Cerebellar and premotor function in bimanual coordination: parametric neural responses to spatiotemporal complexity and cycling frequency F. Debaere, a N. Wenderoth, a S. Sunaert, b P. Van Hecke, b and S.P. Swinnen a, * a Motor Control Laboratory, Department of Kinesiology, Group Biomedical Sciences, K.U. Leuven, Belgium b Magnetic Resonance Research Centre, Department of Radiology, Group Biomedical Sciences, K.U. Leuven, Belgium Received 14 July 2003; revised 6 December 2003; accepted 9 December 2003 In the present functional magnetic resonance imaging (fMRI) study, we assessed the neural network governing bimanual coordination during manipulations of spatiotemporal complexity and cycling frequency. A parametric analysis was applied to determine the effects of each of both factors as well as their interaction. Subjects performed four different cyclical movement tasks of increasing spatiotemporal complexity (i.e., unimanual left – right hand movements, bimanual in-phase movements, bimanual anti-phase movements, and bimanual 90j out-of-phase movements) across four frequency levels (0.9, 1.2, 1.5, and 1.8 Hz). Results showed that, within the network involved in bimanual coordination, functional subcircuits could be distinguished: Activation in the supplementary motor area, superior parietal cortex (SPS), and thalamic VPL Nc was mainly correlated with increasing spatiotempo- ral complexity of the limb movements, suggesting that these areas are involved in higher-order movement control. By contrast, activation within the primary motor cortex, cingulate motor cortex (CMC), globus pallidus, and thalamic VLo Nc correlated mainly with movement frequency, indicating that these areas play an important role during movement execution. Interestingly, the cerebellum and the dorsal premotor cortex were identified as the principal regions responding to manipulation of both parameters and exhibiting clear interaction effects. Therefore, it is concluded that both areas represent critical sites for the control of bimanual coordination. D 2004 Elsevier Inc. All rights reserved. Keywords: Bimanual coordination; fMRI; Parametric neural responses; Cerebellum; Premotor cortex; Relative phase; Movement complexity; Cycling frequency Introduction Coordination of both hands is required for many daily life activities (e.g., opening a bottle or tying shoelaces). Control of such coordination tasks is often disrupted in patients suffering from brain pathology (e.g., Brown et al., 1993; Serrien and Wiesendanger, 2000; Serrien et al., 2001; Stephan et al., 1999a,b; Swinnen, 2002). Therefore, investigation of the neural mechanisms governing coor- dination is of critical importance. Recently, imaging studies have provided valuable insights into the neural basis of bimanual coor- dination. These studies have generally revealed that bimanual coordination is associated with a widespread activation within a distributed sensorimotor network including the primary sensorimo- tor cortex (M1/S1), supplementary motor cortex (SMA), cingulate motor cortex (CMC), lateral premotor cortex (PMC), parietal cortex (PC), and subcortical structures, such as the basal ganglia and cerebellum (see Swinnen, 2002, for review). In particular, SMA, CMC, PMC, superior parietal cortex (SPC), and cerebellum are endowed with a more specific function in bimanual coordination, because higher or more pronounced activation has been found for these regions during coordinated movements as compared to single limb movements (Goerres et al., 1998; Jancke et al., 2000; Nair et al., 2003; Toyokura et al., 1999, 2001; Tracy et al., 2001), or during asymmetric and anti-phase coordination as compared to symmetric and in-phase coordination (Goerres et al., 1998; Immisch et al., 2001; Meyer-Lindenberg et al., 2002; Sadato et al., 1997; Stephan et al., 1999a,b; Toyokura et al., 1999; Ullen et al., 2003). Similar findings have been obtained during ipsilateral coordination of the hand and foot, indicating that the role of the abovementioned areas is not restricted to bimanual coordination but pertains to interlimb coordination in general (Debaere et al., 2001). The SMA and adjacent parts of CMC have most consistently been recognized as being important for rhythmical bimanual coordination (Goerres et al., 1998; Immisch et al., 2001; Jancke et al., 2000; Meyer-Lindenberg et al., 2002; Sadato et al., 1997; Stephan et al., 1999a,b; Toyokura et al., 1999, 2001; Ullen et al., 2003). By contrast, the specific contribution of other regions (PMC, SPC, cerebellum) seems to depend more on certain characteristics of the task requirements (Meyer-Lindenberg et al., 2002; Nair et al., 2003; Sadato et al., 1997; Tracy et al., 2001; Ullen et al., 2003). Apparently, activation in the latter areas increases when the coor- dination demands rise, which is either obtained by increased spatiotemporal complexity or higher execution frequency of the cyclical bimanual coordination tasks. This hypothesis, however, has never been tested directly. Behavioral studies have convincingly shown that the degree of difficulty of cyclical bimanual movements is determined mainly by 1053-8119/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2003.12.011 * Corresponding author. Laboratory of Motor Control, F.L.O.K. Group Biomedical Sciences K.U.L, Tervuurse Vest 101 3001, Heverlee, Belgium. Fax: +32-16-32-91-97. E-mail address: Stephan.Swinnen@FLOK.KULEUVEN.AC.BE (S.P. Swinnen). Available online on ScienceDirect (www.sciencedirect.com.) www.elsevier.com/locate/ynimg NeuroImage 21 (2004) 1416 – 1427