Long-lasting inhibition of cerebellar output

Abstract

The cerebellar influence on the motor cortex output is exerted mostly though the cerebellothalamocortical pathway (CTC). One way to explore this pathway is by the means of transcranial magnetic stimulation (TMS). A single-pulse conditioning magnetic stimulation delivered over the lateral cerebellum was shown to diminish the excitability of the contralateral motor cortex 5 milliseconds later (cerebellocortical inhibition [CBI]), most likely through transynaptic activation of cerebellar Purkinje cells, which in turn inhibit the tonic activity of the CTC. Repetitive TMS (rTMS) delivered over the lateral cerebellum was shown to induce a long-lasting change of the cortical excitability, as well, but the mechanism and time course of this effect are still debated. We tested the time course of the effects of rTMS on the CBI in five paradigms: (1) 1 Hz rTMS, (2) continuous theta burst stimulation (cTBS), and (3) intermittent TBS (iTBS) over the right cerebellum, (4) 1 Hz rTMS over the cervical nerve roots, and (5) 1 Hz rTMS over the left cerebellum. Surface electromyography was recorded from the right first dorsal interosseous (FDI) and adductor digiti minimi. A double-cone coil was used for single-pulse cerebellar stimulation, whereas a figure-of-eight coil was used for the rTMS. The stimulus intensity was set at 90% of the M1 resting motor threshold for 1 Hz rTMS, and at 80% of the M1 active motor threshold for TBS. Both types of cerebellar stimulation were performed under magnetic resonance image (MRI)-guided neuronavigation centered over the right VIII B lobule, and stimulation intensities were adjusted for cerebellar cortex depth. A figure-of-eight coil was used for left motor cortex stimulation. There was significant CBI suppression to the left motor cortex up to 30 minutes after the 900 stimuli of 1 Hz rTMS over either cerebellar hemisphere, and after 600 stimuli of cTBS over the right cerebellum, but not after 600 stimuli of iTBS over the right cerebellum, or after 900 of 1 Hz rTMS stimuli delivered over the cervical nerve roots. The 1 Hz rTMS over the left cerebellum significantly reduced the CBI in the right FDI 10 minutes after the end of the intervention. The amplitudes of the unconditioned cortical motor-evoked potentials were not significantly changed. Our findings suggest that repetitive cerebellar stimulation operate at a cerebellar level, rather then at a cortical level.