Neuroscience Letters 376 (2005) 188–193 Increased facilitation of the primary motor cortex following 1 Hz repetitive transcranial magnetic stimulation of the contralateral cerebellum in normal humans Massimiliano Oliveri a,b,∗ , Giacomo Koch a,c , Sara Torriero a , Carlo Caltagirone a,c a Laboratorio di Neurologia Clinica e Comportamentale, Unit` a di Neuropsicologia Sperimentale, Fondazione “Santa Lucia” IRCCS, Via Ardeatina, 306, 00179 Roma, Italy b Dipartimento di Psicologia, Universit` a di Palermo, Italy c Clinica Neurologica, Universit` a di Roma “Tor Vergata”, Italy Received 30 September 2004; received in revised form 27 October 2004; accepted 18 November 2004 Abstract Connections between the cerebellum and the contralateral motor cortex are dense and important, but their physiological significance is difficult to measure in humans. We have studied a group of 10 healthy subjects to test whether a modulation of the excitability of the left cerebellum can affect the excitability of the contralateral motor cortex. We used repetitive transcranial magnetic stimulation (rTMS) at 1Hz frequency to transiently depress the excitability of the left cerebellar cortex and paired-pulse TMS testing of intracortical inhibition (ICI) and intracortical facilitation (ICF) to probe the excitability of cortico-cortical connections in the right motor cortex. The cortical silent period was also measured before and after cerebellar rTMS. Motor evoked potentials (MEPs) were significantly larger after than before conditioning rTMS trains (p < 0.01). Moreover, left cerebellar rTMS increased the ICF of the right motor cortex as measured with paired-pulses separated by an interstimulus interval (ISI) of 15 ms. The effect lasted for up to 30 min afterward and was specific for the contralateral (right) motor cortex. The cortical silent period was unaffected by cerebellar rTMS. The implication is that rTMS of the cerebellar cortex can shape the flowing of inhibition from Purkinje cells toward deep nuclei, thereby increasing the excitability of interconnected brain areas. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: TMS; Cerebellum; Motor cortex; Motor evoked potentials There is wide anatomical evidence that cerebellar outputs project to a number of cortical areas, including the primary motor cortex (M1) [1,2,15] and dorsolateral prefrontal cortex [28]. From a physiological point of view, Purkinje cells of the cerebellar cortex project converging GABA-ergic inhibitory outputs to deep cerebellar nuclei, thus exerting a tonic mod- ulation on excitatory efferents from these structures to con- tralateral brain areas [21]. These data are supported by behavioral findings showing that the inhibitory activity of cerebellar cortical neurons is related to motor control and to cognitive aspects of motor per- formance [3]. The physiological coupling between cerebellar ∗ Corresponding author. Tel.: +39 065 1501584; fax: +39 065 1501388. E-mail address: maxoliveri@tiscali.it (M. Oliveri). and brain areas is now becoming the object of investigation also in humans by experimental techniques able to directly measure cortico-cortical coupling between distant sites [34]. One way to address this question is to examine the changes in cortical excitability induced in M1 by transient modula- tion of the excitability of the lateral cerebellum. rTMS is now the method of choice to modulate cortical excitability in conscious subjects. Trains with slow frequency (i.e. 1 Hz) are known to suppress cortical excitability [7,18,25,30], whereas facilitation occurs if frequencies higher than 5 Hz are used [4,5,14,29,32]. These changes in excitability occur not only at the site of stimulation but also at other distant intercon- nected sites of a network [12,17,31]. Previous studies showed that transcranial stimulation over the base of the skull reduces the excitability of contralateral 0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.11.053