Post on 27-Jan-2016
description
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
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.
Network Gamma and Stimulation Methods
Brain Slice
450 μM acute rat hippocampal slice20 μM carbacholCA3 extra/intracellular electrophysiologyUniform “weak” electric field stimulation (DC, AC, acute, open loop)
‘Izhikevich’ single compartment CA3 neurons800 pyramidal and 200 inhibitory neuronsAll-to-all synaptic coupling, weighted strengthsElectric Field polarizes pyramidals as:
“Physiological” Computational Model
IElectricField = Electric Field * Gcoupling
IElectricField = Electric Field * Gcoupling
Electric Field
Cell polarizationSlope → Gcoupling
IElectricField = Electric Field * Gcoupling
Electric Field
Cell polarizationSlope → Gcoupling
DC Uniform
DC Uniform
Field
IElectricField = Electric Field * Gcoupling
Electric Field
Cell polarizationSlope → Gcoupling
Hyper-polarized cell compartments
Depolarized cell compartments
DC Uniform
Field
IElectricField = Electric Field * Gcoupling
Electric Field
Cell polarizationSlope → Gcoupling
Hyper-polarized cell compartments
DC Uniform
Field
Depolarized cell compartments
Gcoupling = 0
? Gcoupling
Electric Field
Cell polarizationSlope → Gcoupling
Bikson, Jefferys 2004 CA1 ~ 0.1 Deans, Jefferys 2007 CA3 ~ 0.2 Radman, Bikson 2009 Cortical Neuron <0.5
IElectricField = Electric Field * Gcoupling
IElectricField = Electric Field * Gcoupling
“Physiological” Computational Model
Brain Slice
Gcoupling (field freq) ← t =RC
450 μM acute hippocampal slice20 μM carbacholCA3 extra/intracellular electrophysiologyUniform “weak” electric field stimulation (DC, AC, acute, open loop)
‘Izhikevich’ single compartment CA3 neurons800 pyramidal and 200 inhibitory neuronsAll-to-all synaptic coupling, weighted strengthsElectric Field polarizes pyramidals as:
Network Gamma and Stimulation Methods
“Tonic” gamma
“Physiological” Computational Model
Brain Slice
Network Gamma and Stimulation Methods
DC fields
-6 mV / mm
6 mV / mm
Adaptation?
Adaptation?
AC fields
2 Hz (4 mV / mm)
28 Hz (6 mV / mm)
Sub-harmonics?
Modulation?
Deans et al. 2008
Monophasic ‘AC’ Fields
2 Hz AC (6 mV / mm) + DC 6 mV/mm
2 Hz AC (6 mV / mm) - DC 6 mV/mm
Computational Results
Qualitative / Quantitative reproduction of brain slice data set (AC, DC, AC+DC)
Physiological variables and parameters
Simulation effects only pyramidal neurons (soma)
Adaptation, sub-harmonics, modulation
Extracellular, intracellular
Slice
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carbachol
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carbachol
Mechanism
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carbachol
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Electric field
carbachol
Mechanism
DC
28 Hz AC
General Approach
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Electric field
carbachol
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Electric field
carbachol
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Electric field
carbachol
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Electric field
carbachol
Gamma
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Epileptic
In vitro model + electric fields→ Computational models
KainateIn
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noise
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potassium
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Conclusions
“Weak” electric fields can modulate active gamma oscillations
Interactions between the cellular and network level determine responses
Response is system/state specific (physiology, pathophysiology)
Reduced (e.g. single compartment) but “physiological” and parameterized (Gcoupling, field) computer models may guide rational epilepsy electrotherapy