The temporal characteristics of motion processing in hMT/V5+: Combining fMRI and neuronavigated TMS Alexander T. Sack, a, * ,1 Axel Kohler, b,c,1 David E.J. Linden, b,d,e Rainer Goebel, a and Lars Muckli b,c a Department of Neurocognition, Faculty of Psychology, Maastricht University, PO Box 616, Postbus 616, 6200 MD Maastricht, The Netherlands b Department of Neurophysiology, Max Planck Institute for Brain Research, Deutschordenstr. 46, 60528 Frankfurt am Main, Germany c Brain Imaging Center Frankfurt, Schleusenweg 2 – 6, 60590 Frankfurt am Main, Germany d School of Psychology, University of Wales, Bangor, UK e Department of Psychiatry, Johann Wolfgang Goethe University, Heinrich-Hoffmann-Str. 10, 60528 Frankfurt am Main, Germany Received 22 February 2005; revised 15 August 2005; accepted 23 August 2005 Available online 26 September 2005 Functional imaging has demonstrated the specific involvement of the human middle – temporal complex (hMT/V5+) during processing of moving stimuli. Some studies applied transcranial magnetic stimulation (TMS) to investigate the causal relevance of hMT/V5+ for motion perception. Although the studies used similar visual stimuli and TMS parameters, the critical time point of functionally relevant hMT/V5+ activity differed by 100 ms and more. The present study aimed to elucidate further the temporal characteristics of motion processing in hMT/V5+ by investigating all critical time windows currently debated in the literature. In contrast to previous studies, we used TMS neuronavigation based on individual fMRI results of five participants to target hMT/V5+, applying single- pulse TMS at 24 different time windows (À50 till +200 ms relative to stimulus onset). We revealed that TMS significantly impaired motion perception when applied over hMT/V5+ at 40 to 30 ms before as well as 130 to 150 ms after onset of the moving stimuli. While the late effective time window conforms to results from previous experiments, we did not find evidence for an early time window around 0 ms that has been reported in other studies. Our neuronavigation approach enabled us to quantify the inter- individual variance in the exact location of hMT/V5+ and the respective TMS target position on the skull of the participants. Considering that shifting the TMS coil position only by a few millimeters can already lead to a complete loss of TMS effects, our study clearly demonstrates the utility of neuronavigated TMS when investigating specific neuronal effects as in the case of motion processing. D 2005 Elsevier Inc. All rights reserved. Introduction The perception of motion represents one of the most crucial abilities of our visual system, enabling us to survive in a dynamically changing environment. A large number of electrophysiological (Albright et al., 1984; Cook and Maunsell, 2002; Diogo et al., 2003; Snowden et al., 1991; Van Essen et al., 1981; Zeki, 1974) and functional imaging studies (Gulyas et al., 1994; Heeger et al., 1999; Huk et al., 2002; Rees et al., 2000; Seiffert et al., 2003; Tootell et al., 1995b; Watson et al., 1993; Zeki et al., 1991; see Orban et al., 2004 for a review) have shown that within the network of specialized regions in the visual system, the extrastriate visual area hMT/V5+, located in the occipitotemporal cortex, is specifically activated during the processing of moving stimuli. Although likely, this evidence alone does not allow inferences on the causal role of neuronal activity in hMT/V5+ for motion perception. A causal relationship can only be inferred if a documented change of activity in hMT/V5+ causes a related change in motion perception. Neuronal activity in hMT/V5+ can be disrupted due to lesions or it can be manipulated experimentally by transcranial magnetic stimulation (TMS) in humans (Sack and Linden, 2003) or cooling in animals (Hupe ´ et al., 2001). Several lesion (Baker et al., 1991; Newsome and Pare ´, 1988; Vaina and Cowey, 1996; Zihl et al., 1983) and TMS studies (Anand et al., 1998; Beckers and Ho ¨ mberg, 1992; Beckers and Zeki, 1995; d’Alfonso et al., 2002; Hotson et al., 1994; Hotson and Anand, 1999; Walsh et al., 1998) have confirmed a causal relation between hMT/V5+ activity and performance on visual motion tasks. The demonstration that TMS over hMT/V5+ can also disrupt the storage and perception of the so-called motion after-effect (The ´oret et al., 2002; see also Antal et al., 2004b) and even produce moving phosphenes (Antal et al., 2003, 2004a; Campana et al., 2002; Stewart et al., 1999) complements the evidence that this area is functionally relevant for the processing of moving stimuli. 1053-8119/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2005.08.027 * Corresponding author. Fax: +31 43 3884125. E-mail address: a.sack@psychology.unimaas.nl (A.T. Sack) 1 These authors contributed equally to this work. Available online on ScienceDirect (www.sciencedirect.com). www.elsevier.com/locate/ynimg NeuroImage 29 (2006) 1326 – 1335