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Semelhante a London cerebenet dec 2013 2
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- 1. Cerebellar systems Physiology Ben-Gurion University Beer-Sheva Erasmus MC Rotterdam Direct Current Stimulation: What is it and what does it do? Opher Donchin
- 2. Thanks up front Maarten Frens Jos Van Der Geest Rick Van Der Vliet Claire Verhage Suman Das Peter Holland Eric Avila
- 3. Direct current stimulation • What is it? – Well, that’s obvious, isn’t 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 2003 www.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 cerebellum Galea 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 cortex Cerebellum • 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 synthesis Bindman 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
- 20. In vivo DCS system
- 21. tDCS effect on VOR adaptation Test block Test block
- 22. Dose effect • Highest magnitude causes 132 uAmp 32 uAmp Test block – Reduction – Or Reversal
- 23. Mutant Wild type Reversed effect in LTP impariment Test block
- 24. Firing rate (sp/s) Firing rate (sp/s) Electrophysiology Time (min) Time (min)
- 25. Normalized firing rate Consistent reversal in mutant mice Time (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 Frens Jos Van Der Geest Rick Van Der Vliet Claire Verhage Suman Das Peter Holland Eric Avila
- 30. And to the audience!