Effectiveness and neural mechanisms associated with tDCS delivered to premotor cortex in stroke rehabilitation: study protocol for a randomized controlled trial

Trials

Andre Machado³  Ken Sakaie²  Xiao-Feng Wang⁶  Mark Lowe²  Guang H Yue¹  Corin Bonnett⁵  Alexandria Wyant³  Stephen Jones²  Erik Beall²  David A Cunningham⁵  Ela B Plow⁴ 

[1] Human Performance & Engineering Laboratory, Kessler Foundation Research Center, 1199 Pleasant Valley Way, West Orange, NJ, 07052, USA;Imaging Institute, Cleveland Clinic, 9500 Euclid Avenue, U15, Cleveland, OH, 44195, USA;Center for Neurological Restoration, Neurosurgery, Neurological Instt., Cleveland Clinic, 9500 Euclid Avenue, S31, Cleveland, OH, 44195, USA;Department of Physical Medicine & Rehab, Neurological Instt., Cleveland Clinic, Cleveland, OH, 44195, USA;Department of Biomedical Engineering, Lerner Research Instt., Cleveland Clinic, 9500 Euclid Avenue, ND20, Cleveland, OH, 44195, USA;Quantitative Health Sciences, Lerner Research Instt., Cleveland Clinic, 9500 Euclid Avenue, JJN3-01, Cleveland, OH, 44195, USA

关键词: Transcranial direct current stimulation (tDCS);    Transcranial magnetic stimulation (TMS);    Resting state functional magnetic resonance imaging (rs-fMRI);    Functional magnetic resonance imaging (fMRI);    Diffusion tensor imaging (DTI);    Premotor cortex (PMC);    Motor cortex (M1);    Brain stimulation;    Rehabilitation;    Stroke;   

Others  :  1092908
DOI  :  10.1186/1745-6215-14-331

 received in 2013-06-19, accepted in 2013-10-02,  发布年份 2013

【 摘 要 】

Background

More than 60% of stroke survivors experience residual deficits of the paretic upper limb/hand. Standard rehabilitation generates modest gains. Stimulation delivered to the surviving Primary Motor Cortex in the stroke-affected hemisphere has been considered a promising adjunct. However, recent trials challenge its advantage. We discuss our pilot clinical trial that aims to address factors implicated in divergent success of the approach. We assess safety, feasibility and efficacy of targeting an alternate locus during rehabilitation- the premotor cortex. In anticipating variance across patients, we measure neural markers differentiating response from non-response.

Methods/Design

In a randomized, sham-controlled, double-blinded pilot clinical study, patients with chronic stroke (n = 20) are assigned to receive transcranial direct current stimulation delivered to the premotor cortex or sham during rehabilitation of the paretic arm/hand. Patients receive the designated intervention for 30 min, twice a day for 3 days a week for 5 weeks. We assess hand function and patients’ reports of use of paretic hand. A general linear mixed methods model will analyze changes from pre- to post-intervention. Responders and non-responders will be compared upon baseline level of function, and neural substrates, including function and integrity of output tracts, bi-hemispheric balance, and lesion profile. Incidence of adverse events will be compared using Fisher’s Exact test, while rigor of blinding will be assessed with Chi-square analysis to ascertain feasibility.

Discussion

Variable success of cortical stimulation in rehabilitation can be related to gaps in theoretical basis and clinical investigation. Given that most patients with severe deficits have damage to the primary motor cortex or its output pathways, it would be futile to target stimulation to this site. We suggest targeting premotor cortex because it contributes substantially to descending output, a role that is amplified with greater damage to the motor cortex. With regards to clinical investigation, paired cortical stimulation in rehabilitation has been compared to rehabilitation alone in unblinded trials or to unconvincing sham conditions. Transcranial direct current stimulation, a noninvasive technique of brain stimulation, which offers a more effective placebo and has a favorable safety-feasibility profile, may improve scientific rigor. Neural markers of response would help inform patient selection for future clinical trials so we can address limitations of recent negative studies.

Trial registration

NCT01539096

【 授权许可】

   
2013 Plow et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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