Stimulation targeting higher motor areas in stroke rehabilitation: A proof-of-concept, randomized, double-blinded placebo-controlled study of effectiveness and underlying mechanisms

Article type: Research Article

Authors: Cunningham, David A.^{a; b} | Varnerin, Nicole^a | Machado, Andre^c | Bonnett, Corin^a | Janini, Daniel^a | Roelle, Sarah^a | Potter-Baker, Kelsey^a | Sankarasubramanian, Vishwanath^a | Wang, Xiaofeng^d | Yue, Guang^e | Plow, Ela B.^{a; c; f; *}

Affiliations: [a] Department of Biomedical Engineering, Lerner Research Inst., Cleveland Clinic, Cleveland, OH, USA | [b] School of Biomedical Sciences, Kent State University, Kent, OH, USA | [c] Center for Neurological Restoration, Neurosurgery, Neurological Inst., Cleveland Clinic, Cleveland, OH, USA | [d] Department of Quantitative Health Sciences, Cleveland Clinic, OH, USA | [e] Human Performance & Engineering Laboratory, Kessler Foundation Research Center, West Orange, NJ, USA | [f] Department of Physical Medicine & Rehab, Neurological Inst., Cleveland Clinic, Cleveland, OH, USA

Correspondence: [*] Corresponding author: Ela B. Plow, PhD, PT, Assistant Staff, Biomedical Engineering, 9500 Euclid Ave, ND20, Cleveland Clinic, Cleveland, 44195 OH, USA. Tel.: +1 216 445 4589; Fax: +1 216 444 9198; E-mail: plowe2@ccf.org

Abstract: Purpose:To demonstrate, in a proof-of-concept study, whether potentiating ipsilesional higher motor areas (premotor cortex and supplementary motor area) augments and accelerates recovery associated with constraint induced movement. Methods:In a randomized, double-blinded pilot clinical study, 12 patients with chronic stroke were assigned to receive anodal transcranial direct current stimulation (tDCS) (n = 6) or sham (n = 6) to the ipsilesional higher motor areas during constraint-induced movement therapy. We assessed functional and neurophysiologic outcomes before and after 5 weeks of therapy. Results:Only patients receiving tDCS demonstrated gains in function and dexterity. Gains were accompanied by an increase in excitability of the contralesional rather than the ipsilesional hemisphere. Conclusions:Our proof-of-concept study provides early evidence that stimulating higher motor areas can help recruit the contralesional hemisphere in an adaptive role in cases of greater ipsilesional injury. Whether this early evidence of promise translates to remarkable gains in functional recovery compared to existing approaches of stimulation remains to be confirmed in large-scale clinical studies that can reasonably dissociate stimulation of higher motor areas from that of the traditional primary motor cortices.

Keywords: Stroke rehabilitation, transcranial direct current stimulation, constraint-induced movement therapy, premotor cortex, motor recovery, transcranial magnetic stimulation

DOI: 10.3233/RNN-150574

Journal: Restorative Neurology and Neuroscience, vol. 33, no. 6, pp. 911-926, 2015