From will to action: sequential cerebellar contributions to voluntary movement Ernst Hu ¨lsmann,* Michael Erb, and Wolfgang Grodd Section on Experimental Magnetic Resonance of CNS, Department of Neuroradiology, University of Tu ¨bingen, Hoppe-Seyler-Strape 3, 72076 Tu ¨bingen, Germany Received 23 December 2002; revised 4 April 2003; accepted 12 May 2003 Abstract The cerebellum is known to be involved in numerous motor related functions, but recent observations suggest that it also performs fundamental operations on nonmotor functions such as perception and cognition. Assuming that the cerebellum has to be consulted in a limited window of time, cerebellar activation should occur in a time-dependent manner in respect to the corresponding telencephalic areas. This hypothesis was tested by combining a simple motor task with the demand of a self-paced delay using event-related functional magnetic resonance imaging. Evaluation with a time-shifted canonical hemodynamic response function revealed spatially and temporally separated cerebral and cerebellar activation accompanying the entire process—from conscious planning to final motor output—within a time frame of 6 s. The cerebral activations spread from the anterior cingulate cortex through the supplementary motor and premotor area to the primary motor and sensory cortices. This cascade was temporally in parallel with cerebellar activations propagating from the neo- to the spinocerebellum. An early lateral cerebellar recruitment 3 s prior movement onset confirms its involvement in cognitive processing. A later medial activation occurring close to movement onset most probably reflects spinocerebellar kinesthetic feedback. Between these two points a striking lateromedial succession was found, which is in line with the hypothesis of the existence of multiple internal models residing in the cerebellum, each communicating with its own corresponding telencephalic region. © 2003 Elsevier Inc. All rights reserved. Keywords: Functional magnetic resonance imaging (fMRI); Voluntary movement; Cerebellum; Motor system; Hemodynamic response function; Temporal dynamics Introduction The spatial, temporal, and hierarchical properties of the central nervous system that serve consciously controlled human output have been studied extensively over the past decades. This network, incorporating voluntary, intended human actions, is quite well understood at the telencephalic cortical level. For example, a visual signal arrives at the visual cortex (VI) and spreads via the visual stream to the prefrontal cortex (PFC). Here it is held in the working memory, embedded in the context of other sensations, and can be manipulated by an executive controller (Baddley, 1992). Areas located on the medial wall of the cerebral hemispheres are recruited when the brain reacts to the signal with a self-controlled action. Movement planning and prep- aration occurs in secondary motor areas—the anterior cin- gulate cortex (ACC) (Paus, 2001), the supplementary motor cortex (SMA), the premotor area (PM), and, in particular, the preSMA (Thickbroom, 2000). The program generated here reaches downstream the primary motor cortex (M1) to release the movement. Sensory feedback of this movement will, finally, reach the primary sensor cortex (S1). The different delays in the cascade’s evolution can range from years (between a signal and its consecutive answer) to seconds (between M1 and S1). The underlying neurophys- iological processes of anticipatory behavior and motor plan-  Supplementary data associated with this article can be found at doi: 10.1016/S1053-8119(03)00307-0. * Corresponding author. Ernst Hu ¨lsmann Section on Experimental Magnetic Resonance of CNS, Department of Neuroradiology, University of Tu ¨bingen. Fax: +49-7071-29-4371. E-mail address: ErnestHuelsmann@aol.com (E. Hu ¨lsmann). NeuroImage 20 (2003) 1485–1492 www.elsevier.com/locate/ynimg 1053-8119/$ – see front matter © 2003 Elsevier Inc. All rights reserved. doi:10.1016/S1053-8119(03)00307-0