Evaluation of the effective connectivity of supplementary motor areas during motor imagery using Granger causality mapping Huafu Chen a, ⁎, Qin Yang a , Wei Liao a , Qiyong Gong b,c , Shan Shen a,d a Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, PR China b Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, 610041, PR China c The Division of Medical Imaging, Faculty of Medicine, University of Liverpool, UK d Clinical Neuroscience Research Team, Department of Psychology, University of Surrey Guildford GU2 7XH, UK abstract article info Article history: Received 18 January 2009 Revised 22 April 2009 Accepted 11 June 2009 Available online 18 June 2009 Keywords: Effective connectivity Feedback Granger causality Motor imagery Supplementary motor areas Brain activation during motor imagery has been studied extensively for years, but only a few of these studies focused on investigating the effective connectivity in the brain. The existence of interactions or closed loop circuits between the SMA and other brain regions during motor imagery still remains unclear. In the present study, selecting the SMA as the region of interest, we used the Granger causality mapping (GCM) method to explore the effective connectivity in the brain during motor imagery. Our results demonstrated that more brain regions showed effective connections to the SMA during the right-hand motor imagery than during the left-hand motor imagery, but the strength of the casual influence during the left-hand motor imagery was stronger than that of the right-hand motor imagery. We further found forward and backward effective connectivity between the SMA and three regions, including the bilateral dorsal premotor area (PMd), the contralateral primary and secondary somatosensory cortex (S1), and the primary motor cortex (M1). these results might indicate how the brain regions were inter-activated during motor imagery. © 2009 Elsevier Inc. All rights reserved. Introduction Motor imagery, defined as the mental rehearsal of motor move- ment without any overt body movement (Jeannerod 1995; Porro et al., 1996), has been demonstrated to play a very important role in training for athletes and musicians (Lotze and Halsband, 2006), and also in the recovery of motor abilities in patients with movement disorders (Malouin et al., 2004; Kimberley et al., 2006). In particular, motor imagery was often performed using two different strategies, visual imagery (Solodkin et al., 2004), i.e. people produce a visual representation of their movements, and kinetic imagery, i.e. people simulate the movement with a kinesthetic feeling. Benefited from brain imaging techniques, such as functional magnetic resonance imaging (fMRI) and positron emission tomogra- phy (PET), motor imagery has been studied intensively for years. Among the activated brain areas during motor imagery, the supple- mentary motor area (SMA) was reported to be the most active area and plays an important role in motor imagery tasks as well as in the high-level motor control (Gerardin et al., 2000; Nair et al., 2003; Lacourse et al., 2005; Michelon et al., 2006; Szameitat et al., 2007). It was also found to be involved in the programming of movements (Cunnington et al., 1996). Recently, the interactions between the SMA and some specific regions during motor imagery were investigated, in which effective connectivity (Friston et al., 1993) among brain regions was calculated. Solodkin et al. (2004) used structural equation modeling to estimate the networks underlying motor execution and motor imagery with specified regions of interest. A more recent study (Kasess et al., 2008) analyzed the interaction between the SMA and the primary motor cortex (M1) by dynamic causal modeling (DCM) (Friston et al., 2003) and showed that the SMA exerted a suppressive influence on the M1 during motor imagery. Besides the SMA, there are several other brain regions, such as the dorsal premotor area (PMd) and inferior parietal lobule (IPL), also participating in motor imagery as addressed by many studies (Lortze et al., 1999; Simon et al., 2002; Hanakawa et al.,, 2003; Nair et al., 2003; Solodkin et al., 2004; Lacourse et al., 2005; Lotze and Halsband, 2006; Szameitat et al., 2007). Aiming to obtain a clear picture on the interaction networks between the SMA and all these important regions involved in motor imagery, we employed the Granger causality mapping (GCM) method (Goebel et al., 2003; Roebroeck et al., 2005; Deshpande et al., 2008; Gao et al., 2008) to investigate this inter-regional interaction. GCM is an important approach to explore Granger causal relationships between two time series. It can detect the effective connectivity in the brain by its predictive power based on the assumption that the hemodynamic response function (HRF) is capable of measuring inter-regional latencies (chronometry) (For- misano and Goebel, 2003; Hulsmann et al., 2003; Menon et al., 1998; Mohamed et al., 2003). NeuroImage 47 (2009) 1844–1853 ⁎ Corresponding author. Fax: +86 28 83208238. E-mail address: Chenhf@uestc.edu.cn (H. Chen). 1053-8119/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2009.06.026 Contents lists available at ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/ynimg