Background: Disability resulting from stroke and traumatic brain injury represent the main causes of long-term complications in adults. There are no universally accepted treatments available to treat these conditions and the financial, personal, familial and social cost of these disabilities cannot be underestimated. Preliminary data from different laboratories have shown that it is possible to modulate plastic processes in the lesioned brain by pharmacological, brain stimulation and somatosensory stimulation techniques. The purpose of this project is to identify mechanisms of stroke motor disability and characterize the most promising techniques to improve cortical plasticity in these patients to enhance functional recovery. Findings this year: From a pathophysiological point of view, we found in cerebellar stroke patients that short intracortical inhibition (SICI) was decreased in the contralesional primary motor cortex compared to ipsilesional M1 in the absence of side-to-side differences in healthy controls. These results document disinhibition of contralesional M1 in the chronic phase after cerebellar stroke. In patients with subcortical strokes (not involving the cerebellum), we found an abnormal persistence of SICI in the ipsilesional M1 during movement preparation that was absent in age-matched controls. Additionally, resting SICI was reduced in the patient group relative to controls. Altogether, these findings document deficient premovement modulation of intracortical inhibition in the ipsilesional M1 of patients with chronic stroke, an abnormality that might contribute to deficits in motor control of the paretic hand. We also investigated the neurophysiological mechanisms underlying training-dependent improvements in upper-extremity motor skills in stroke patients with substantial motor disability, the majority of stroke survivors. Preceding training, we found greater interhemispheric inhibition (measured by ipsilateral silent periods) in the affected triceps muscle, reflecting inhibition from the nonlesioned to the lesioned primary motor cortex in patients with more severe motor impairment. Training-induced improvements in reaching were greater in patients with slower response times at baseline. Increased motor evoked potential amplitudes and decreased silent periods were observed in the affected triceps but not in the biceps muscle after training. These results indicate that together with training-induced motor improvements, training-specific modulation of intra- and interhemispheric mechanisms occurs after reaching practice in chronic stroke patients with substantial arm impairment. We collaborated in an investigation on metabolites studied with MR spectroscopy in the primary motor cortex after stroke. It was shown that stroke survivors had lower N-acetylaspartate and higher myo-inositol levels across ipsi- and contralesional M1 compared with control subjects. Significant correlations between N-acetylaspartate and glutamate/glutamine were found in M1. Ipsilesional N-acetylaspartate and glutamate/glutamine were positively correlated with arm motor impairment and contralesional N-acetylaspartate with time after stroke. The results were interpreted as preliminary, suggesting significant alterations of neuronal-glial interactions in spared M1 with the ipsilesional alterations related to stroke severity and contralesional alterations to stroke duration. We have also implemented interventional trials in stroke patients. We participated in the first randomized parallel controlled trial assessing the feasibility, safety, and efficacy of virtual reality using Wii gaming technology in stroke rehabilitation;the results may serve as the basis for a larger multicenter trial. We determined that applying multiple sessions of somatosensory stimulation to the paretic limb could facilitate training effects on motor function after subacute stroke depending on the intensity of stimulation. It was proposed that careful dose-response studies are needed to optimize parameters of somatosensory stimulation before designing costly, larger double-blind multicenter clinical trials. Altogether, we advanced our understanding of the mechanisms underlying motor stroke disability and in the development of interventions that could facilitate functional recovery after chronic stroke.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Antal, A; Alekseichuk, I; Bikson, M et al. (2017) Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol 128:1774-1809
Boyd, Lara A; Hayward, Kathryn S; Ward, Nick S et al. (2017) Biomarkers of stroke recovery: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable. Int J Stroke 12:480-493
Harris-Love, Michelle L; Chan, Evan; Dromerick, Alexander W et al. (2016) Neural Substrates of Motor Recovery in Severely Impaired Stroke Patients With Hand Paralysis. Neurorehabil Neural Repair 30:328-38
Buch, Ethan R; Rizk, Sviatlana; Nicolo, Pierre et al. (2016) Predicting motor improvement after stroke with clinical assessment and diffusion tensor imaging. Neurology 86:1924-5
Saposnik, Gustavo; Cohen, Leonardo G; Mamdani, Muhammad et al. (2016) Efficacy and safety of non-immersive virtual reality exercising in stroke rehabilitation (EVREST): a randomised, multicentre, single-blind, controlled trial. Lancet Neurol 15:1019-27
Censor, Nitzan; Buch, Ethan R; Nader, Karim et al. (2016) Altered Human Memory Modification in the Presence of Normal Consolidation. Cereb Cortex 26:3828-37
Dayan, Eran; Thompson, Ryan M; Buch, Ethan R et al. (2016) 3D-printed head models for navigated non-invasive brain stimulation. Clin Neurophysiol 127:3341-2
Furlan, Leonardo; Conforto, Adriana Bastos; Cohen, Leonardo G et al. (2016) Upper Limb Immobilisation: A Neural Plasticity Model with Relevance to Poststroke Motor Rehabilitation. Neural Plast 2016:8176217
Liew, Sook-Lei; Rana, Mohit; Cornelsen, Sonja et al. (2016) Improving Motor Corticothalamic Communication After Stroke Using Real-Time fMRI Connectivity-Based Neurofeedback. Neurorehabil Neural Repair 30:671-5
Liew, Sook-Lei; Santarnecchi, Emilliano; Buch, Ethan R et al. (2014) Non-invasive brain stimulation in neurorehabilitation: local and distant effects for motor recovery. Front Hum Neurosci 8:378

Showing the most recent 10 out of 66 publications