Objective: Motor recovery after stroke depends on the integrity of ipsilesional motor circuits and interactions between the ipsilesional and contralesional hemispheres. In this sham-controlled randomized trial, we investigated whether noninvasive modulation of regional excitability of bilateral motor cortices in combination with physical and occupational therapy improves motor outcome after stroke. Methods:Twenty chronic stroke patients were randomly assigned to receive 5 consecutive sessions of either 1) bihemispheric transcranial direct current stimulation (tDCS) (anodal tDCS to upregulate excitability of ipsilesional motor cortex and cathodal tDCS to downregulate excitability of contralesional motor cortex) with simultaneous physical/occupational therapy or 2) sham stimulation with simultaneous physical/occupational therapy. Changes in motor impairment (Upper Extremity Fugl-Meyer) and motor activity (Wolf Motor Function Test) assessments were outcome measures while functional imaging parameters were used to identify neural correlates of motor improvement.

Background— Percutaneous aortic valve replacement is a new emerging technology for interventional treatment of severe aortic valve stenosis in surgical high-risk patients. This study was intended to provide a summary of the development and current safety and efficacy status of the self-expanding CoreValve Revalving prosthesis. Method and Results— Between 2005 and 2008, we have enrolled 136 consecutive patients with percutaneous aortic valve replacement using the CoreValve prosthesis. In this prospective nonrandomized, single-center trial, we analyzed procedural outcome, complications and clinical status up to 1 year. First, second, and third generation of the CoreValve prosthesis were implanted in 10, 24, and 102 consecutive high-risk patients (logistic EuroScore: 23.1�15.0%) with severe symptomatic aortic valve stenosis. Mean transvalvular pressure gradient was 41.5�16.7 mm Hg. The procedural success rate increased from generation 1/2 to 3 from 70.0%/70.8% to 91.2% ( P =0.003). The 30-day combined rate of death/stroke/myocardial infarction was 40.0%/20.8%/14.7% ( P =0.11) for generation 1, 2, and 3, with no procedural death in generation 3. Pressure gradients improved significantly with a final mean gradient of 8.1�3.8 mm Hg. Overall functional status assessed by New York Heart Association class improved from 3.3�0.5 (pre) to 1.7�0.7 (post) ( P <0.001) and remained stable in the follow-up. Conclusion— In experienced hands, percutaneous aortic valve replacement with the CoreValve system for selected patients with severe aortic valve stenosis has a high acute success rate associated with a low periprocedural mortality/stroke rate as well as remarkable clinical and hemodynamic improvements, which persist over time. Additional studies are now required to confirm these findings, particularly head-to-head comparisons with surgical valve replacement in different risk populations.

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Transcranial direct current stimulation over the left motor area influenced both contralateral and ipsilateral finger sequence movements in seven healthy adults. Effects for the two hands were reversed: anodal stimulation improved right-hand performance significantly more than cathodal stimulation, whereas cathodal stimulation improved left-hand performance significantly more than anodal stimulation. The results show that stimulating a motor region directly, or indirectly by modulating activity in the homologous region on the opposite hemisphere, can affect motor skill acquisition, presumably by facilitating effective synaptic connectivity. This outcome provides evidence for the role of interhemispheric inhibition in corticomotor functioning, and also has implications for treatment methods aimed at facilitating motor recovery after stroke.

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We studied motor representation in patients who recovered well following a stroke. Eighteen righthanded stroke patients and eleven age-matched control subjects underwent functional Magnetic Resonance Imaging (fMRI) while performing unimanual index finger (abduction-adduction) and wrist movements (flexion-extension) using their recovered and non-affected hand. A subset of these patients underwent Transcranial Magnetic Stimulation (TMS) to elicit motor evoked potentials (MEP) in the first dorsal interosseous muscle of both hands. Imaging results suggest that good recovery utilizes both ipsi-and contralesional resources, although results differ for wrist and index finger movements. Wrist movements of the recovered arm resulted in significantly greater activation of the contralateral (lesional) and ipsilateral (contralesional) primary sensorimotor cortex (SM1), while comparing patients to control subjects performing the same task. In contrast, recovered index finger movements recruited a larger motor network, including the contralateral SM1, Supplementary Motor Area (SMA) and cerebellum when patients were compared to control subjects. TMS of the lesional hemisphere but not of the contralesional hemisphere induced MEPs in the recovered hand. TMS parameters also revealed greater transcallosal inhibition, from the contralesional to the lesional hemisphere than in the reverse direction. Disinhibition of the contralesional hemisphere observed in a subgroup of our patients suggests persistent alterations in intracortical and transcallosal (interhemispheric) interactions, despite complete functional recovery.

We modulated neural excitability in the human motor cortex to investigate behavioral effects for both hands. In a previous study, we showed that decreasing excitability in the dominant motor cortex led to a decline in performance for the contralateral hand and an improvement for the ipsilateral hand; increasing excitability produced the opposite effects. Research suggests that the ipsilateral effects were mediated by interhemispheric inhibition. Physiological evidence points to an asymmetry in interhemispheric inhibition between the primary motor cortices, with stronger inhibitory projections coming from the dominant motor cortex. In the present study, we examined whether there is a hemispheric asymmetry in the effects on performance when modulating excitability in the motor cortex. Anodal and cathodal transcranial direct current stimulation were applied to the motor cortex of 17 participants, targeting the non-dominant hemisphere on one day and the dominant hemisphere on another day, along with one sham session. Participants performed a finger-sequence coordination task with each hand before and after stimulation. The dependent variable was calculated as the percentage of change in the number of correct keystrokes. We found that the effects of transcranial direct current stimulation depended upon which hemisphere was stimulated; modulating excitability in the dominant motor cortex significantly affected performance for the contralateral and ipsilateral hands, whereas modulating excitability in the non-dominant motor cortex only had a significant impact for the contralateral hand. These results provide evidence for a hemispheric asymmetry in the ipsilateral effects of modulating excitability in the motor cortex and may be important for clinical research on motor recovery.

Purpose It is thought that following a stroke the contralesional motor region exerts an undue inhibitory influence on the lesional motor region which might limit recovery. Pilot studies have shown that suppressing the contralesional motor region with cathodal transcranial Direct Current Stimulation (tDCS) can induce a short lasting functional benefit; greater and longer lasting effects might be achieved with combining tDCS with simultaneous occupational therapy (OT) and applying this intervention for multiple sessions. Methods We carried out a randomized, double blind, sham controlled study of chronic stroke patients receiving either 5 consecutive days of cathodal tDCS (for 30 minutes) applied to the contralesional motor region and simultaneous OT, or sham tDCS+OT. Results We showed that cathodal tDCS+OT resulted in significantly more improvement in Range-Of-Motion in multiple joints of the paretic upper extremity and in the Upper-Extremity Fugl-Meyer scores than sham tDCS+OT, and that the effects lasted at least one week post-stimulation. Improvement in motor outcome scores was correlated with decrease in fMRI activation in the contralesional motor region exposed to cathodal stimulation. Conclusions This suggests that cathodal tDCS combined with OT leads to significant motor improvement after stroke due to a decrease in the inhibitory effect that the contralesional hemisphere exerts onto the lesional hemisphere.