supplementary motor area (pre-SMA) is considered to play important roles in learning new visuomotor sequence movements. A functional MRI study revealed that pre-SMA was activated during learning of a new sequence with button press tasks ( Hikosaka et al., 1996 ). To learn new motor sequence, neural plastic change should occur in the pre-SMA. Non-invasive brain stimulation (NIBS) such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) can induce plasticity-like effects on human brain structures. The motor learning performances could be modulated by stimulation over some relevant area for this process. The medial frontal cortices have not been a main target of motor learning process studies. Objectives To study whether plastic changes in the medial frontal cortices can modulate human visuomotor sequence learning using quadripulse stimulation (QPS), a new patterned rTMS technique. Materials and methods Seven healthy volunteers participated. We applied QPS or sham stimulation over left pre-SMA for 30 min. QPS consisted of repeated trains of four monophasic TMS pulses separated by inter-stimulus intervals of 5 ms (QPS-5) or 50 ms (QPS-50) with an inter-train interval of 5 s. QPS-5 was reported to induce LTP in stimulated cortex, and QPS-50 Ltd. After QPS, each subject performed the 2 × 10 task, which is similar to the visuomotor sequential task reported by Hikosaka et al. Participants asked to press 2 illuminated buttons from 16 buttons in the correct order which he must learn by trial-and-error. A total of 10 pairs were presented in a fixed order for completion. As a behavioural outcome, we counted the number of errors to complete 20 successful trials to assess the performance accuracy, and measured movement time (MT): the time from the first button release to the second button press, and the button press reaction time (BP-RT): the time from stimulus onset to the first button press to assess the performance speed. Results The number of errors was larger in QPS-5 compared to sham stimulation, whereas it did not differ between QPS-50 and sham conditions. Neither MT nor BP-RT differed significantly among any stimulation conditions. Conclusion QPS-5 over pre-SMA reduced the motor learning performances. Several possible mechanisms can explain this finding: QPS5 may induce LTP of inhibitory neurons, BCM curve may shift from the curve of M1 in pre-SMA, metaplasticity may occur after QPS, inverse BCM for pre-SMA or others.