CIMT as a behavioral engine in research on physiological adjuvants to neurorehabilitation: The challenge of merging animal and human research

Issue title: Constraint-Induced Movement therapy

Guest editors: Edward Taubx and Gitendra Uswattey

Article type: Research Article

Authors: Nadeau, Stephen E.^{a; b; c; d; *} | Wu, Samuel S.^{a; b; e}

Affiliations: [a] Brain Rehabilitation Research Center, Malcom Randall Department of Veterans Affairs Medical Center, Gainesville, FL, USA | [b] Rehabilitation Outcomes Research Center, Malcom Randall Department of Veterans Affairs Medical Center, Gainesville, FL, USA | [c] Geriatric Research, Education and Clinical Center, Malcom Randall Department of Veterans Affairs Medical Center, Gainesville, FL, USA | [d] Department of Neurology, University of Florida College of Medicine, Gainesville, FL, USA | [e] Department of Statistics, University of Florida College of Medicine, Gainesville, FL, USA | [x] Department of Psychology, School of Social & Behavioral Sciences, University of Alabama at Birmingham, AL, USA | [y] Department of Physical Therapy, School of Health Related Professions, University of Alabama at Birmingham, AL, USA

Correspondence: [*] Address for correspondence: Stephen E. Nadeau, M.D., GRECC (182), Malcom Randall DVA Medical Center, 1601 SW Archer Road, Gainesville, FL 32608-1197, USA. Tel.: +1 352 374 6114; Fax: +1 352 374 6142; E-mail: [email protected]

Abstract: A physiological adjuvant to neuroplasticity cannot put new knowledge into the brain – it can only augment behavioral rehabilitation, which does replace knowledge in the brain lost due to injury. Clinical trials of adjuvant agents should therefore incorporate behavioral engines: behavioral therapies that have a potent effect and minimize error variance due to variability in subject attributes and the administration of the therapy. We consider in some detail the attributes of behavioral engines with a particular focus on constraint induced movement therapy. Human trials of physiological adjuvants to neuroplasticity are predicated on discoveries from animal research. Because human trials are expensive and carry risk of injury, it behooves us to lay a comprehensive foundation for these trials with animal studies (also incorporating behavioral engines) and to carefully mesh animal and clinical work. We review in detail our own and others' work involving human subjects with brain lesions and animal models of brain injury using donepezil, a central acetyl cholinesterase inhibitor, d-cycloserine, a partial agonist at the NMDA receptor glycine site, d-amphetamine, and methylphenidate in an effort to elucidate the strengths and weakness of animal and human neurorehabilitation science with respect to this mesh between animal and human subject research. We consider modifications in current approaches that might more efficiently advance neurorehabilitation science.

Keywords: Constraint induced movement therapy, hemiparesis, rehabilitation, donepezil, cycloserine, amphetamine, stroke

DOI: 10.3233/NRE-2006-21203

Journal: NeuroRehabilitation, vol. 21, no. 2, pp. 107-130, 2006