Stimulation targeting higher motor areas in stroke rehabilitation: A proof-of-concept, randomized, double-blinded placebo-controlled study of effectiveness and underlying mechanisms.
OBJECTIVE
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.
Department of Biomedical Engineering, Lerner Research Inst., Cleveland Clinic, Cleveland, OH, USA.|School of Biomedical Sciences, Kent State University, Kent, OH, USA.
David A
DA
Cunningham
Department of Biomedical Engineering, Lerner Research Inst., Cleveland Clinic, Cleveland, OH, USA.
Nicole
N
Varnerin
Center for Neurological Restoration, Neurosurgery, Neurological Inst., Cleveland Clinic, Cleveland, OH, USA.
Andre
A
Machado
Department of Biomedical Engineering, Lerner Research Inst., Cleveland Clinic, Cleveland, OH, USA.
Corin
C
Bonnett
Department of Biomedical Engineering, Lerner Research Inst., Cleveland Clinic, Cleveland, OH, USA.
Daniel
D
Janini
Department of Biomedical Engineering, Lerner Research Inst., Cleveland Clinic, Cleveland, OH, USA.
Sarah
S
Roelle
Department of Biomedical Engineering, Lerner Research Inst., Cleveland Clinic, Cleveland, OH, USA.
Kelsey
K
Potter-Baker
Department of Biomedical Engineering, Lerner Research Inst., Cleveland Clinic, Cleveland, OH, USA.
Vishwanath
V
Sankarasubramanian
Department of Quantitative Health Sciences, Cleveland Clinic, OH, USA.
Xiaofeng
X
Wang
Human Performance & Engineering Laboratory, Kessler Foundation Research Center, West Orange, NJ, USA.
Guang
G
Yue
Department of Biomedical Engineering, Lerner Research Inst., Cleveland Clinic, Cleveland, OH, USA.|Center for Neurological Restoration, Neurosurgery, Neurological Inst., Cleveland Clinic, Cleveland, OH, USA.|Department of Physical Medicine & Rehab, Neurological Inst., Cleveland Clinic, Cleveland, OH, USA.
Ela B
EB
Plow
D000368:Aged; D004311:Double-Blind Method; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000473:pathology / Q000503:physiopathology*; D009048:Motor Skills / Q000502:physiology; D026201:Musculoskeletal Manipulations / Q000379:methods*; D010865:Pilot Projects; D011379:Prognosis; D020127:Recovery of Function / Q000502:physiology; D020521:Stroke / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology*; D000071939:Stroke Rehabilitation; D065908:Transcranial Direct Current Stimulation / Q000379:methods*; D050781:Transcranial Magnetic Stimulation; D016896:Treatment Outcome
Stroke rehabilitation; constraint-induced movement therapy; motor recovery; premotor cortex; transcranial direct current stimulation; transcranial magnetic stimulation