Modulating seizure-permissive states with weak electric fields

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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
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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.
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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
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IElectricField Electric Field Gcoupling
Cell polarization
Slope ? Gcoupling
Electric Field
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IElectricField Electric Field Gcoupling
Cell polarization
Slope ? Gcoupling
Electric Field
DC Uniform
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IElectricField Electric Field Gcoupling
Cell polarization
Slope ? Gcoupling
Electric Field
Depolarized cell compartments
Hyper-polarized cell compartments
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IElectricField Electric Field Gcoupling
Cell polarization
Slope ? Gcoupling
Electric Field
Hyper-polarized cell compartments
DC UniformField
Gcoupling 0
Depolarized cell compartments
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? Gcoupling
Cell polarization
Slope ? Gcoupling
IElectricField Electric Field Gcoupling
Electric Field
Bikson, Jefferys 2004 CA1 0.1 Deans, Jefferys
2007 CA3 0.2 Radman, Bikson 2009 Cortical
Neuron lt0.5
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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
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Network Gamma and Stimulation Methods
Tonic gamma
Brain Slice
Physiological Computational Model
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DC fields
6 mV / mm
Adaptation?
-6 mV / mm
Adaptation?
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AC fields
28 Hz (6 mV / mm)
Sub-harmonics?
Deans et al. 2008
2 Hz (4 mV / mm)
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Monophasic AC Fields
2 Hz AC (6 mV / mm) DC 6 mV/mm
2 Hz AC (6 mV / mm) - DC 6 mV/mm
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Computational Results
Slice
Qualitative / Quantitative reproduction of brain
slice data set (AC, DC, ACDC)Physiological
variables and parametersSimulation effects only
pyramidal neurons (soma)Adaptation,
sub-harmonics, modulationExtracellular,
intracellular
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Mechanism
In
In
Py
Py
In
In
carbachol
carbachol
Py
Py
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Mechanism
In
In
Py
Py
In
In
carbachol
carbachol
Py
Py
Electric field
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General Approach
Gamma
In vitro model electric fields? Computational
models
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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