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Transcranial electrical stimulation - tDCS and friends MA Nitsche Georg-August-University, Dept. Clinical Neurophysiology, Goettingen, Germany
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Electrical Stimulation in the 18th century
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Electrical Stimulation in the 19th century
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(1910)
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Transcranial electrical stimulation (TES) 1980
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Common aspects of these treatments Suprathreshold stimulation Phenomenological effects DCS Subthreshold stimulation Physiological effects
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Principal action of DC-stimulation: modulation of resting membrane potential
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Text Cortical DC-stimulation of the rat: effects during stimulation … Bindman et al. 1964 Baseline cathodalanodal
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…and after-effects Bindman et al. 1964 cathodal anodal
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After-effects are protein synthesis- dependent Gartside 1968
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…and accompanied by specific biochemical alterations dark neurones3 h stimulation30 min
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50% of transcranially applied direct currents reach the brain - calculations on realistic head models, validation in animal experiments (Rush & Driscoll 1968) - validation in humans (Dymond et al. 1975)
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tDCS in humans
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Polarity-dependent excitability- modulation during tDCS Nitsche & Paulus 2000
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Enhanced motor cortico-spinal excitability after anodal stimulation Nitsche & Paulus 2001
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Reduced motor cortico-spinal excitability after cathodal tDCS 0.4 0.6 0.8 1.2 15101520253035404550556090120 min 1.0 Nitsche et al. 2003
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Mechanisms of action - the electrophysiological perspective DC electrode Pt-neuron Intracortical afferents
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Cortico-spinal effects DC electrode Pt-neuron Intracortical afferents I-O curve Intra-tDCS 0 10 20 30 40 50 60 70 non (a) non (c) anodal cathodal 1 mA, 35 cm 2 Resting motor thresholdActive motor threshold Nitsche et al. 2005
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Pt-neuron effects DC electrode Pt-neuron Intracortical afferents anodal cathodal Nitsche & Paulus 2000, 2001, Nitsche et al. 2003Ardolino et al. 2005 1 mA, 35 cm 2 1,5 mA, 35 cm 2 TMS TES
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intracortical effects DC electrode Pt-neuron Intracortical afferents intracortical facilitation/inhibition I-wave facilitation anodal cathodal 1 mA, 35 cm 2 anodal cathodal 1 mA, 35 cm 2 Nitsche et al. 2005
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Differentiation between intracortical/corticospinal effects DC electrode Pt- neuron Intracortical afferents DC electrode Pt- neuron Intracortical afferents Boros et al. 2008
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Conclusion I Cortico-spinal effects SP-MEP, I-O curve, (threshold) Intracortical effects SICI, ICF, (I-waves) Pt neurons (TES) ?????
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Mechanisms of action - pharmacological perspective Na, Ca NMDA GABA DA ACh Serotonin e Transmitter Mdodulator
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Acute effects of tDCS are ion channel- dependent Drug and stimulation condition Nitsche et al. 2003, 2004
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Pharmacological dependance of after-effects of tDCS I Nitsche et al. 2003
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Pharmacological dependance of after-effects of tDCS II Nitsche et al. 2003, 2004
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Pharmacological modulation of after-effects I Nitsche et al. 2006, Kuo et al. 2008
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Pharmacological modulation of after-effects II Kuo et al. 2008, 2007, Nitsche et al., 2009
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Conclusion II GLU NMDA Ca Na, Ca GABA DA ACh ??????? Serotonine Ca AMPA
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Focality of tDCS ImagingFunctional Baudewig et al. 2001, Lang et al. 2005 M1 premoto r Nitsche et al. 2005
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Increasing the focality of tDCS by reducing the size of the stimulation electrode I Nitsche et al. 2007
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Increasing the focality of tDCS by reducing the size of the stimulation electrode II
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Increasing the focality of tDCS by increasing the size of the reference electrode
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Safety of tDCS -No enhancement of NSE (Nitsche & Paulus 2001, Nitsche et al. 2003 -No cerebral edemas or related alterations (Nitsche et al. 2004) -No epileptic seizures (Liebetanz et al. 2006) -Current protocols well below the threshold of tissue damage (Liebetanz et al. 2009)
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Recent developments tACStRNS
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tACS Relatively small effects on motor cortex excitability... Antal et al. 2008
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...but prominent functional effects Antal et al. 2008, Kanai et al. 2008
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tRNS Terney et al. 2008 Motor cortex excitability Motor learning
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What to choose tDCS tACStRNS Current flowconstantsinusoidalrandom Mechanisms of actionStudies available?? SafetyStudies available?? ExcitabilityFacilitation/inhibitionFacilitation Spontaneous activityModulationSynchronisation?Desynchronisation? Learning+++ Clinical applicationStudies available??
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Thanks for your attention
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