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Modulating seizure-permissive states with weak electric fields

Modulating seizure-permissive states with weak electric fields. Marom Bikson Davide Reato, Thomas Radman, Lucas Parra. Neural Engineering Laboratory - Department of Biomedical Engineering The City College of New York of CUNY. Rational Epilepsy Electrotherapy.

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Modulating seizure-permissive states with weak electric fields

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  1. Modulating seizure-permissive states with weak electric fields Marom Bikson Davide Reato, Thomas Radman, Lucas Parra Neural Engineering Laboratory - Department of Biomedical Engineering The City College of New York of CUNY

  2. Rational Epilepsy Electrotherapy Specific Objective: Characterize the modulation of gamma-band network activity by weak electric fields. Epilepsy Control Rationale: Changes in gamma activity may be indicative of a pre-seizure. Early detection and stimulation may control seizures. General Approach: Can the mechanisms of electrical modulation be accurately described to then facilitate rational control strategies. Methods: Stimulation of gamma oscillations in brain slices to characterize acute effects. “Physiological” computational neuronal modeling to describe modulation.

  3. Network Gamma and Stimulation Methods Brain Slice 450 μM acute rat hippocampal slice 20 μM carbachol CA3 extra/intracellular electrophysiology Uniform “weak” electric field stimulation (DC, AC, acute, open loop) “Physiological” Computational Model ‘Izhikevich’ single compartment CA3 neurons 800 pyramidal and 200 inhibitory neurons All-to-all synaptic coupling, weighted strengths Electric Field polarizes pyramidals as: IElectricField = Electric Field * Gcoupling

  4. Cell polarization IElectricField = Electric Field * Gcoupling Slope → Gcoupling Electric Field

  5. DC UniformField Cell polarization IElectricField = Electric Field * Gcoupling Slope → Gcoupling Electric Field DC Uniform

  6. DC UniformField Cell polarization IElectricField = Electric Field * Gcoupling Slope → Gcoupling Electric Field Depolarized cell compartments Hyper-polarized cell compartments

  7. Cell polarization IElectricField = Electric Field * Gcoupling Slope → Gcoupling Electric Field Hyper-polarized cell compartments DC UniformField Gcoupling = 0 Depolarized cell compartments

  8. Cell polarization ? Gcoupling Slope → Gcoupling IElectricField = Electric Field * Gcoupling Electric Field Bikson, Jefferys 2004 CA1 ~ 0.1Deans, Jefferys 2007 CA3 ~ 0.2Radman, Bikson 2009 Cortical Neuron <0.5

  9. Network Gamma and Stimulation Methods Brain Slice 450 μM acute hippocampal slice 20 μM carbachol CA3 extra/intracellular electrophysiology Uniform “weak” electric field stimulation (DC, AC, acute, open loop) “Physiological” Computational Model ‘Izhikevich’ single compartment CA3 neurons 800 pyramidal and 200 inhibitory neurons All-to-all synaptic coupling, weighted strengths Electric Field polarizes pyramidals as: IElectricField = Electric Field * Gcoupling Gcoupling (field freq) ← t =RC

  10. Network Gamma and Stimulation Methods “Tonic” gamma Brain Slice “Physiological” Computational Model

  11. 6 mV / mm DC fields Adaptation? -6 mV / mm Adaptation?

  12. Modulation? 28 Hz (6 mV / mm) AC fields Sub-harmonics? Deans et al. 2008 2 Hz (4 mV / mm)

  13. 2 Hz AC (6 mV / mm) + DC 6 mV/mm Monophasic ‘AC’ Fields 2 Hz AC (6 mV / mm) - DC 6 mV/mm

  14. Slice Computational Results Qualitative / Quantitative reproduction of brain slice data set (AC, DC, AC+DC)Physiological variables and parametersSimulation effects only pyramidal neurons (soma)Adaptation, sub-harmonics, modulationExtracellular, intracellular

  15. Mechanism In In Py Py In In carbachol carbachol Py Py

  16. Mechanism DC 28 Hz AC In In Py Py In In carbachol carbachol Py Py Electric field

  17. Epileptic Gamma General Approach In vitro model + electric fields→ Computational models

  18. Conclusions “Weak” electric fields can modulate active gamma oscillationsInteractions between the cellular and network level determine responsesResponse is system/state specific (physiology, pathophysiology)Reduced (e.g. single compartment) but “physiological” and parameterized (Gcoupling, field) computer models may guide rational epilepsy electrotherapy

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