Effects of high frequency rTMS of contralesional dorsal premotor cortex in severe subcortical chronic stroke: protocol of a randomized controlled trial with multimodal neuroimaging assessments

BACKGROUND: Previous studies have revealed that low frequency repeated transcranial magnetic stimulation (rTMS) on the contralesional primary motor cortex (cM1) is less effective in severe stroke patients with poor neural structural reserve than in patients with highly reserved descending motor pathway. This may be attributed to the fact that secondary motor cortex, especially contralesional dorsal premotor cortex (cPMd), might play an important compensatory role in the motor function recovery of severely affected upper extremity. The main purpose of this study is to compare the effectiveness of low frequency rTMS on cM1 and high frequency rTMS on cPMd in subcortical chronic stroke patients with severe hemiplegia. By longitudinal analysis of multimodal neuroimaging data, we hope to elucidate the possible mechanism of brain reorganization following different treatment regimens of rTMS therapy, and to determine the cut-off of stimulation strategy selection based on the degree of neural structural reserve. METHODS/DESIGN: The study will be a single-blinded randomized controlled trial involving a total of 60 subcortical chronic stroke patients with severe upper limb motor impairments. All patients will receive 3 weeks of conventional rehabilitation treatment, while they will be divided into three groups and receive different rTMS treatments: cM1 low frequency rTMS (n = 20), cPMd high frequency rTMS (n = 20), and sham stimulation group (n = 20). Clinical functional assessment, multimodal functional MRI (fMRI) scanning, and electrophysiological measurement will be performed before intervention, 3 weeks after intervention, and 4 weeks after the treatment, respectively. DISCUSSION: This will be the first study to compare the effects of low-frequency rTMS of cM1 and high-frequency rTMS of cPMd. The outcome of this study will provide a theoretical basis for clarifying the bimodal balance-recovery model of stroke, and provide a strategy for individualized rTMS treatment for stroke in future studies and clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900027399. Registered on 12 Nov 2019, http://www.chictr.org.cn/showproj.aspx?proj=43686.