Invasive cortical stimulation to promote recovery of function after stroke: a critical appraisal.
OBJECTIVE
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.


RESULTS
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.
Berenson-Allen Center for Noninvasive Brain Stimulation, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Ela B
EB
Plow
James R
JR
Carey
Randolph J
RJ
Nudo
Alvaro
A
Pascual-Leone
D000818:Animals; D002540:Cerebral Cortex / Q000502:physiology*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004599:Electric Stimulation Therapy; D006801:Humans; D007858:Learning / Q000502:physiology; D008279:Magnetic Resonance Imaging; D009069:Movement Disorders / Q000209:etiology / Q000517:prevention & control / Q000534:rehabilitation; D009434:Neural Pathways / Q000473:pathology; D020521:Stroke / Q000150:complications / Q000628:therapy*; D000071939:Stroke Rehabilitation; D050781:Transcranial Magnetic Stimulation