London cerebenet dec 2013 2

• 1. Cerebellar systems PhysiologyBen-Gurion University Beer-ShevaErasmus MC RotterdamDirect Current Stimulation: What is it and what does it do? Opher Donchin

2. Thanks up frontMaarten FrensJos Van Der GeestRick Van Der VlietClaire VerhageSuman DasPeter HollandEric Avila 3. Direct current stimulation What is it? Well, thats obvious, isnt it? What does it do? How does it effect neurons? How does it effect behavior? How does it work? 4. tDCS sells! Overclock your head! www.foc.us 5. Everyone is doing it!http://www.youtube.com/watch?v=6CZE6fq2nnk 6. So what is tDCS? Trans cranial direct current stimulation Passing electric current through the brain For clinical effects Depression, chronic pain, rehabilitation Or sub-clinical effects Cognitive improvements Affective improvements 7. The torpedo fish Scribonius Largus 43-48 AD On the scalp for headache Galen, 131-410 AD Ibn-Sidah, 11th century Electric catfish Studied by Walsh, 1773 Begins electrophysiology Followed up by Galvani Volta Priori Clin Neurophysiol 2003www.fragmentsoftime.com/45FishPlate.htm 8. Rebirth of tDCS Lippold and Redfearn, 1964 Effect on mood Low current, long stimulation Reproducible? Long term effects? Costain BJP 1964 9. tDCS affects cortical excitability Measure effect of 7-13 min of tDCS on EMG evoked by TMS over MI Much larger currents Nitsche Neurology 2001 10. tDCS has dissociable effects on MI and cerebellumGalea Cerebral Cortex 2010 11. SFN this year Opposite effects Panouilleres SFN 2013 12. We get no effect at all Pilot data 13. But we do for saccade adaptation In 5/7 subjects 14. And in a categorization task Prefrontal cortexCerebellum Deciding if a square is category 1 or category 2 15. Summary: tDCS in humans Huge media presence Storied history Potential clinical relevance Effect on learning Effect after stimulation is over Variable results Especially across laboratories 16. Animal models of tDCS Polarization of cortex affects excitability Reversibly Long after polarization ends Dependent on protein synthesisBindman J Physiol 1964 17. Effect of DCS depends on BDNF DCS effect is NMDA dependent Cre/floxed BDNF gene excision TrkB BDNF cognate receptor TrkBF616A knockin TrkB inactivated by 1NMPP1 18. Combining electrophysiology and behavior Animal behavioral model of tDCS Combine behavioral model with electrophysiology Focus on cerebellum 19. Compensatory eye movements (CEM) 20. In vivo DCS system 21. tDCS effect on VOR adaptationTest blockTest block 22. Dose effect Highest magnitude causes 132 uAmp32 uAmpTest block Reduction Or Reversal 23. MutantWild typeReversed effect in LTP imparimentTest block 24. Firing rate (sp/s) Firing rate (sp/s)ElectrophysiologyTime (min)Time (min) 25. Normalized firing rateConsistent reversal in mutant miceTime (min)Time (min) 26. Summary of results Humans Like everybody: Our tDCS results are variable Animals Polarity dependent increase in VOR adaptation rate Reversed in mutants Polarity dependent increase in firing rate Reversed in mutants 27. What is tDCS Effects on neural excitability Reproducible Polarity dependent Predictable Effects on behavior Occasionally strong Variable across laboratories In need of better control Clinical effects Under furious investigation 28. How does it work? Drive cascades that depend on membrane voltage Still need to explain: Increased intensity reverses effect Reversed effect for LTP-deficient mice High variability of behavioral results 29. Final thanks!Maarten FrensJos Van Der GeestRick Van Der VlietClaire VerhageSuman DasPeter HollandEric Avila 30. And to the audience!