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

2. Electrical Stimulation in the 18th century

3. Electrical Stimulation in the 19th century

4. (1910)

5. Transcranial electrical stimulation (TES) 1980

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

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

8. Text Cortical DC-stimulation of the rat: effects during stimulation … Bindman et al. 1964 Baseline cathodalanodal

9. …and after-effects Bindman et al. 1964 cathodal anodal

10. After-effects are protein synthesis- dependent Gartside 1968

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

12. 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)

13. tDCS in humans

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

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

16. Reduced motor cortico-spinal excitability after cathodal tDCS 0.4 0.6 0.8 1.2 15101520253035404550556090120 min 1.0 Nitsche et al. 2003

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

18. 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

19. 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

20. 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

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

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

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

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

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

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

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

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

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

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

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

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

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

34. 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)

35. Recent developments tACStRNS

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

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

38. tRNS Terney et al. 2008 Motor cortex excitability Motor learning

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

40. Thanks for your attention