Download 6 mV / mm

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 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
Cell polarization
Slope → Gcoupling
IElectricField = Electric Field * Gcoupling
Electric Field
Cell polarization
Slope → Gcoupling
IElectricField = Electric Field * Gcoupling
Electric Field
DC Uniform
DC
Uniform
Field
Cell polarization
Slope → Gcoupling
IElectricField = Electric Field * Gcoupling
Electric Field
Depolarized cell compartments
DC
Uniform
Field
Hyper-polarized cell compartments
Cell polarization
Slope → Gcoupling
IElectricField = Electric Field * Gcoupling
Electric Field
Hyper-polarized cell compartments
DC
Uniform
Field
Gcoupling = 0
Depolarized cell compartments
Cell polarization
IElectricField = Electric Field * Gcoupling
Bikson, Jefferys 2004
Deans, Jefferys 2007
Radman, Bikson 2009
Slope → Gcoupling
Electric Field
CA1 ~ 0.1
CA3 ~ 0.2
Cortical Neuron <0.5
? Gcoupling
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
Network Gamma and Stimulation Methods
“Tonic” gamma
Brain Slice
“Physiological” Computational Model
DC fields
6 mV / mm
Adaptation?
-6 mV / mm
Adaptation?
AC fields
28 Hz (6 mV / mm)
Sub-harmonics?
Deans et al. 2008
2 Hz (4 mV / mm)
Modulation?
Monophasic ‘AC’ Fields
2 Hz AC (6 mV / mm) + DC 6 mV/mm
2 Hz AC (6 mV / mm) - DC 6 mV/mm
Slice
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
Mechanism
In
Py
In
carbachol
Py
Mechanism
DC
In
Py
In
carbachol
Py
28 Hz AC
Electric field
General Approach
In
Gamma
Kainate
Py
In
Py
In
Py
In
carbachol
Py
In
Py
Electric field
In
noise
Py
Epileptic
In
Py
In vitro model + electric fields
→ Computational models
In
Py
In
potassium
Py
Py
In
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