Augmention the Effects of Mirror Therapy for Stroke Rehabilitation by tDCS

Approximately 30% to 66% of stroke survivors suffer from upper limb impairments 6 months after stroke leading to functional dependency and increased health care burden. Neurorehabilitation approaches and recently proposed neuromodulation are crucial in facilitating cortical reorganization, enhancing upper limb sensorimotor recovery, and improving functional independence to maximize activity participation and quality of life in patients with stroke. Mirror therapy (MT) has emerged as an effective treatment strategy for stroke rehabilitation. To augment the intervention effects of MT, combining MT with neuromodulation techniques, such as transcranial direct current stimulation (tDCS), to promote neuroplasticity is an appealing approach. However, how tDCS may be applied in conjunction with MT to achieve improved outcomes remains undetermined. The long-term goal of this proposed project is to identify the optimal combination of MT and tDCS to ameliorate disability and enhance quality of life in patients with stroke. This project will also investigate the possible mechanisms and potential predictors of treatment success for the hybrid regimen. Four specific aims have been identified for this project. The first is to compare the effect of tDCS stimulation timing and location on augmenting the effects of MT. The tDCS will be applied before or concurrently with MT and will be applied over the primary motor cortex (M1) or premotor cortex (PMC). Outcome measures will include behavioral performance, electroencephalography (EEG) physiological measures, and kinematic parameters of arm movement control. The second aim is to determine whether the treatment effects can be retained for 3 or 6 months after intervention. The third aim is to explore whether patients with M1 involved will respond to treatments differently from those without M1 involved. The fourth aim is to identify the characteristics of patients who respond favorably to the hybrid therapy. In this 5-year project, we will conduct a randomized, placebo-controlled clinical trial with 140 patients with stroke to be recruited from 2 hospitals. Eligible participants will be randomly assigned to 1 of 5 intervention groups: (1) tDCS applied over the ipsilesional M1 before MT, (2) tDCS applied over ipsilesional M1 concurrently with MT, (3) tDCS applied over the ipsilesional PMC before MT, (4) tDCS applied over the ipsilesional PMC concurrently with MT, and (5) MT with sham tDCS. All participants will receive 20 treatment sessions (90 minutes/day, 5 days/week, for 4 consecutive weeks). The certified therapist(s) will be trained by the primary investigator to ensure the competency of implementing the rehabilitation protocols. Evaluators, blinded to group allocation, will be trained to assess the participants before, immediately after, at 3 months, and 6 months after intervention. The behavioral assessments will be conducted at all 4 time points, but the EEG physiological and kinematic measures will only be assessed before and immediately after intervention. Behavioralmeasures at the impairment, activity and participation levels, will include the Fugl-Meyer Assessment, Modified Ashworth Scale, MyotonPro, Revised Nottingham Sensory Assessment, Stroop Color-Word Test, a dual-task test, the Wolf Motor Function Test, Motor Activity Log, the actigraphy, ABILHAND Questionnaire, the Nottingham Extended Activities of Daily Living Scale, and the Stroke Impact Scale Version 3.0. EEG physiological measures indicating the cortical excitability will be assessed with the EEG device during a task of reaching to press the button. Movement kinematics will be assessed during unilateral and bilateral forward reaching and reach-to-grasp, if capable, movements. Two-way repeated measures analysis of variance followed by the Bonferroni post hoc test will be used to evaluate the treatment effects among the 5 groups. The effect size of partial 2 will be calculated to identify the magnitude of performance changes. Two-way repeated measures analysis of variance or the Friedman test will be used for subsequent analysis to determine whether the M1 lesion will influence the treatment effects at different times for each group. To determine the characteristics of good responders for the hybrid therapy, multicollinearity of the potential predictors will be examined and multiple linear regression analyses will be conducted. This research will provide scientific evidence for the effects of neurorehabilitation hybridized with neuromodulation. Specifically, the findings will elucidate the fundamental parameters of tDCS application in conjunction with MT. In addition, potential electrophysiological and biomechanical mechanisms associated with the hybrid therapy can be determined, and the characteristics of patients who may respond to the treatment will be identified. The overall research results will bridge the research gap of basic science and clinical rehabilitation and can thus maximize motor and functional recovery after stroke.

Project ID:PG10701-0091
External Project ID:NHRI-EX107-10604PI