Exp Brain Res (2009) 192:651–656 DOI 10.1007/s00221-008-1572-9 123 RESEARCH ARTICLE EVects of cerebellar TMS on motor cortex of patients with focal dystonia: a preliminary report F. Brighina · M. Romano · G. Giglia · V. Saia · A. Puma · F. Giglia · B. Fierro Received: 28 July 2008 / Accepted: 6 September 2008 / Published online: 25 September 2008  Springer-Verlag 2008 Abstract Recent evidence suggests a role for cerebellum in pathophysiology of dystonia. Here we explored, the cere- bellar modulation of motor cortex in patients with focal upper limb dystonia. Eight patients and eight controls underwent a transcranial magnetic stimulation protocol to study the cerebellar-brain-inhibition (CBI): a conditioning cerebellar stimulus (CCS) was followed 5 ms after by the contralateral motor cortex stimulation (test stimulus: TS). We explored the eVects of CBI on MEP amplitude, short intracortical inhibition (SICI) and intracortical facilitation (ICF) measures. At baseline no diVerences in TS-MEP amplitude, SICI or ICF were found between patients and controls. Cerebellar-conditioning signiWcantly reduced TS- MEP amplitude, increased ICF, and decreased SICI in con- trol subjects. In contrast, no changes in these neurophysio- logical measures were observed in the motor cortex of patients, regardless of which side was tested. If further con- Wrmed, these Wndings suggest a reduced cerebellar modula- tion of motor cortex excitability in patients with focal dystonia. Keywords TMS · Dystonia · Cerebellum · Motor cortex · Intracortical inhibition · Intracortical facilitation Introduction To date, the pathophysiology of dystonia remains largely unclear even if in some forms of focal dystonia (e.g. writer’s cramp) evidence of basal ganglia dysfunction has been provided (Mink 2003). Further studies have shown anomalies of sensory-motor circuits in writer’s cramp patients for which a reduced eYciency of motor intracorti- cal inhibition and a deWcit in sensory-motor integration was proposed (Quartarone et al. 2006; De Fazio et al. 2007). Recently, interest has grown in the role of the cerebellum in the pathophysiology of dystonia stimulated by cases of cer- ebellar structural abnormalities in dystonic patients (Delm- aire et al. 2007). These anomalies were particularly evident in a family of dystonic patients, where the basal ganglia were spared (Le Ber et al. 2006). Dystonia has been also described as a relevant clinical manifestation in some of the spinocerebellar ataxias, including forms in which patholog- ical lesions were restricted to the cerebellum (Manto 2005). Cerebellum involvement was previously provided by stud- ies showing functional abnormalities of both cerebellum and basal ganglia in primary dystonias (Eidelberger et al. 1998). Altered motor cortex (Quartarone et al. 2006; De Fazio et al. 2007) excitability has been described in dystonic patients and it is known that the cerebellum exerts a modu- latory inXuence on motor cortical areas. Ugawa et al. (1995) Wrst demonstrated that single pulse magnetic stimulation over the cerebellum aVects motor cor- tex excitability in normal subjects. The authors observed that a conditioning stimulus over the cerebellum suppresses EMG responses evoked by magnetic stimulation of the motor cortex when it preceded the cortical stimulus by 5– 7 ms. They considered the suppression mechanisms as resulting from a disfacilitation of the dentate-thalamo-cortical F. Brighina · G. Giglia · V. Saia · A. Puma · F. Giglia · B. Fierro (&) Department of Clinical Neurosciences, University of Palermo, Via G. La Loggia, 1, 90129 Palermo, Italy e-mail: Werro@unipa.it; fbrighina@unipa.it M. Romano Department of Neurology, Hospital “Villa SoWa”, Palermo, Italy