Transcallosal inhibition in chronic subcortical stroke Julie Duque, a,b Friedhelm Hummel, a Pablo Celnik, a Nagako Murase, a,c Riccardo Mazzocchio, a,d and Leonardo G. Cohen a, * a Human Cortical Physiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20817, USA b Laboratory of Neurophysiology, University of Louvain, Brussels, Belgium c Department of Neurology, Tokushima University Faculty of Medicine, Tokushima, Japan d Sezione di Neurofisiologia Clinica, Dipartimento di Scienze Neurologiche e del Comportamento, Universita’ di Siena, Italy Received 28 January 2005; revised 24 June 2005; accepted 28 June 2005 Available online 9 August 2005 Movements of the paretic hand in patients with chronic subcortical stroke are associated with high interhemispheric inhibition (IHI) targeting the motor cortex in the lesioned hemisphere relative to healthy controls. The purpose of this investigation was to determine whether this abnormality also involves IHI operating during move- ments of the non-paretic hand. Here, we studied IHI in the process of generation of voluntary index finger movements by the paretic and non-paretic hands in a simple reaction time paradigm in a group of patients with chronic subcortical stroke. With movements of the non- paretic index finger, IHI targeting the contralateral primary motor cortex ( c M1) decreased progressively to turn into facilitation at around movement onset, similar to healthy controls. In contrast, movements of the paretic index finger resulted in significantly deeper inhibition at all premovement timings relative to the non-paretic hand. In conclusion, these results document a deeper premovement IHI with paretic than non-paretic hand movements of patients with chronic subcortical stroke, a possible mechanism underlying deficits in motor control. Published by Elsevier Inc. Keywords: Stroke; TMS; Interhemispheric inhibition; Rehabilitation; Motor control Introduction Activity in the intact hemisphere with movements of the paretic hand after chronic stroke is more prominent in patients with poor motor function (Cicinelli et al., 1997; Cramer et al., 1997; Netz et al., 1997; Traversa et al., 1998; Trompetto et al., 2000; Johansen- Berg et al., 2002; Calautti and Baron, 2003; Strens et al., 2003) and decreases over time with rehabilitation (Ward et al., 2003). The functional role of this activity is not clear. For example, the increased activation in the intact hemisphere of patients with stroke or hypoperfusion might reflect its direct contribution to motor performance or planning (Caramia et al., 2000; Krakauer et al., 2004; Luft et al., 2004). Alternatively, it is possible that this activity does not impact directly on motor function in the paretic hand (Werhahn et al., 2003) but reflects the increased influence of the intact hemisphere on homonymous regions of the lesioned hemisphere through transcallosal inhibitory interactions (Ferbert et al., 1992; Duque et al., 2005), as proposed by Murase et al. (2004). A previous study showed that, in healthy individuals, inter- hemispheric inhibition (IHI) targeting a primary motor cortex (M1) engaged in a motor task ( c M1, the motor cortex contralateral to the moving hand) is profound close to the Go signal in a simple reaction time paradigm. The magnitude of IHI progressively decreases to turn into facilitation at about movement onset (Murase et al., 2004). Modulation of IHI in the process of generation of a voluntary movement, one of the mechanisms proposed to support accurate motor performance (Geffen et al., 1994; Schnitzler et al., 1996; Murase et al., 2004), is disrupted when chronic subcortical stroke patients move the paretic hand, an abnormality that correlates with the magnitude of motor deficits (Murase et al., 2004). On the other hand, IHI associated with movements of the non- paretic hand of patients with chronic stroke has not been studied, an issue that could influence the balance of interhemispheric interactions and their impact on motor control in chronic stroke. Here, we studied movement-related modulation of IHI preceding 1053-8119/$ - see front matter. Published by Elsevier Inc. doi:10.1016/j.neuroimage.2005.06.033 Abbreviations: M1, primary motor cortex; c M1, primary motor cortex contralateral to the moving hand; i M1, primary motor cortex ipsilateral to the moving hand; IHI, interhemispheric inhibition tested with a TMS double-pulse paradigm; IHI c , IHI originating from i M1 and targeting c M1; IHI c rest , IHI c at rest; IHI c max , maximum IHI c recorded in the RT period preceding a voluntary movement; IHI c bef-mvt , IHI c immediately before movement; IHI c mvt-onset , IHI c around movement onset; CS, conditioning TMS pulse applied on i M1; TS, test TMS pulse applied on c M1; MEP(CS), MEPs evoked by CS; MEP(TS), MEPs evoked by TS in unconditioned trials (TS alone); MEP(CS + TS), MEPs evoked by TS in conditioned trials (CS + TS). * Corresponding author. Fax: +1 301 402 7010. E-mail address: cohenl@ninds.nih.gov (L.G. Cohen). Available online on ScienceDirect (www.sciencedirect.com). www.elsevier.com/locate/ynimg NeuroImage 28 (2005) 940 – 946