The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform
Walter Paulus - One of the best experts on this subject based on the ideXlab platform.
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dopaminergic modulation of long lasting direct current induced cortical Excitability changes in the human motor cortex
European Journal of Neuroscience, 2006Co-Authors: Michael A Nitsche, David Liebetanz, Nicolas Lang, Frithjof Tergau, Christian Lampe, Andrea Antal, Walter PaulusAbstract:Dopaminergic mechanisms participate in N-methyl-D-aspartate (NMDA) receptor-dependent neuroplasticity, as animal experiments have shown. This may be similar in humans, where dopamine influences learning and memory. We tested the role of dopamine in human cortical neuroplasticity. Changes of Excitability were induced by transcranial direct current stimulation (tDCS). D2 receptor blocking by sulpiride abolished the induction of after-effects nearly completely. D1 activation alone in the presence of D2 receptor blocking induced by co-administration of sulpiride and pergolide did not re-establish the Excitability changes induced by tDCS. This suggests that D2 receptors play a major supporting role in inducing neuroplasticity in the human motor cortex. Enhancement of D2 and, to a lesser degree, D1 receptors by pergolide consolidated tDCS-generated Excitability diminution until the morning after stimulation. The readiest explanation for this pattern of results is that D2 receptor activation has a consolidation-enhancing effect on tDCS-induced changes of Excitability in the human cortex. The results of this study underscore the importance of the dopaminergic system for human neuroplasticity, suggest a first pharmacological add-on mechanism to prolong the Excitability-diminishing effects of cathodal tDCS for up to 24 h after stimulation, and thus render the application of tDCS practicable in diseases displaying enhanced cortical Excitability, e.g. migraine and epilepsy.
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catecholaminergic consolidation of motor cortical neuroplasticity in humans
Cerebral Cortex, 2004Co-Authors: Michael A Nitsche, David Liebetanz, Nicolas Lang, Frithjof Tergau, Jessica Grundey, Walter PaulusAbstract:Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptordependent long-lasting Excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting Excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of Excitability which lasted until the morning after tDCS, compared to ∼1 h in the placebo condition. Prolongation of the Excitability enhancement was most pronounced for long-term effects; the duration of short-term Excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCSdriven Excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a β-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical Excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purposedesigned pharmacological interventions.
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gabaergic modulation of dc stimulation induced motor cortex Excitability shifts in humans
European Journal of Neuroscience, 2004Co-Authors: Michael A Nitsche, David Liebetanz, Anett Schlitterlau, Undine Henschke, K Fricke, Kai Frommann, Nicolas Lang, Stefan Henning, Walter Paulus, Frithjof TergauAbstract:Weak transcranial DC stimulation (tDCS) of the human motor cortex results in Excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances Excitability, whereas cathodal stimulation reduces it. Although the after-effects of tDCS are NMDA receptor-dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS. Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS-induced Excitability elevation. The initial absence of an Excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late-occurring Excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values, Excitability changes originating from remote cortical or subcortical areas could be involved.
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preconditioning of low frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation evidence for homeostatic plasticity in the human motor cortex
The Journal of Neuroscience, 2004Co-Authors: Hartwig R Siebner, Michael A Nitsche, Nicolas Lang, Walter Paulus, Vincenzo Rizzo, Roger N Lemon, John C RothwellAbstract:Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the Excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal Excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal Excitability for at least 20 min. No changes in Excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal Excitability within a physiologically useful range.
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pharmacological modulation of cortical Excitability shifts induced by transcranial direct current stimulation in humans
The Journal of Physiology, 2003Co-Authors: Michael A Nitsche, David Liebetanz, Anett Schlitterlau, Undine Henschke, K Fricke, Nicolas Lang, Stefan Henning, Frithjof Tergau, Walter PaulusAbstract:Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical Excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces Excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical Excitability changes of healthy human subjects were tested. tDCS-protocols inducing Excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the Excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated Excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical Excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven Excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.
Michael A Nitsche - One of the best experts on this subject based on the ideXlab platform.
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dopaminergic modulation of long lasting direct current induced cortical Excitability changes in the human motor cortex
European Journal of Neuroscience, 2006Co-Authors: Michael A Nitsche, David Liebetanz, Nicolas Lang, Frithjof Tergau, Christian Lampe, Andrea Antal, Walter PaulusAbstract:Dopaminergic mechanisms participate in N-methyl-D-aspartate (NMDA) receptor-dependent neuroplasticity, as animal experiments have shown. This may be similar in humans, where dopamine influences learning and memory. We tested the role of dopamine in human cortical neuroplasticity. Changes of Excitability were induced by transcranial direct current stimulation (tDCS). D2 receptor blocking by sulpiride abolished the induction of after-effects nearly completely. D1 activation alone in the presence of D2 receptor blocking induced by co-administration of sulpiride and pergolide did not re-establish the Excitability changes induced by tDCS. This suggests that D2 receptors play a major supporting role in inducing neuroplasticity in the human motor cortex. Enhancement of D2 and, to a lesser degree, D1 receptors by pergolide consolidated tDCS-generated Excitability diminution until the morning after stimulation. The readiest explanation for this pattern of results is that D2 receptor activation has a consolidation-enhancing effect on tDCS-induced changes of Excitability in the human cortex. The results of this study underscore the importance of the dopaminergic system for human neuroplasticity, suggest a first pharmacological add-on mechanism to prolong the Excitability-diminishing effects of cathodal tDCS for up to 24 h after stimulation, and thus render the application of tDCS practicable in diseases displaying enhanced cortical Excitability, e.g. migraine and epilepsy.
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catecholaminergic consolidation of motor cortical neuroplasticity in humans
Cerebral Cortex, 2004Co-Authors: Michael A Nitsche, David Liebetanz, Nicolas Lang, Frithjof Tergau, Jessica Grundey, Walter PaulusAbstract:Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptordependent long-lasting Excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting Excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of Excitability which lasted until the morning after tDCS, compared to ∼1 h in the placebo condition. Prolongation of the Excitability enhancement was most pronounced for long-term effects; the duration of short-term Excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCSdriven Excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a β-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical Excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purposedesigned pharmacological interventions.
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gabaergic modulation of dc stimulation induced motor cortex Excitability shifts in humans
European Journal of Neuroscience, 2004Co-Authors: Michael A Nitsche, David Liebetanz, Anett Schlitterlau, Undine Henschke, K Fricke, Kai Frommann, Nicolas Lang, Stefan Henning, Walter Paulus, Frithjof TergauAbstract:Weak transcranial DC stimulation (tDCS) of the human motor cortex results in Excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances Excitability, whereas cathodal stimulation reduces it. Although the after-effects of tDCS are NMDA receptor-dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS. Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS-induced Excitability elevation. The initial absence of an Excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late-occurring Excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values, Excitability changes originating from remote cortical or subcortical areas could be involved.
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preconditioning of low frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation evidence for homeostatic plasticity in the human motor cortex
The Journal of Neuroscience, 2004Co-Authors: Hartwig R Siebner, Michael A Nitsche, Nicolas Lang, Walter Paulus, Vincenzo Rizzo, Roger N Lemon, John C RothwellAbstract:Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the Excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal Excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal Excitability for at least 20 min. No changes in Excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal Excitability within a physiologically useful range.
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pharmacological modulation of cortical Excitability shifts induced by transcranial direct current stimulation in humans
The Journal of Physiology, 2003Co-Authors: Michael A Nitsche, David Liebetanz, Anett Schlitterlau, Undine Henschke, K Fricke, Nicolas Lang, Stefan Henning, Frithjof Tergau, Walter PaulusAbstract:Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical Excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces Excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical Excitability changes of healthy human subjects were tested. tDCS-protocols inducing Excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the Excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated Excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical Excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven Excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.
Robert Chen - One of the best experts on this subject based on the ideXlab platform.
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studies of human motor physiology with transcranial magnetic stimulation
Muscle & Nerve, 2000Co-Authors: Robert ChenAbstract:Transcranial magnetic stimulation (TMS) is a safe, noninvasive, and painless way to stimulate the human motor cortex in behaving human subjects. When it is applied as a single-pulse, measurements such as central conduction time, motor threshold, silent-period duration, recruitment curve, and mapping of muscle representation can be determined. Paired-pulse TMS is a useful way to examine cortical Excitability. Single and paired-pulse TMS have been applied to study plasticity following amputation and cortical Excitability in patients with dystonia. Another form of TMS is repetitive TMS (rTMS), with stimuli delivered repeatedly to a single scalp site. High-frequency rTMS can be used to transiently inactivate different cortical areas to study their functions. rTMS can also modulate cortical Excitability. At stimulus frequencies higher than 5 Hz, rTMS increases cortical Excitability, and stimulation around 1 Hz reduces cortical Excitability. Modulation of cortical Excitability by rTMS has therapeutic potential in psychiatric and neurological disorders. © 2000 John Wiley & Sons, Inc. Muscle Nerve Supplement 9:S26–S32, 2000.
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Effects of phenytoin on cortical Excitability in humans
Neurology, 1997Co-Authors: Robert Chen, Ali Samii, Michael Canos, Eric M. Wassermann, Mark HallettAbstract:We studied the effects of a loading dose of phenytoin on motor cortex Excitability in five healthy volunteers. Phenytoin elevated motor thresholds to transcranial magnetic stimulation (TMS) in all subjects, but had no effects on motor-evoked potential amplitudes, silent period durations, and intracortical Excitability tested by paired TMS during rest and voluntary muscle activation. These results are consistent with the hypothesis that blockade of voltage-gated sodium channels decreases membrane Excitability and elevates the threshold to TMS, but will not reduce intracortical Excitability.
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depression of motor cortex Excitability by low frequency transcranial magnetic stimulation
Neurology, 1997Co-Authors: Robert Chen, Eric M. Wassermann, Mark Hallett, Joseph Classen, Christian Gerloff, Pablo Celnik, Leonardo G CohenAbstract:We studied the effects of low-frequency transcranial magnetic stimulation (TMS) on motor cortex Excitability in humans. TMS at 0.1 Hz for 1 hour did not change cortical Excitability. Stimulation at 0.9 Hz for 15 minutes (810 pulses), similar to the parameters used to induce long-term depression (LTD) in cortical slice preparations and in vivo animal studies, led to a mean decrease in motor evoked potential (MEP) amplitude of 19.5%. The decrease in cortical Excitability lasted for at least 15 minutes after the end of the 0.9 Hz stimulation. The mechanism underlying this decrease in Excitability may be similar to LTD. TMS-induced reduction of cortical Excitability has potential clinical applications in diseases such as epilepsy and myoclonus. Spread of excitation, which may be a warning sign for seizures, occurred in one subject and was not accompanied by increased MEP amplitude, suggesting that spread of excitation and amplitude changes are different phenomena and also indicating the need for adequate monitoring even with stimulations at low frequencies.
Nicolas Lang - One of the best experts on this subject based on the ideXlab platform.
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dopaminergic modulation of long lasting direct current induced cortical Excitability changes in the human motor cortex
European Journal of Neuroscience, 2006Co-Authors: Michael A Nitsche, David Liebetanz, Nicolas Lang, Frithjof Tergau, Christian Lampe, Andrea Antal, Walter PaulusAbstract:Dopaminergic mechanisms participate in N-methyl-D-aspartate (NMDA) receptor-dependent neuroplasticity, as animal experiments have shown. This may be similar in humans, where dopamine influences learning and memory. We tested the role of dopamine in human cortical neuroplasticity. Changes of Excitability were induced by transcranial direct current stimulation (tDCS). D2 receptor blocking by sulpiride abolished the induction of after-effects nearly completely. D1 activation alone in the presence of D2 receptor blocking induced by co-administration of sulpiride and pergolide did not re-establish the Excitability changes induced by tDCS. This suggests that D2 receptors play a major supporting role in inducing neuroplasticity in the human motor cortex. Enhancement of D2 and, to a lesser degree, D1 receptors by pergolide consolidated tDCS-generated Excitability diminution until the morning after stimulation. The readiest explanation for this pattern of results is that D2 receptor activation has a consolidation-enhancing effect on tDCS-induced changes of Excitability in the human cortex. The results of this study underscore the importance of the dopaminergic system for human neuroplasticity, suggest a first pharmacological add-on mechanism to prolong the Excitability-diminishing effects of cathodal tDCS for up to 24 h after stimulation, and thus render the application of tDCS practicable in diseases displaying enhanced cortical Excitability, e.g. migraine and epilepsy.
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catecholaminergic consolidation of motor cortical neuroplasticity in humans
Cerebral Cortex, 2004Co-Authors: Michael A Nitsche, David Liebetanz, Nicolas Lang, Frithjof Tergau, Jessica Grundey, Walter PaulusAbstract:Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptordependent long-lasting Excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting Excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of Excitability which lasted until the morning after tDCS, compared to ∼1 h in the placebo condition. Prolongation of the Excitability enhancement was most pronounced for long-term effects; the duration of short-term Excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCSdriven Excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a β-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical Excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purposedesigned pharmacological interventions.
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gabaergic modulation of dc stimulation induced motor cortex Excitability shifts in humans
European Journal of Neuroscience, 2004Co-Authors: Michael A Nitsche, David Liebetanz, Anett Schlitterlau, Undine Henschke, K Fricke, Kai Frommann, Nicolas Lang, Stefan Henning, Walter Paulus, Frithjof TergauAbstract:Weak transcranial DC stimulation (tDCS) of the human motor cortex results in Excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances Excitability, whereas cathodal stimulation reduces it. Although the after-effects of tDCS are NMDA receptor-dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS. Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS-induced Excitability elevation. The initial absence of an Excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late-occurring Excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values, Excitability changes originating from remote cortical or subcortical areas could be involved.
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preconditioning of low frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation evidence for homeostatic plasticity in the human motor cortex
The Journal of Neuroscience, 2004Co-Authors: Hartwig R Siebner, Michael A Nitsche, Nicolas Lang, Walter Paulus, Vincenzo Rizzo, Roger N Lemon, John C RothwellAbstract:Recent experimental work in animals has emphasized the importance of homeostatic plasticity as a means of stabilizing the properties of neuronal circuits. Here, we report a phenomenon that indicates a homeostatic pattern of cortical plasticity in healthy human subjects. The experiments combined two techniques that can produce long-term effects on the Excitability of corticospinal output neurons: transcranial direct current stimulation (TDCS) and repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex. "Facilitatory preconditioning" with anodal TDCS caused a subsequent period of 1 Hz rTMS to reduce corticospinal Excitability to below baseline levels for >20 min. Conversely, "inhibitory preconditioning" with cathodal TDCS resulted in 1 Hz rTMS increasing corticospinal Excitability for at least 20 min. No changes in Excitability occurred when 1 Hz rTMS was preceded by sham TDCS. Thus, changing the initial state of the motor cortex by a period of DC polarization reversed the conditioning effects of 1 Hz rTMS. These preconditioning effects of TDCS suggest the existence of a homeostatic mechanism in the human motor cortex that stabilizes corticospinal Excitability within a physiologically useful range.
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pharmacological modulation of cortical Excitability shifts induced by transcranial direct current stimulation in humans
The Journal of Physiology, 2003Co-Authors: Michael A Nitsche, David Liebetanz, Anett Schlitterlau, Undine Henschke, K Fricke, Nicolas Lang, Stefan Henning, Frithjof Tergau, Walter PaulusAbstract:Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical Excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces Excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical Excitability changes of healthy human subjects were tested. tDCS-protocols inducing Excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the Excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated Excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical Excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven Excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.
Frithjof Tergau - One of the best experts on this subject based on the ideXlab platform.
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dopaminergic modulation of long lasting direct current induced cortical Excitability changes in the human motor cortex
European Journal of Neuroscience, 2006Co-Authors: Michael A Nitsche, David Liebetanz, Nicolas Lang, Frithjof Tergau, Christian Lampe, Andrea Antal, Walter PaulusAbstract:Dopaminergic mechanisms participate in N-methyl-D-aspartate (NMDA) receptor-dependent neuroplasticity, as animal experiments have shown. This may be similar in humans, where dopamine influences learning and memory. We tested the role of dopamine in human cortical neuroplasticity. Changes of Excitability were induced by transcranial direct current stimulation (tDCS). D2 receptor blocking by sulpiride abolished the induction of after-effects nearly completely. D1 activation alone in the presence of D2 receptor blocking induced by co-administration of sulpiride and pergolide did not re-establish the Excitability changes induced by tDCS. This suggests that D2 receptors play a major supporting role in inducing neuroplasticity in the human motor cortex. Enhancement of D2 and, to a lesser degree, D1 receptors by pergolide consolidated tDCS-generated Excitability diminution until the morning after stimulation. The readiest explanation for this pattern of results is that D2 receptor activation has a consolidation-enhancing effect on tDCS-induced changes of Excitability in the human cortex. The results of this study underscore the importance of the dopaminergic system for human neuroplasticity, suggest a first pharmacological add-on mechanism to prolong the Excitability-diminishing effects of cathodal tDCS for up to 24 h after stimulation, and thus render the application of tDCS practicable in diseases displaying enhanced cortical Excitability, e.g. migraine and epilepsy.
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catecholaminergic consolidation of motor cortical neuroplasticity in humans
Cerebral Cortex, 2004Co-Authors: Michael A Nitsche, David Liebetanz, Nicolas Lang, Frithjof Tergau, Jessica Grundey, Walter PaulusAbstract:Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptordependent long-lasting Excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting Excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of Excitability which lasted until the morning after tDCS, compared to ∼1 h in the placebo condition. Prolongation of the Excitability enhancement was most pronounced for long-term effects; the duration of short-term Excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCSdriven Excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a β-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical Excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purposedesigned pharmacological interventions.
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gabaergic modulation of dc stimulation induced motor cortex Excitability shifts in humans
European Journal of Neuroscience, 2004Co-Authors: Michael A Nitsche, David Liebetanz, Anett Schlitterlau, Undine Henschke, K Fricke, Kai Frommann, Nicolas Lang, Stefan Henning, Walter Paulus, Frithjof TergauAbstract:Weak transcranial DC stimulation (tDCS) of the human motor cortex results in Excitability shifts during and after the end of stimulation, which are most probably localized intracortically. Anodal stimulation enhances Excitability, whereas cathodal stimulation reduces it. Although the after-effects of tDCS are NMDA receptor-dependent, nothing is known about the involvement of additional receptors. Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS. Administration of the GABA(A) receptor agonist lorazepam resulted in a delayed, but then enhanced and prolonged anodal tDCS-induced Excitability elevation. The initial absence of an Excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation, which occurs without pharmacological intervention. The reasons for the late-occurring Excitability enhancement remain unclear. Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values, Excitability changes originating from remote cortical or subcortical areas could be involved.
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pharmacological modulation of cortical Excitability shifts induced by transcranial direct current stimulation in humans
The Journal of Physiology, 2003Co-Authors: Michael A Nitsche, David Liebetanz, Anett Schlitterlau, Undine Henschke, K Fricke, Nicolas Lang, Stefan Henning, Frithjof Tergau, Walter PaulusAbstract:Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarity-specific shifts of cortical Excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces Excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical Excitability changes of healthy human subjects were tested. tDCS-protocols inducing Excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the Excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated Excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical Excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven Excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications.
