Recovery of skilled reaching following motor cortex stroke: do residual corticofugal fibers mediate compensatory recovery? Omar A. Gharbawie, Jenni M. Karl and Ian Q. Whishaw Department of Neuroscience, Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, AB, T1K 3M4, Canada Keywords: caudal motor cortex, corticospinal fibers, rat, rostral motor cortex Abstract Motor cortex (MC) injury impairs skilled reaching in rats, but success scores are eventually restored to approximate preoperative levels. The improvement is attributed to compensatory strategies, such as substituting trunk rotations for the chronically lost rotatory movement of the forelimb, that occur during transport and withdrawal. The present study examined the contributions of the rostral motor cortex (RMC) and the caudal motor cortex (CMC) to skilled reaching performance. The study also examined the role of the ipsilateral and the contralateral hemispheres in supporting the spontaneous recovery. Rats were trained to reach for single food pellets, and their recovery from partial or complete MC injury was documented with quantitative scores and movement element measures in three experiments: (1) devascularization of the CMC, or the RMC, or both, in the hemisphere contralateral to the reaching paw; (2) additional lesions to the CMC and RMC injuries such that the conjoint damage amounted to an MC lesion; and (3) MC lesion followed by damage in the neocortex lateral to the injury or in the opposite MC. The results showed that the CMC made the main contribution to skilled reaching performance, and that there was a lesser contribution by the RMC. MC damage was exacerbated by additional damage to the ipsilateral neocortex as compared to the contralateral neocortex. The results are discussed in relation to the idea that the involvement of the neocortical areas in skilled reaching performance and its recovery is proportional to the region from which corticospinal projections originate. Introduction Rats are adept at reaching for, grasping and bringing food to the mouth with a single paw, a behavior termed skilled reaching (Whishaw & Pellis, 1990; Whishaw, 2005). The motor cortex (MC) and its fiber projections contribute to the skill, and are especially involved in the rotatory movements of the forelimb. The demand that skilled reaching places on the MC is reflected in forelimb motor map reorganization. Intracortical microstimulation (ICMS) shows an expansion of distal forelimb movement representations (wrist and digits) at the expense of proximal forelimb movement representations (shoulder and elbow) within the MC in response to reach training but not strength training or repetitive bar pressing (Nudo et al., 1996a; Remple et al., 2001; Kleim et al., 2004). The reorganization is supported by enhancements in synaptic efficacy (Rioult-Pedotti et al., 1998; Monfils & Teskey, 2004), synaptogenesis (Kleim et al., 2002, 2004) and protein synthesis (Kleim et al., 2003; Luft et al., 2004) within the MC. The importance of the MC to skilled reaching is also reflected in the reaching impairments that ensue after MC injury (Castro, 1972a; Whishaw et al., 1986, 1991; Miklyaeva et al., 1993; Gonzalez & Kolb, 2003; Emerick & Kartje, 2004; Metz et al., 2005) or pyramidal tract section (Castro, 1972b; Whishaw et al., 1993; Z’Graggen et al., 1998; Piecharka et al., 2005). Nevertheless, rats eventually recover the ability to reach for and grasp food after injury, as shown by near complete restoration of success scores within 2–3 weeks of injury (Whishaw, 2000). The reaching movement is not normal, however, because trunk rotation compensates for rotatory movements once performed by the forelimb (Whishaw et al., 1991; Whishaw, 2000; Metz et al., 2005). To varying extents, recovery from MC or corticospinal injury has been reported in human and nonhuman primates as well. There are several explanations for the neural basis of this recovery. One view is that the recovery of hand dexterity is supported by functional reorganization within peri-infarct tissue (Glees & Cole, 1950; Nudo et al., 1996a; Liu & Rouiller, 1999; Frost et al., 2003; Werhahn et al., 2003; Fridman et al., 2004; Jaillard et al., 2005). The pertinence of this reorganization for recovery may be appreciated from the reinstatement of hand use deficits after temporary deactivation (Liu & Rouiller, 1999; Werhahn et al., 2003; Fridman et al., 2004) or permanent lesion (Glees & Cole, 1950) of perinfarct tissue but not homotopic regions in the opposite hemisphere. A second view suggests that modest recovery is supported by functional reorganiza- tion in the contralateral-to-lesion hemisphere, whereas more favorable recovery outcomes are supported by reorganization within the ipsilateral-to-lesion hemisphere. Longitudinal functional magnetic resonance imaging supports this view by showing increased activation in the contralateral-to-lesion hemisphere in the immediate period after stroke when impairments are most severe, but increased activation shifts to peri-infarct regions as function improves (Marshall et al., Correspondence: Dr O. A. Gharbawie, as above. E-mail: omar.gharbawie@vanderbilt.edu Received 25 February 2007, revised 13 August 2007, accepted 5 September 2007 European Journal of Neuroscience, Vol. 26, pp. 3309–3327, 2007 doi:10.1111/j.1460-9568.2007.05874.x ª The Authors (2007). Journal Compilation ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd