Stroke Rehabilitation: A Case Study

With ~800,000 stroke cases every year in the United States, stroke is considered the major cause of disability in adults [1]. The ability of the brain to reorganize in response to pathological or environmental changes such as lesions is critically important to the recovery of motor function after stroke [2]. Re-establishment of ipsilesional cortical excitability has been associated with improved functional outcomes of the paretic limb following stroke [3,4]. Numerous approaches to modulate cortical excitability in stroke have been investigated. However, many involve the use of repetitive task practice with the affected hand which is not possible for severely impaired patients. Two promising approaches to modulate excitability of the ipsilesional hemisphere that do not require movement of the affected hand include paired associative stimulation (PAS) and mirror therapy. PAS is described as a peripheral nerve stimulation paired with transcranial magnetic stimulation (TMS) of primary motor cortex (M1) in a timing dependent manner to induce
Hebbian-like plasticity through collisions of afferent and efferent signals. Repetitive paired stimulation has been shown to induce bidirectional changes in M1 excitability depending on the interval between the peripheral and central stimulation [3].
Ipsilesional cortical excitability can also be enhanced with visuomotor illusions.
In mirror therapy, the illusion that movement of one hand is occurring on the opposite side, has been shown to activate the contralateral motor cortex in a task specific manner. Importantly, mirror therapy for stroke rehabilitation is reliant only on movement of the healthy hand making it appropriate for the most severely impaired individual [5].
In this study we will examine the effectiveness of combining the PAS and mirror therapy to induce a higher level of cortical excitability and/or longer lasting plasticity changes than either therapy in isolation. Modulation of cortical excitability will be evaluated over a period of 60 minutes after the therapy. We hypothesize that combining PAS and mirror therapy in one protocol (Mirror-PAS) will induce higher excitation and longer lasting excitation in motor cortex in healthy and stroke
subjects.
Specific Aim 1: To determine the optimal timing of triggering PAS over the ipsilateral motor cortex during a unilateral hand movement. Excitability of the ipsilateral M1 during contralateral hand movements is known to be modulated in response to the movement phase. Ipsilateral excitability is shown to be increased during movement execution [6]. Currently, the effect of PAS timing relative to the phase of contralateral hand movement on cortical excitability is unknown. Thus, it is crucial to investigate the appropriate timing of PAS triggering that assures the facilitation of the ipsilateral motor cortex. I will test the effect of different stimulation timings relative to the phase of the contralateral hand movement on ipsilateral cortical excitability assessed by TMS-elicited motor evoked potential (MEP) amplitude. This will test the hypothesis that triggering PAS during the execution phase of the contralateral hand movement facilitates the ipsilateral motor cortex.
Specific Aim 2: To determine the effectiveness of Mirror-PAS in inducing higher level of brain plasticity in the lesioned motor cortex than Mirror therapy or PAS alone. I will use the amplitude of TMS-elicited MEP prior and after the intervention as a direct measure to assess the change in motor cortex excitability. This will test the hypothesis that the Mirror-PAS intervention leads to plasticity changes represented as increase in the cortical excitability that is significantly higher and longer lasting than PAS or Mirror therapy separately.