GABAergic modulation of DC stimulation‐induced motor cortex excitability shifts in humans

Nitsche, Michael A.; Liebetanz, David; Schlitterlau, Anett; Henschke, Undine; Fricke, K.; Frommann, Kai; Lang, N.; Henning, Stephan; Paulus, Walter; Tergau, Frithjof

doi:10.1111/j.0953-816x.2004.03398.x

Cited by 323 publications

(241 citation statements)

References 19 publications

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“…Accordingly, activation of 5-HT2 receptors has a facilitatory effect on NMDA receptor-dependent LTP induction in the visual cortex of adult rats (Park et al, 2012). Finally, serotonin affects cholinergic (Consolo et al, 1994;Matsumoto et al, 2001;Yamaguchi et al, 1997), GABAergic (Roerig and Katz, 1997;Waider et al, 2012), nicotinergic (Zaniewska et al, 2009), and dopaminergic (Gobert and Millan, 1999;Wood and Wren, 2008) systems, which have a major impact on stimulation-induced plasticity in humans Kuo et al, 2008;Monte-Silva et al, 2009;Monte-Silva et al, 2010;Nitsche et al, 2004;Thirugnanasambandam et al, 2012). While it cannot be ruled out completely that serotonin enhancement affected plasticity partially by its impact on one of these neuromodulatory systems, a profound contribution seems unlikely, because the impact of citalopram on tDCS-, and PAS-induced plasticity differs relevantly from those of other neuromodulators.…”

Section: Proposed Mechanisms Of Actionmentioning

confidence: 99%

Effect of Serotonin on Paired Associative Stimulation-Induced Plasticity in the Human Motor Cortex

Batsikadze

Paulus

Kuo

et al. 2013

Neuropsychopharmacol

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Serotonin modulates diverse brain functions. Beyond its clinical antidepressant effects, it improves motor performance, learning and memory formation. These effects might at least be partially caused by the impact of serotonin on neuroplasticity, which is thought to be an important foundation of the respective functions. In principal accordance, selective serotonin reuptake inhibitors enhance long-term potentiation-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. As other neuromodulators have discernable effects on different kinds of plasticity in humans, here we were interested to explore the impact of serotonin on paired associative stimulation (PAS)-induced plasticity, which induces a more focal kind of plasticity, as compared with tDCS, shares some features with spike timing-dependent plasticity, and is thought to be relative closely related to learning processes. In this single-blinded, placebo-controlled, randomized crossover study, we administered a single dose of 20 mg citalopram or placebo medication and applied facilitatory-and excitability-diminishing PAS to the left motor cortex of 14 healthy subjects. Cortico-spinal excitability was explored via single-pulse transcranial magnetic stimulation-elicited MEP amplitudes up to the next evening after plasticity induction. After citalopram administration, inhibitory PAS-induced after-effects were abolished and excitatory PAS-induced after-effects were enhanced trendwise, as compared with the respective placebo conditions. These results show that serotonin modulates PAS-induced neuroplasticity by shifting it into the direction of facilitation, which might help to explain mechanism of positive therapeutic effects of serotonin in learning and medical conditions characterized by enhanced inhibitory or reduced facilitatory plasticity, including depression and stroke.

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Section: Proposed Mechanisms Of Actionmentioning

confidence: 99%

Effect of Serotonin on Paired Associative Stimulation-Induced Plasticity in the Human Motor Cortex

Batsikadze

Paulus

Kuo

et al. 2013

Neuropsychopharmacol

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“…Within the cortex, tDCS modulates synaptic strength and likely stimulates neurons in the cortex, pyramidal neurons, and interneurons (Stagg and Nitsche, 2011). Several neuromodulators such as GABA (Stagg et al, 2009), Na + and Ca 2+ channel blockers (Nitsche et al, 2004), l-DOPA (Kuo et al, 2008), and the D 2 receptor agonists Monte-Silva et al, 2009) also have an effect on increasing and/or decreasing the effects of tDCS stimulation (for more see Stagg and Nitsche, 2011). Some progress in linking DNA genotypes with cognitive performance is underway.…”

Section: Mechanisms Of Tdcsmentioning

confidence: 99%

Parietal Contributions to Visual Working Memory Depend on Task Difficulty

Jones¹,

Crane²,

Feenstra³

et al. 2012

PsycEXTRA Dataset

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The nature of parietal contributions to working memory (WM) remain poorly understood but of considerable interest. We previously reported that posterior parietal damage selectively impaired WM probed by recognition (Berryhill and Olson, 2008a). Recent studies provided support using a neuromodulatory technique, transcranial direct current stimulation (tDCS) applied to the right parietal cortex (P4). These studies confirmed parietal involvement in WM because parietal tDCS altered WM performance: anodal current tDCS improved performance in a change detection task, and cathodal current tDCS impaired performance on a sequential presentation task. Here, we tested whether these complementary results were due to different degrees of parietal involvement as a function of WM task demands, WM task difficulty, and/or participants' WM capacity. In Experiment 1, we applied cathodal and anodal tDCS to the right parietal cortex and tested participants on both previously used WM tasks. We observed an interaction between tDCS (anodal, cathodal), WM task difficulty, and participants' WM capacity. When the WM task was difficult, parietal stimulation (anodal or cathodal) improved WM performance selectively in participants with high WM capacity. In the low WM capacity group, parietal stimulation (anodal or cathodal) impaired WM performance. These nearly equal and opposite effects were only observed when the WM task was challenging, as in the change detection task. Experiment 2 probed the interplay of WM task difficulty and WM capacity in a parametric manner by varying set size in the WM change detection task. Here, the effect of parietal stimulation (anodal or cathodal) on the high WM capacity group followed a linear function as WM task difficulty increased with set size. The low WM capacity participants were largely unaffected by tDCS. These findings provide evidence that parietal involvement in WM performance depends on both WM capacity and WM task demands. We discuss these findings in terms of alternative WM strategies employed by low and high WM capacity individuals. We speculate that low WM capacity individuals do not recruit the posterior parietal lobe for WM tasks as efficiently as high WM capacity individuals. Consequently, tDCS provides greater benefit to individuals with high WM capacity.

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“…In contrast, cathodal tDCS decreases cortical excitability, shifting the resting membrane potential towards hyperpolarization and reducing the firing rate of neurons (Bindman et al, 1964a;Creutzfeldt et al, 1962;Purpura and McMurtry, 1965). The involvement of mechanisms similar to those underlying long-term potentiation (LTP) and long-term depression (LTD) was hypothesized to explain the tDCS induced neuroplasticity after-effects (Liebetanz et al, 2002;Nitsche et al, 2003b;Nitsche et al, 2004). The changes in neurophysiologic excitability induced by tDCS over the human primary motor cortex (M1) and their underlying mechanisms have been indirectly inferred by assessing the modifications in the excitability of the corticospinal tract using transcranial magnetic stimulation (TMS) protocols (Lang et al, 2011;Nitsche and Paulus, 2000;Nitsche and Paulus, 2001;Nitsche et al, 2005;Priori et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Excitability modulation of the motor system induced by transcranial direct current stimulation: A multimodal approach

2013

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Anodal and cathodal transcranial direct current stimulations (tDCS) are both established techniques to induce cortical excitability changes. Typically, in the human motor system, such cortical modulations are inferred through changes in the amplitude of the motor evoked potentials (MEPs). However, it is now possible to directly evaluate tDCS-induced changes at the cortical level by recording the transcranial magnetic stimulation evoked potentials (TEPs) using electroencephalography (EEG). The present study investigated the modulation induced by the tDCS on the motor system. The study evaluates changes in the MEPs, in the amplitude and distribution of the TEPs, in resting state oscillatory brain activity and in behavioral performance in a simple manual response task. Both the short-and long-term tDCS effects were investigated by evaluating their time course at~0 and 30 min after tDCS. Anodal tDCS over the left primary motor cortex (M1) induced an enhancement of corticospinal excitability, whereas cathodal stimulation produced a reduction. These changes in excitability were indexed by changes in MEP amplitude. More interestingly, tDCS modulated the cortical reactivity, which is the neuronal activity evoked by TMS, in a polarity-dependent and site-specific manner. Cortical reactivity increased after anodal stimulation over the left M1, whereas it decreased with cathodal stimulation. These effects were partially present also at long term evaluation. No polarity-specific effect was found either on behavioral measures or on oscillatory brain activity. The latter showed a general increase in the power density of low frequency oscillations (theta and alpha) at both stimulation polarities. Our results suggest that tDCS is able to modulate motor cortical reactivity in a polarity-specific manner, inducing a complex pattern of direct and indirect cortical activations or inhibitions of the motor system-related network, which might be related to changes in synaptic efficacy of the motor cortex.

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GABAergic modulation of DC stimulation‐induced motor cortex excitability shifts in humans

Cited by 323 publications

References 19 publications

Effect of Serotonin on Paired Associative Stimulation-Induced Plasticity in the Human Motor Cortex

Effect of Serotonin on Paired Associative Stimulation-Induced Plasticity in the Human Motor Cortex

Parietal Contributions to Visual Working Memory Depend on Task Difficulty

Excitability modulation of the motor system induced by transcranial direct current stimulation: A multimodal approach

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