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      Repetitive transcranial magnetic stimulation in stroke rehabilitation: review of the current evidence and pitfalls

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          Abstract

          Acute brain ischemia causes changes in several neural networks and related cortico-subcortical excitability, both in the affected area and in the apparently spared contralateral hemisphere. The modulation of these processes through modern techniques of noninvasive brain stimulation, namely repetitive transcranial magnetic stimulation (rTMS), has been proposed as a viable intervention that could promote post-stroke clinical recovery and functional independence. This review provides a comprehensive summary of the current evidence from the literature on the efficacy of rTMS applied to different clinical and rehabilitative aspects of stroke patients. A total of 32 meta-analyses published until July 2019 were selected, focusing on the effects on motor function, manual dexterity, walking and balance, spasticity, dysphagia, aphasia, unilateral neglect, depression, and cognitive function after a stroke. Only conventional rTMS protocols were considered in this review, and meta-analyses focusing on theta burst stimulation only were excluded. Overall, both HF-rTMS and LF-rTMS have been shown to be safe and well-tolerated. In addition, the current literature converges on the positive effect of rTMS in the rehabilitation of all clinical manifestations of stroke, except for spasticity and cognitive impairment, where definitive evidence of efficacy cannot be drawn. However, routine use of a specific paradigm of stimulation cannot be recommended yet due to a significant level of heterogeneity of the studies in terms of protocols to be set and outcome measures that have to be used. Future studies need to preliminarily evaluate the most promising protocols before going on to multicenter studies with large cohorts of patients in order to achieve a definitive translation into daily clinical practice.

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          Most cited references 116

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          Cortical plasticity: from synapses to maps.

          It has been clear for almost two decades that cortical representations in adult animals are not fixed entities, but rather, are dynamic and are continuously modified by experience. The cortex can preferentially allocate area to represent the particular peripheral input sources that are proportionally most used. Alterations in cortical representations appear to underlie learning tasks dependent on the use of the behaviorally important peripheral inputs that they represent. The rules governing this cortical representational plasticity following manipulations of inputs, including learning, are increasingly well understood. In parallel with developments in the field of cortical map plasticity, studies of synaptic plasticity have characterized specific elementary forms of plasticity, including associative long-term potentiation and long-term depression of excitatory postsynaptic potentials. Investigators have made many important strides toward understanding the molecular underpinnings of these fundamental plasticity processes and toward defining the learning rules that govern their induction. The fields of cortical synaptic plasticity and cortical map plasticity have been implicitly linked by the hypothesis that synaptic plasticity underlies cortical map reorganization. Recent experimental and theoretical work has provided increasingly stronger support for this hypothesis. The goal of the current paper is to review the fields of both synaptic and cortical map plasticity with an emphasis on the work that attempts to unite both fields. A second objective is to highlight the gaps in our understanding of synaptic and cellular mechanisms underlying cortical representational plasticity.
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            Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex.

            We applied trains of focal, rapid-rate transcranial magnetic stimulation (rTMS) to the motor cortex of 14 healthy volunteers with recording of the EMG from the contralateral abductor pollicis brevis, extensor carpi radialis, biceps brachii and deltoid muscles. Modulation of the amplitude of motor evoked potentials (MEPs) produced in the target muscle during rTMS showed a pattern of inhibitory and excitatory effects which depended on the rTMS frequency and intensity. With the magnetic coil situated over the optimal scalp position for activating the abductor pollicis brevis, rTMS led to spread of excitation, as evident from the induction of progressively larger MEPs in the other muscles. The number of pulses inducing this spread of excitation decreased with increasing rTMS frequency and intensity. Latency of the MEPs produced in the other muscles during the spread of excitation was significantly longer than that produced by single-pulse TMS applied to the optimal scalp positions for their activation. The difference in MEP latency could be explained by a delay in intracortical conduction along myelinated cortico-cortical pathways. Following rTMS, a 3-4 min period of increased excitability was demonstrated by an increase in the amplitude of MEPs produced in the target muscles by single-pulse TMS. Nevertheless, repeated rTMS trains applied 1 min apart led to similar modulation of the responses and to spread of excitation after approximately the same number of pulses. This suggests that the spread might be due to the breakdown of inhibitory connections or the recruitment of excitatory pathways, whereas the post-stimulation facilitation may be due to a transient increase in the efficacy of excitatory synapses.
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              Modulation of brain plasticity in stroke: a novel model for neurorehabilitation.

              Noninvasive brain stimulation (NIBS) techniques can be used to monitor and modulate the excitability of intracortical neuronal circuits. Long periods of cortical stimulation can produce lasting effects on brain function, paving the way for therapeutic applications of NIBS in chronic neurological disease. The potential of NIBS in stroke rehabilitation has been of particular interest, because stroke is the main cause of permanent disability in industrial nations, and treatment outcomes often fail to meet the expectations of patients. Despite promising reports from many clinical trials on NIBS for stroke recovery, the number of studies reporting a null effect remains a concern. One possible explanation is that the interhemispheric competition model--which posits that suppressing the excitability of the hemisphere not affected by stroke will enhance recovery by reducing interhemispheric inhibition of the stroke hemisphere, and forms the rationale for many studies--is oversimplified or even incorrect. Here, we critically review the proposed mechanisms of synaptic and functional reorganization after stroke, and suggest a bimodal balance-recovery model that links interhemispheric balancing and functional recovery to the structural reserve spared by the lesion. The proposed model could enable NIBS to be tailored to the needs of individual patients.
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                Author and article information

                Contributors
                Journal
                Ther Adv Neurol Disord
                Ther Adv Neurol Disord
                TAN
                sptan
                Therapeutic Advances in Neurological Disorders
                SAGE Publications (Sage UK: London, England )
                1756-2856
                1756-2864
                25 September 2019
                2019
                : 12
                Affiliations
                Department of Medical and Surgical Sciences and Advanced Technologies, Section of Neurosciences, University of Catania, Catania, Italy
                Department of Surgery and Medical-Surgery Specialties, University of Catania, Via Santa Sofia, 78, Catania, 95125, Italy
                Department of Neurology IC, Oasi Research Institute – IRCCS, Troina, Italy
                Department of Surgery and Medical-Surgery Specialties, University of Catania, Catania, Italy
                Department of Surgery and Medical-Surgery Specialties, University of Catania, Catania, Italy
                Department of Medical and Surgical Sciences and Advanced Technologies, Section of Neurosciences, University of Catania, Catania, Italy
                Department of Clinical Neurophysiology, University Medical Center, Georg August University, Göttingen, Germany
                Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
                Author notes
                Article
                10.1177_1756286419878317
                10.1177/1756286419878317
                6763938
                © The Author(s), 2019

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

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                Custom metadata
                January-December 2019

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