Combined Neural and Behavioral Therapies to Enhance Stroke Recovery
Condition: Stroke
MeSH terms: Stroke
Study type: Interventional

Summary: 
      Stroke is the leading cause of long-term disability in this country with more than 1 million
      Americans reporting difficulty with daily activities. Loss of independence in self-care tasks
      is primarily due to limited recovery of the arm. This study will determine if the addition of
      Transcranial Magnetic Stimulation (TMS) to excite the lesioned hemisphere (side of the brain
      affected by the stroke), to progressive functional task exercise either of the weakened arm
      alone or of both arms together will improve arm recovery to a greater degree than one of
      these two types of arm exercise alone. Individuals post-stroke will participate in 16
      sessions of 1) arm rehabilitation alone (with the weaker arm only or with both arms together)
      or 2) arm rehabilitation plus TMS. The investigators will assess arm movement ability and
      function immediately following the 4-week intervention and at a 30-day follow-up to determine
      retention of immediate gains. The investigators hypothesize that those who receive TMS as an
      adjuvant will have improved arm movement ability than those who only exercise.
    

Detailed description: 
      Limited recovery of upper extremity (UE) function post-stroke continues to be one of the
      greatest challenges faced in neurorehabilitation. There is an urgent unmet need to identify
      effective approaches to drive UE recovery in this population. In response to this challenge,
      the overall purpose of this proposed research plan is to develop rehabilitation interventions
      that restore UE motor recovery. Contemporary approaches to motor rehabilitation are based on
      evidence that behavioral experience drives cortical reorganization following neural injury.
      Although the rationale of driving the damaged motor cortex by focused training of the paretic
      UE appears straightforward, and has historically been the focus of rehabilitation, functional
      recovery remains limited. There remains a gap between this central neurobiological change and
      a meaningful behavioral change. There is a need, therefore, to augment or potentiate
      behavioral experience. This proposal will address this gap by examining two potential drivers
      of the lesioned hemisphere: 1) the non-lesioned hemisphere via engagement of the unaffected
      UE in behavioral training and 2) stimulation of the lesioned hemisphere via repetitive
      Transcranial Magnetic Stimulation (rTMS). This proposal builds on the foundation of the
      applicant's previous work which suggested that the contralesional, intact, hemisphere could
      be used to drive the lesioned hemisphere through bimanual movement. Additionally, it is
      possible to drive the lesioned hemisphere externally using rTMS to enhance cortical
      stimulation. Thus, pairing externally-driven enhancement of cortical excitability with
      internally-driven activation of the intact hemisphere during bilateral movements could
      combine to further increase excitability in the lesioned hemisphere and manifest improved
      movement capability of the paretic UE. The fundamental hypothesis guiding this proposal is
      that increased excitability of the lesioned cortex will improve behavioral function of the
      paretic UE post-stroke. To investigate the overall hypothesis the investigators will examine
      these drivers of cortical excitability and their role in UE recovery by addressing the
      following aims:

      Specific Aim 1. Determine the magnitude of difference in central and behavioral changes in
      individuals with post-stroke hemiparesis randomized to a bilateral versus unilateral UE motor
      training program.

      Specific Aim 2a. Determine the magnitude of difference in central and behavioral changes in
      individuals with post-stroke hemiparesis randomized to behavioral UE training compared to
      behavioral UE training + rTMS.

      Specific Aim 2b. Determine the differential effects of rTMS on bilateral behavioral training
      compared to unilateral behavioral training as measured both centrally and behaviorally in
      individuals with post-stroke hemiparesis Post-stroke upper limb paresis and resultant loss of
      functional ability continues to present a barrier to those post-stroke in returning to full
      societal participation. Interventions that directly target the mechanism of hemiparesis,
      including decreased excitability of the lesioned hemisphere, are most likely to promote true
      recovery as opposed to the oft observed functional compensation in these individuals.
    

Intervention name(s): Real rTMS; Sham rTMS; Unimanual paretic UE Training
Intervention type(s): Procedure; Procedure; Procedure
Intervention description(s): rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses; sham rTMS application to lesioned hemisphere; 10 Hz, 1000 pulses; UE exercise for 4 hours (two hours 1:1 with therapist and two hours independent at home) for 16 sessions (4 sessions/week for 4 weeks)
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Rehabilitation; Neurophysiology; Upper Extremity