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Published Online
on April 9, 2009

Stroke. 2009
Published online before print April 9, 2009, doi: 10.1161/STROKEAHA.108.540823
A more recent version of this article appeared on May 1, 2009
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Submitted on October 23, 2008
Revised on December 10, 2008
Accepted on January 6, 2009

Invasive Cortical Stimulation to Promote Recovery of Function After Stroke. A Critical Appraisal

Ela B. Plow PhD, PT; James R. Carey PhD, PT; Randolph J. Nudo PhD; and Alvaro Pascual-Leone MD, PhD*

From the Berenson-Allen Center for Noninvasive Brain Stimulation (E.B.P., A.P.-L.), Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Mass; the Program in Physical Therapy (J.R.C.), University of Minnesota, Minneapolis, Minn; the Landon Center on Aging and Department of Molecular and Integrative Physiology (R.J.N.), University of Kansas Medical Center, Kansas City, Kan; and Instituto Guttmann de Neurorrehabilitación (A.P.-L.), Universidad Autónoma de Barcelona, Badalona, España.

* To whom correspondence should be addressed. E-mail: apleone{at}bidmc.harvard.edu.

Background and Purpose—Residual motor deficits frequently linger after stroke. Search for newer effective strategies to promote functional recovery is ongoing. Brain stimulation, as a means of directing adaptive plasticity, is appealing. Animal studies and Phase I and II trials in humans have indicated safety, feasibility, and efficacy of combining rehabilitation and concurrent invasive cortical stimulation. However, a recent Phase III trial showed no advantage of the combination. We critically review results of various trials and discuss the factors that contributed to the distinctive result.

Summary of Review—Regarding cortical stimulation, it is important to determine the (1) location of peri-infarct representations by integrating multiple neuroanatomical and physiological techniques; (2) role of other mechanisms of stroke recovery; (3) viability of peri-infarct tissue and descending pathways; (4) lesion geometry to ensure no alteration/displacement of current density; and (5) applicability of lessons generated from noninvasive brain stimulation studies in humans. In terms of combining stimulation with rehabilitation, we should understand (1) the principle of homeostatic plasticity; (2) the effect of ongoing cortical activity and phases of learning; and (3) that subject-specific intervention may be necessary.

Conclusions—Future cortical stimulation trials should consider the factors that may have contributed to the peculiar results of the Phase III trial and address those in future study designs.


Key words: electrical stimulation of the brain • neuronal plasticity • recovery of function • stroke rehabilitation