Combined Transcranial Direct Current Stimulation and Motor Imagery-based Robotic Arm Training for Stroke Rehabilitation
Condition: Stroke
MeSH terms: Stroke
Study type: Interventional
Phase: Phase 2

Summary: 
      Stroke is the most common cause of adult disability. Current treatments for functional loss
      of the upper extremity post-stroke remain limited in efficacy, particularly for those with
      moderate to severe impairment.

      Previous studies have demonstrated the efficacy of transcranial direct current stimulation
      (tDCS) for motor recovery post-stroke, a technique of neuromodulation. Motor imagery is
      effective to enhance motor recovery, with activation of neural pathways similar to that of
      motor execution. This treatment is accessible to more severely impaired stroke survivors. Our
      previous studies have demonstrated feasibility and efficacy of motor imagery-based brain
      computer interface (MI-BCI) for post-stroke motor impairment, in which motor imagery is
      detected by surface EEG and translated to execution of the target movement with the aid of an
      arm robot (MIT-Manus).

      In this study, we investigate the feasibility of combining robot-assisted MI-BCI training,
      with tDCS to facilitate post-stroke motor recovery in moderate to severe impairment of upper
      extremity function. We hypothesise that both tDCS-BCI and sham-BCI will improve motor
      function in the stroke-affected arm; but that tDCS-BCI will be more effective than sham-BCI.
      Our secondary aim is to gain insight into the neurophysiological mechanism by comparing the
      cortical excitability changes following sham-BCI vs tDCS-BCI, using transcranial magnetic
      stimulation (TMS).

      We will conduct a randomized, double-blinded study with MI-BCI combined with tDCS (tDCS-BCI)
      vs MI-BCI combined with sham-tDCS (sham tDCS-BCI). Subjects will undergo 10 sessions of tDCS
      each lasting 20 minutes, followed by 40 minutes of robot-assisted MI-BCI training at each
      session. Primary outcome will be functional ability measured by upper extremity component of
      the Fugl-Meyer Assessment. Secondary outcome measures will be the Box & Block Test, Modified
      Ashworth Score (measuring spasticity), grip strength and measures of brain activity including
      transcranial magnetic stimulation (TMS) measures of magnetic resonance imaging (MRI) measures
      including functional MRI and diffusion tensor imaging (DTI).

      This study will be important to develop a new and effective treatment (tDCS-BCI) for
      post-stroke motor impairment.
    

Detailed description: 
      This is a randomised controlled trial of 32 subjects who have sustained their first ever
      subcortical stroke more than 9 months prior to study enrollment, with upper extremity
      impairment of 11-45 out of a maximum score of 66 on the Fugl-Meyer assessment scale.

      Subjects will be randomly allocated to one of the following 2 groups by using a
      computer-generated random sequence:

        1. 10 sessions over 2 weeks of MI-BCI training with 20 minutes of tDCS preceding training.

        2. 10 sessions over 2 weeks of MI-BCI training with 20 minutes of sham-tDCS preceding
           training.

      tDCS-BCI protocol Each of the 10 sessions of tDCS-BCI or sham-BCI will be conducted as
      follows: tDCS will be performed for 20 minutes immediately prior to each session of motor
      training. The anode will be placed over the M1 motor cortex of the affected hemisphere while
      the cathode will be placed over the unaffected M1.

      After initial calibration, MI-BCI training will involve MI of reaching tasks using the clock
      game interface of the MIT-Manus robotic system to perform multi-directional reaching
      movements. Upon detection of the intention to move towards the target on BCI, the robotic arm
      will complete the reaching movement towards the target. Each training session will last for
      40 minutes excluding set-up time and will be undertaken by a research assistant blinded to
      the condition of tDCS.

      Outcome measures Improvement in motor functional ability will be the main outcome of this
      study. Outcome measures will be assessed at the following time points: prior to treatment
      initiation, at week 2 (immediate post-training period) and week 6 (4 weeks after completion
      of training). A clinician blinded to the treatment condition will assess the effects of the
      intervention. Our primary outcome measure will be the upper extremity score of the Fugl-Meyer
      Assessment (FMA). This instrument measures upper extremity motor impairment including
      balance, coordination and speed. Secondary outcome measures for motor function will include
      (1) Box and Block Test: a timed test in which subjects are required to transfer 1-inch wooden
      blocks from one side of the box to another. It measures upper extremity manual dexterity and
      gross motor coordination. (2) Modified Ashworth Scale: is a 6-point measure of spasticity. We
      will assess the severity of spasticity at the shoulder, elbow, wrist and fingers. (3) Grip
      strength: will be measured using a hand-held dynamometer.In addition, we will monitor for
      adverse effects with a questionnaire documenting pain and discomfort at stimulation site,
      mood changes (using the Beck Depression Inventory), fatigue (using the Fatigue Severity
      Scale), and cognitive change (using the forward and backward digit span).Assessment of
      cortical excitability ? single and paired pulse TMS Another aim of this study is to
      investigate the mechanisms of this combined treatment on cortical plasticity as indexed by
      cortical excitability changes - assessed by single and paired pulse TMS. We will investigate
      the resting motor threshold, measured according to the technique of Rossini et al., 1994,
      before and after treatment, according to the schedule of outcome measures above; paired-pulse
      stimulation, measuring changes in intracortical facilitation and inhibition.

      MRI protocol Patients will be scanned at -2, 0 and 4 weeks to investigate short-term and
      medium-term changes in fMRI and DTI parameters following tDCS/BCI and sham/BCI treatment. A
      T1-weighted high-resolution scan and a set of axial fluid-attenuated inversion recovery
      images will be acquired. T1-weighted and fluid-attenuated inversion recovery images will be
      realigned and spatially normalized into images of isotropic voxel size implemented in
      Matlab.The data analysis will include image registration, estimation of diffusion tensor
      parameters including Apparent Diffusion Coefficient, Fractional Anisotropy, axial and radial
      diffusivities and tractography using Camino. Reversed phase encoding EPI distortion
      correction, and regression analysis of DTI, TMS and clinical findings will be performed using
      Matlab.For fMRI, images will be obtained during the resting state, active/passive hand
      movement and during imagined arm movement. For the imagined arm movement, subjects will be
      asked to watch a video on a screen to guide their performance of the imagined movement.
    

Intervention name(s): real-tDCS with MI-BCI
Intervention type(s): Device
Intervention description(s): As in Arm Description
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Stroke; Noninvasive brain stimulation; Brain-computer interface; Motor imagery; Rehabilitation