Transcranial direct current stimulation over the motor and premotor cortex with mirror therapy improves motor control, muscle function, and brain activity in chronic stroke: a double-blind randomized sham-controlled trial

BACKGROUND: Transcranial direct current stimulation (tDCS) is a popular approach to augment the effects of neurorehabilitation. Most studies stimulated the ipsilesional primary motor cortex (iM1); nonetheless, the success of iM1 stimulation was variable, suggesting that it may not be optimal for improving recovery. Ipsilesional premotor cortex (iPMC) may be an alternative candidate based on its likelihood of survival post-stroke and its contribution to functions. This study aimed to determine the effects of tDCS on the iPMC and iM1 with mirror therapy (MT) on motor control, muscle function, and brain activity in chronic stroke. METHODS: Thirty-six participants were randomly distributed into (1) iPMC-tDCS with MT (PMC) (2), iM1-tDCS with MT (M1), and (3) sham tDCS with MT (sham). Motor control was assessed using kinematics. Muscle function was assessed using the modified Ashworth and the Medical Research Council Scales. The M1 and PMC activity was recorded using electroencephalography (EEG), and the event-related desynchronization and the laterality index (LI) were examined. RESULTS: Significant within-group differences were identified in the kinematic outcomes. After interventions, the PMC group showed reduced paretic upper limb muscle spasticity and improved paretic limb control with greater movement smoothness and peak velocity. The M1 group showed reduced trunk compensation with fewer trunk displacement and flexion. However, the sham group relied more on trunk compensation, demonstrating increased trunk peak velocity and smoothness. Significant between-group differences were also found in paretic limb control and trunk displacement. Post-hoc analysis revealed that the PMC group improved paretic limb control, and the M1 group showed reduced trunk displacement more than the sham group. Significant within-and between-group differences were identified in EEG outcomes. The iM1 and contralesional PMC (cPMC) activity increased from pre-to-post intervention in the M1 group. In contrast, the iM1 activity decreased, and the LI declined from pre- to post-intervention in the sham group. Significant group differences were found in the iM1 activity, with the PMC and M1 having greater iM1 activation than the sham group. CONCLUSIONS: Differential treatment benefits were identified between iPMC- and iM1-tDCS with MT. iPMC-tDCS with MT uniquely improved paretic upper limb control with reduced muscle spasticity while iM1-tDCS with MT mitigated trunk compensation during reaching. These findings suggest that both iPMC- and iM1-tDCS could augment the effects of stroke neurorehabilitation and may be considered in clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04655209. Registered on 15th November 2020. https://clinicaltrials.gov/study/NCT04655209 .