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      An investigation of cortical neuroplasticity following stroke in adults: is there evidence for a critical window for rehabilitation?

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          Abstract

          Background

          Evidence in animal stroke models suggests that neuroplasticity takes place maximally in a specific time window after an ischaemic lesion, which may coincide with the optimal time to intervene with rehabilitation. The aim of this study is to investigate neurophysiological evidence for a “critical window” of enhanced neuroplasticity in patients following ischaemic stroke, and establish its duration. We will also investigate changes in cortical inhibition following stroke, and the influence this has on functional recovery.

          Methods/Design

          We will recruit participants recently admitted to the Stroke Unit of major metropolitan hospitals who have had a stroke and can provide informed consent. Participants will be excluded if they have any contraindications to Transcranial Magnetic Stimulation. We will compare neurophysiological outcomes in an age-matched healthy control group. We conservatively hypothesise a 5 % increase in neuroplasticity at the optimal timing following stroke, compared to control participants, and require 43 patients following stroke to detect a significant difference with 80 % power. The primary outcome is the change in the motor evoked potential (MEP) amplitude in a hand muscle, after the administration of a plasticity-inducing paradigm to the affected hemisphere. Secondary outcomes include measures of cortical excitability, intracortical inhibition and arm function.

          Discussion

          The data from this trial will clarify whether there is a critical window for neuroplastic change in the brain following stroke. If so, intensive rehabilitation during this period could be more effective, reducing long-term disability and the cost burden of stroke.

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          Most cited references24

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          Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research.

          This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7-9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible.
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            Neural correlates of motor recovery after stroke: a longitudinal fMRI study.

            Recovery of motor function after stroke may occur over weeks or months and is often attributed to cerebral reorganization. We have investigated the longitudinal relationship between recovery after stroke and task-related brain activation during a motor task as measured using functional MRI (fMRI). Eight first-ever stroke patients presenting with hemiparesis resulting from cerebral infarction sparing the primary motor cortex, and four control subjects were recruited. Subjects were scanned on a number of occasions whilst performing an isometric dynamic visually paced hand grip task. Recovery in the patient group was assessed using a battery of outcome measures at each time point. Task-related brain activations decreased over sessions as a function of recovery in a number of primary and non-primary motor regions in all patients, but no session effects were seen in the controls. Furthermore, consistent decreases across sessions correlating with recovery were seen across the whole patient group independent of rate of recovery or initial severity, in primary motor cortex, premotor and prefrontal cortex, supplementary motor areas, cingulate sulcus, temporal lobe, striate cortex, cerebellum, thalamus and basal ganglia. Although recovery-related increases were seen in different brain regions in four patients, there were no consistent effects across the group. These results further our understanding of the recovery process by demonstrating for the first time a clear temporal relationship between recovery and task-related activation of the motor system after stroke.
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              Brain representation of active and passive movements.

              During active and passive (driven by a torque motor) flexion and extension of the right elbow, regional cerebral blood flow (rCBF) was measured in six healthy, male volunteers using positron emission tomography and the standard H2(15)O injection technique. During active as well as during passive movements of the right elbow there were strong increases in rCBF, identical in location, amount, and extent in the contralateral sensorimotor cortex. There were activations during both conditions in the supplementary motor area (stronger and more inferior in the active condition) and inferior parietal cortex (on the convexity during active movements and in the depth of the central sulcus during passive movements). During active movements only, activations of the basal ganglia and the cingulate gyrus were found. Brain activations during motor tasks are largely related to the processing of afferent information.
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                Author and article information

                Contributors
                +61 8 83021684 , michelle.mcdonnell@unisa.edu.au
                simon.koblar@adelaide.edu.au
                n.ward@ucl.ac.uk
                j.rothwell@ucl.ac.uk
                brenton.hordacre@adelaide.edu.au
                michael.ridding@adelaide.edu.au
                Journal
                BMC Neurol
                BMC Neurol
                BMC Neurology
                BioMed Central (London )
                1471-2377
                11 July 2015
                11 July 2015
                2015
                : 15
                : 109
                Affiliations
                [ ]Alliance for Research in Exercise, Nutrition and Activity and International Centre for Allied Health Evidence, Sansom Institute for Health Research, School of Health Sciences, University of South Australia, GPO Box 2471, Adelaide, SA 5001 Australia
                [ ]Stroke Research Programme, School of Medicine, South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia
                [ ]Sobell Department of Motor Neuroscience, University College London Institute of Neurology, Queen Square, London, England
                [ ]UCLP Centre For Neurorehabilitation, Queen Square, London, England
                [ ]The National Hospital for Neurology and Neurosurgery, Queen Square, London, England
                [ ]Neuromotor Plasticity and Development Research Group, Robinson Research Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia
                Article
                356
                10.1186/s12883-015-0356-7
                4702414
                26162759
                a5e8778f-ab0f-40cd-85e9-5a95779dd45a
                © McDonnell et al. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 May 2015
                : 18 June 2015
                Categories
                Study Protocol
                Custom metadata
                © The Author(s) 2015

                Neurology
                stroke,neuroplasticity,critical window
                Neurology
                stroke, neuroplasticity, critical window

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