AUTHOR COPY NeuroRehabilitation 33 (2013) 13–24 DOI:10.3233/NRE-130923 IOS Press 13 Targeted engagement of a dorsal premotor circuit in the treatment of post-stroke paresis Lucy Dodakian a , Kelli G. Sharp a , Jill See a , Neil S. Abidi a , Khoa Mai a , Brett W. Fling a , Vu H. Le a and Steven C. Cramer a,b,∗ a Department of Anatomy & Neurobiology, University of California, Irvine, CA, USA b Department of Neurology, University of California, Irvine, CA, USA Abstract. BACKGROUND: Good motor outcome after stroke has been found to correlate with increased activity in a dorsal premotor (PMd) brain circuit, suggesting that therapeutic strategies targeting this circuit might have a favorable, causal influence on motor status. OBJECTIVE: This study addressed the hypothesis that a Premotor Therapy that exercises normal PMd functions would provide greater behavioral gains than would standard Motor Therapy; and that Premotor Therapy benefits would be greatest in patients with greater preservation of PMd circuit elements. METHODS: Patients with chronic hemiparetic stroke (n = 15) were randomized to 2-weeks of Premotor Therapy or Motor Therapy, implemented through a robotic device. RESULTS: Overall, gains were modest but significant (change in FM score, 2.1 ± 2.8 points, p < 0.02) and did not differ by treatment assignment. However, a difference between Therapies was apparent when injury to the PMd circuit was considered, as the interaction between treatment assignment and degree of corticospinal tract injury was significantly related to the change in FM score (p = 0.018): the more the corticospinal tract was spared, the greater the gains provided by Premotor Therapy. Similar results were obtained when looking at the interaction between treatment assignment and PMd function (p = 0.03). CONCLUSIONS: Targeted engagement of a brain circuit is a feasible strategy for stroke rehabilitation. This approach has maximum impact when there is less stroke injury to key elements of the targeted circuit. Keywords: Stroke, premotor cortex, robot, motor recovery, corticospinal tract 1. Introduction Motor deficits are among the most common forms of impairment after stroke, present in > 80% of patients acutely (Rathore, Hinn, Cooper, Tyroler, & Rosamond, 2002). Most patients show spontaneous improvement in motor status during the weeks following stroke. Sev- eral forms of brain plasticity that contribute to this recovery have been identified (S. C. Cramer, 2008; Nudo, 2011). In particular, anatomical and functional ∗ Address for correspondence: Steven C. Cramer, MD, University of California, Irvine Medical Center, 200S. Manchester Ave. Suite 206, Orange, CA 92868, USA. Tel.: +1 714 456 6876; Fax: +1 714 456 8805; E-mail: scramer@uci.edu. evidence support a role for dorsal premotor cortex in support of return of motor function (Alagona et al., 2001; S. Cramer et al., 1997; Denny-Brown, 1950; Fries, Danek, Scheidtmann, & Hamburger, 1993; Gau- thier, Taub, Mark, Barghi, & Uswatte, 2012; Laplane, Talairach, Meininger, Bancaud, & Bouchareine, 1977; Seitz et al., 1998; Weiller, Chollet, Friston, Wise, & Frackowiak, 1992). Activity within ipsilesional dor- sal premotor cortex (PMd) has been associated with achieving spontaneous recovery (Fridman et al., 2004; Platz et al., 2000; Rehme, Eickhoff, Wang, Fink, & Grefkes, 2011; Sharma, Baron, & Rowe, 2009; Ward et al., 2006) as well as treatment-induced recovery (Carey et al., 2002; Johansen-Berg, Dawes, et al., 2002; 1053-8135/13/$27.50 © 2013 – IOS Press and the authors. All rights reserved