Gap junctions modulate seizures in a mean-field model of general anesthesia for the cortex |
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Authors: | Moira L Steyn-Ross D Alistair Steyn-Ross Jamie W Sleigh |
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Institution: | (1) School of Engineering, University of Waikato, Hamilton, 3240, New Zealand;(2) Waikato Clinical School, University of Auckland, Waikato Hospital, Hamilton, 3240, New Zealand |
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Abstract: | During slow-wave sleep, general anesthesia, and generalized seizures, there is an absence of consciousness. These states are
characterized by low-frequency large-amplitude traveling waves in scalp electroencephalogram. Therefore the oscillatory state
might be an indication of failure to form coherent neuronal assemblies necessary for consciousness. A generalized seizure
event is a pathological brain state that is the clearest manifestation of waves of synchronized neuronal activity. Since gap
junctions provide a direct electrical connection between adjoining neurons, thus enhancing synchronous behavior, reducing
gap-junction conductance should suppress seizures; however there is no clear experimental evidence for this. Here we report
theoretical predictions for a physiologically-based cortical model that describes the general anesthetic phase transition
from consciousness to coma, and includes both chemical synaptic and direct electrotonic synapses. The model dynamics exhibits
both Hopf (temporal) and Turing (spatial) instabilities; the Hopf instability corresponds to the slow (≲8 Hz) oscillatory
states similar to those seen in slow-wave sleep, general anesthesia, and seizures. We argue that a delicately balanced interplay
between Hopf and Turing modes provides a canonical mechanism for the default non-cognitive rest state of the brain. We show
that the Turing mode, set by gap-junction diffusion, is generally protective against entering oscillatory modes; and that
weakening the Turing mode by reducing gap conduction can release an uncontrolled Hopf oscillation and hence an increased propensity
for seizure and simultaneously an increased sensitivity to GABAergic anesthesia. |
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Keywords: | Seizure Gap junctions Mean-field cortical model Hopf oscillations Turing patterns Nonlinear interactions Phase coherence |
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