Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation.
TL;DR: Repeated tDCS within a specific time window is able to induce l-LTP-like plasticity in the human motor cortex.
About: This article is published in Brain Stimulation.The article was published on 2013-05-01. It has received 649 citations till now. The article focuses on the topics: Brain stimulation & Transcranial direct-current stimulation.
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Paris 12 Val de Marne University1, University of Göttingen2, University Hospital of Lausanne3, French Institute of Health and Medical Research4, University of Milan5, University of Otago6, University of Regensburg7, University of Marburg8, Ruhr University Bochum9, Ludwig Maximilian University of Munich10, University of Siena11, University of Texas at Dallas12, University of Tübingen13
TL;DR: It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting.
1,062 citations
Cites background from "Induction of late LTP-like plastici..."
...One should also consider the major influence of stimulation parameters, such as intensity (Batsikadze et al., 2013) and session repetition timing (Monte-Silva et al., 2010a, 2013), which reflect some aspects of the non-linear relationship between tDCS settings and the biological effects produced....
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University of Florida1, University of Göttingen2, City College of New York3, Mackenzie Presbyterian University4, University of São Paulo5, Johns Hopkins University6, National Institutes of Health7, Harvard University8, University of California, Davis9, University of Brescia10, University of Lisbon11, University of Oxford12, ETH Zurich13, Ruhr University Bochum14
TL;DR: This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches to help the reader to appropriately design and conduct studies involving these brain stimulation techniques.
942 citations
Cites background or methods from "Induction of late LTP-like plastici..."
...In this section we will describe the two most common electrode montages utilized in different laboratories (for a detailed review on the technique and cerebellar tDCS applications see Ferrucci and Priori, 2014a; Grimaldi et al., 2014; Priori et al., 2014)....
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...Further extension of stimulation duration and/or intensity will not necessarily result in a relative increase, but can invert stimulation effects (Batsikadze et al., 2013; Monte-Silva et al., 2013b)....
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...For the induction of relevantly longer-lasting tDCS effects, spaced stimulation with intervals 630 min is suited (Monte-Silva et al., 2013b; Goldsworthy et al., 2014)....
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...For long-term plasticity effects, an interval of one week should avoid interferences, whereas a 24 h break is insufficient (Monte-Silva et al., 2010, 2013a)....
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...For (d), post-intervention TMS has been performed for up to over 24 h (Monte-Silva et al., 2010, 2013a)....
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City College of New York1, Mackenzie Presbyterian University2, University of São Paulo3, New York University4, Beth Israel Deaconess Medical Center5, University Medical Center Freiburg6, University of Minnesota7, University of Pennsylvania8, University of Michigan9, Air Force Research Laboratory10, University of Calgary11, Albert Einstein College of Medicine12, University of Göttingen13, University of New South Wales14, University of Freiburg15, University of South Carolina16, MedStar National Rehabilitation Hospital17, University of Florida18
TL;DR: Evidence from relevant animal models indicates that brain injury by Direct Current Stimulation (DCS) occurs at predicted brain current densities that are over an order of magnitude above those produced by conventional tDCS.
874 citations
Cites background from "Induction of late LTP-like plastici..."
...[174], including when paired with a behavioral program to enhance outcome (e....
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TL;DR: I‐waves, input–output curves and cortical silent period are unaffected immediately after 2 mA stimulation and short intracortical inhibition and facilitation are shifted towards excitability enhancement after both anodal and cathodal stimulation.
Abstract: Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2) has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition. No significant changes were observed in the other protocols. Sham tDCS did not induce significant MEP alterations. These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation, but might also shift the direction of excitability alterations. This should be taken into account for applications of the stimulation technique using different intensities and durations in order to achieve stronger or longer lasting after-effects.
814 citations
TL;DR: The state of non-invasive brain stimulation research in humans is summarized, some current debates about properties and limitations of these methods are discussed, and recommendations for how these challenges may be addressed are given.
Abstract: In the past three decades, our understanding of brain–behavior relationships has been significantly shaped by research using non-invasive brain stimulation (NIBS) techniques. These methods allow non-invasive and safe modulation of neural processes in the healthy brain, enabling researchers to directly study how experimentally altered neural activity causally affects behavior. This unique property of NIBS methods has, on the one hand, led to groundbreaking findings on the brain basis of various aspects of behavior and has raised interest in possible clinical and practical applications of these methods. On the other hand, it has also triggered increasingly critical debates about the properties and possible limitations of these methods. In this review, we discuss these issues, clarify the challenges associated with the use of currently available NIBS techniques for basic research and practical applications, and provide recommendations for studies using NIBS techniques to establish brain–behavior relationships.
544 citations
References
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TL;DR: This work reviews those forms of LTP and LTD for which mechanisms have been most firmly established and examples are provided that show how these mechanisms can contribute to experience-dependent modifications of brain function.
3,767 citations
TL;DR: The investigation of how the CNS learns to control movements in different dynamical conditions, and how this learned behavior is represented, suggests that the elements of the adaptive process represent dynamics of a motor task in terms of the intrinsic coordinate system of the sensors and actuators.
Abstract: We investigated how the CNS learns to control movements in different dynamical conditions, and how this learned behavior is represented. In particular, we considered the task of making reaching movements in the presence of externally imposed forces from a mechanical environment. This environment was a force field produced by a robot manipulandum, and the subjects made reaching movements while holding the end-effector of this manipulandum. Since the force field significantly changed the dynamics of the task, subjects' initial movements in the force field were grossly distorted compared to their movements in free space. However, with practice, hand trajectories in the force field converged to a path very similar to that observed in free space. This indicated that for reaching movements, there was a kinematic plan independent of dynamical conditions. The recovery of performance within the changed mechanical environment is motor adaptation. In order to investigate the mechanism underlying this adaptation, we considered the response to the sudden removal of the field after a training phase. The resulting trajectories, named aftereffects, were approximately mirror images of those that were observed when the subjects were initially exposed to the field. This suggested that the motor controller was gradually composing a model of the force field, a model that the nervous system used to predict and compensate for the forces imposed by the environment. In order to explore the structure of the model, we investigated whether adaptation to a force field, as presented in a small region, led to aftereffects in other regions of the workspace. We found that indeed there were aftereffects in workspace regions where no exposure to the field had taken place; that is, there was transfer beyond the boundary of the training data. This observation rules out the hypothesis that the subject's model of the force field was constructed as a narrow association between visited states and experienced forces; that is, adaptation was not via composition of a look-up table. In contrast, subjects modeled the force field by a combination of computational elements whose output was broadly tuned across the motor state space. These elements formed a model that extrapolated to outside the training region in a coordinate system similar to that of the joints and muscles rather than end-point forces. This geometric property suggests that the elements of the adaptive process represent dynamics of a motor task in terms of the intrinsic coordinate system of the sensors and actuators.
2,505 citations
TL;DR: The authors show that in the human transcranial direct current stimulation is able to induce sustained cortical excitability elevations, and this technique is a potentially valuable tool in neuroplasticity modulation.
Abstract: The authors show that in the human transcranial direct current stimulation is able to induce sustained cortical excitability elevations. As revealed by transcranial magnetic stimulation, motor cortical excitability increased approximately 150% above baseline for up to 90 minutes after the end of stimulation. The feasibility of inducing long-lasting excitability modulations in a noninvasive, painless, and reversible way makes this technique a potentially valuable tool in neuroplasticity modulation.
2,289 citations
TL;DR: A slowly evolving, long-term, experience-dependent reorganization of the adult Ml is suggested, which may underlie the acquisition and retention of the motor skill.
Abstract: Performance of complex motor tasks, such as rapid sequences of finger movements, can be improved in terms of speed and accuracy over several weeks by daily practice sessions. This improvement does not generalize to a matched sequence of identical component movements, nor to the contralateral hand. Here we report a study of the neural changes underlying this learning using functional magnetic resonance imaging (MRI) of local blood oxygenation level-dependent (BOLD) signals evoked in primary motor cortex (M1). Before training, a comparable extent of M1 was activated by both sequences. However, two ordering effects were observed: repeating a sequence within a brief time window initially resulted in a smaller area of activation (habituation), but later in larger area of activation (enhancement), suggesting a switch in M1 processing mode within the first session (fast learning). By week 4 of training, concurrent with asymptotic performance, the extent of cortex activated by the practised sequence enlarged compared with the unpractised sequence, irrespective of order (slow learning). These changes persisted for several months. The results suggest a slowly evolving, long-term, experience-dependent reorganization of the adult M1, which may underlie the acquisition and retention of the motor skill.
1,798 citations
TL;DR: Pentoxifylline offers a well-tolerated and effective alternative to the treatment options available for patients with peripheral vascular disease and in isolated studies proved to be superior to drugs such as co-dergocrine mesylate, adenosine and pyrithioxine.
Abstract: Pentoxifylline (oxpentifylline) is an orally active haemorheological agent for the treatment of peripheral vascular disease, cerebrovascular disease and a number of other conditions involving a defective regional microcirculation. Pentoxifylline acts primarily by increasing red blood cell deformability, by reducing blood viscosity and by decreasing the potential for platelet aggregation and thrombus formation. Extensive open and placebo-controlled studies have shown that pentoxifylline 600 to 1200 mg/day for at least 6 weeks is associated with subjective and objective improvements in 60 to 100% of patients with peripheral vascular disease. The most commonly assessed clinical parameter, walking distance, is usually improved by about 100%, although much greater improvements have also been documented. Other parameters which have been clearly improved include lower limb rest pain, paraesthesia, muscle blood flow, cramps and leg ulcers. Pentoxifylline has produced consistently better results than placebo, and in those studies using comparative drugs, better results than nylidrin, adenosine and naftidrofuryl. In patients with cerebrovascular disorders, open studies with pentoxifylline, usually at a dosage of 600 to 1200 mg/day (300 to 600 mg/day in Japan), have shown marked overall clinical improvements in about 85% of patients. Symptomatic improvements in rehabilitation psychometric tests, neuromotor and speech deficits and other subjective symptoms have accompanied increased cerebral blood flow, particularly to ischaemic areas. Pentoxifylline would appear to be useful in most types of cerebrovascular disease including transient ischaemic attacks, sequelae of cerebral thrombosis and haemorrhage, and chronic ischaemic disorders. In patients with chronic cerebrovascular disease pentoxifylline 600 to 1200 mg/day conferred significant clinical benefit compared with placebo and in isolated studies proved to be superior to drugs such as co-dergocrine mesylate, adenosine and pyrithioxine. Preliminary studies indicate that pentoxifylline may also prove useful in vaso-occlusive crises of sickle cell disease, some hearing disorders, disorders of eye circulation, high altitude sickness and asthenozoospermia. Pentoxifylline is usually well tolerated when administered as the conventional controlled release formulation, gastrointestinal symptoms (about 3%) being the most common complaint, although these and other adverse effects have not occurred to a significantly greater extent than with placebo. Thus, pentoxifylline offers a well-tolerated and effective alternative to the treatment options available for patients with peripheral vascular disease.(ABSTRACT TRUNCATED AT 400 WORDS)
1,788 citations