Handedness is mainly associated with an asymmetry of corticospinal excitability and not of transcallosal inhibition Luigi De Gennaro a, * , Riccardo Cristiani a , Mario Bertini a , Giuseppe Curcio a , Michele Ferrara a,b , Fabiana Fratello a , Vincenzo Romei a , Paolo M. Rossini c,d,e a Dipartimento di Psicologia, Universita ` di Roma, ‘La Sapienza’, Via dei Marsi, 78, 00185 Rome, Italy b Dipartimento di Medicina Interna e Sanita ` Pubblica, Universita ` di L’Aquila, L’Aquila, Italy c Clinica Neurologica, Universita ` di Roma ‘Campus Bio-medico’, Rome, Italy d AFaR, Dip. Neuroscienze Osp. Fatebenefratelli, Isola Tiberina, Rome, Italy e IRCCS, ‘Centro S.Giovanni di Dio-Fatebenefratelli’, Brescia, Italy Accepted 25 January 2004 Abstract Objective: The study aims to compare transcallosal inhibition (TI), as assessed by the paired-pulse transcranial magnetic stimulation (TMS) technique, in a sample of right-handed subjects (RH) and left-handed subjects (LH). Motor thresholds (MTs) and motor evoked potential (MEP) amplitudes were also measured in the two groups, as an index of corticospinal activity. Methods: Thirty-two normal subjects (16 RH and 16 LH) were recorded with a paired-pulse TMS paradigm (intensity of both pulses ¼ 120% of MT). The inter-stimulus intervals (ISIs) were 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20 ms for both motor cortices, and MEP responses were recorded from the abductor digiti minimi muscles. Results: Both groups showed a clear TI centred around the 12 ms ISI, but no difference was found as a function of handedness or of hemisphere. On the other hand, the two groups differed in terms of corticospinal activity, since the hand motor dominant hemisphere had lower MTs than the non-dominant one in LH, and larger MEP amplitudes for the right hand were found in RH. Conclusions: Results point to a functional asymmetry of the motor cortex on the hand-dominant versus the non-dominant hemisphere, while handedness does not seem associated with functional differences in callosal inhibition, as measured by the inter-hemispheric paired- pulse TMS technique. q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Transcranial magnetic stimulation; Handedness; Paired-pulse technique; Transcallosal inhibition; Corpus callosum; Corticospinal system; Gender 1. Introduction Several studies in recent years have assessed the association between handedness and inter-hemispheric connectivity. Volumetric measurements found a larger corpus callosum (CC) in left-handers compared to right- handers (Clarke and Zaidel, 1994; Cowell et al., 1993; Denenberg et al., 1991; Habib et al., 1991; Luders et al., 2003; Moffat et al., 1998; Preuss et al., 2002). The size of the CC has been related to the number of myelinated and non-myelinated fibres involved in the transmission of neuronal activity (Aboitiz et al., 1992), to functional cortical activation assessed by fMRI during uni- and bi- manual movements (Stancak et al., 2003), and to hemi- spheric speech representation (Moffat et al., 1998). Considering the uncertainty of dividing the CC into subregions (e.g. Peters et al., 2002), the existence of CC connections between the homotopic and heterotopic cortical regions (e.g. Seltzer and Pandya, 1983), the sparse callosal fibres connecting M1 areas (Rouiller et al., 1994), and the lack of a direct physiological measure of CC activity in humans, it is not surprising that the relationship between CC morphology and motor activity in handedness groups has not been established once and for all. A measure of CC activity in humans is now provided by a recent transcranial magnetic stimulation (TMS) paradigm using inter-hemispheric paired pulses. TMS is now an 1388-2457/$30.00 q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2004.01.014 Clinical Neurophysiology 115 (2004) 1305–1312 www.elsevier.com/locate/clinph * Corresponding author. Tel.: þ 39-6-4991-7647; fax: þ39-6-4451-667. E-mail address: luigi.degennaro@uniroma1.it (L. De Gennaro).