Transcranial electrical stimulation - tDCS and friends MA Nitsche Georg-August-University, Dept. Clinical Neurophysiology, Goettingen, Germany

Electrical Stimulation in the 18th century

Electrical Stimulation in the 19th century

(1910)

Transcranial electrical stimulation (TES) 1980

Common aspects of these treatments Suprathreshold stimulation Phenomenological effects DCS Subthreshold stimulation Physiological effects

Principal action of DC-stimulation: modulation of resting membrane potential

Text Cortical DC-stimulation of the rat: effects during stimulation … Bindman et al Baseline cathodalanodal

…and after-effects Bindman et al cathodal anodal

After-effects are protein synthesis- dependent Gartside 1968

…and accompanied by specific biochemical alterations dark neurones3 h stimulation30 min

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)

tDCS in humans

Polarity-dependent excitability- modulation during tDCS Nitsche & Paulus 2000

Enhanced motor cortico-spinal excitability after anodal stimulation Nitsche & Paulus 2001

Reduced motor cortico-spinal excitability after cathodal tDCS min 1.0 Nitsche et al. 2003

Mechanisms of action - the electrophysiological perspective DC electrode Pt-neuron Intracortical afferents

Cortico-spinal effects DC electrode Pt-neuron Intracortical afferents I-O curve Intra-tDCS non (a) non (c) anodal cathodal 1 mA, 35 cm 2 Resting motor thresholdActive motor threshold Nitsche et al. 2005

Pt-neuron effects DC electrode Pt-neuron Intracortical afferents anodal cathodal Nitsche & Paulus 2000, 2001, Nitsche et al. 2003Ardolino et al mA, 35 cm 2 1,5 mA, 35 cm 2 TMS TES

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

Differentiation between intracortical/corticospinal effects DC electrode Pt- neuron Intracortical afferents DC electrode Pt- neuron Intracortical afferents Boros et al. 2008

Conclusion I Cortico-spinal effects SP-MEP, I-O curve, (threshold) Intracortical effects SICI, ICF, (I-waves) Pt neurons (TES) ?????

Mechanisms of action - pharmacological perspective Na, Ca NMDA GABA DA ACh Serotonin e Transmitter Mdodulator

Acute effects of tDCS are ion channel- dependent Drug and stimulation condition Nitsche et al. 2003, 2004

Pharmacological dependance of after-effects of tDCS I Nitsche et al. 2003

Pharmacological dependance of after-effects of tDCS II Nitsche et al. 2003, 2004

Pharmacological modulation of after-effects I Nitsche et al. 2006, Kuo et al. 2008

Pharmacological modulation of after-effects II Kuo et al. 2008, 2007, Nitsche et al., 2009

Conclusion II GLU NMDA Ca Na, Ca GABA DA ACh ??????? Serotonine Ca AMPA

Focality of tDCS ImagingFunctional Baudewig et al. 2001, Lang et al M1 premoto r Nitsche et al. 2005

Increasing the focality of tDCS by reducing the size of the stimulation electrode I Nitsche et al. 2007

Increasing the focality of tDCS by reducing the size of the stimulation electrode II

Increasing the focality of tDCS by increasing the size of the reference electrode

Safety of tDCS -No enhancement of NSE (Nitsche & Paulus 2001, Nitsche et al 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)

Recent developments tACStRNS

tACS Relatively small effects on motor cortex excitability... Antal et al. 2008

...but prominent functional effects Antal et al. 2008, Kanai et al. 2008

tRNS Terney et al Motor cortex excitability Motor learning

What to choose tDCS tACStRNS Current flowconstantsinusoidalrandom Mechanisms of actionStudies available?? SafetyStudies available?? ExcitabilityFacilitation/inhibitionFacilitation Spontaneous activityModulationSynchronisation?Desynchronisation? Learning+++ Clinical applicationStudies available??

Thanks for your attention