Pawel Kudela, Piotr J. Franaszczuk, Gregory K. Bergey
Department of Neurology, Johns Hopkins University School of Medicine and Johns Hopkins Epilepsy Center, Johns Hopkins Hospital , Baltimore, Maryland.
RATIONALE: Determinations of the localization of neocortical epileptic
foci are limited by the spatial resolution of existing methods. High temporal
resolution methods are needed to differentiate ictal onsets from areas of
early regional spread to facilitate localization in patients undergoing presurgical
evaluations. We developed a computational model of epileptic foci in simulated
neural networks with the goal of modeling difficult to localize clinically
relevant events associated with seizure origination from areas with rapid
regional spread.
METHODS: Our model incorporates: 1) an array of excitatory neurons
capable of reproducing the spread of bursting activity and 2) a small sub-population
or sub-network which triggers the activity in the network array. Neurons
are modeled using a conductance-based model and realistic synaptic connections
are
simulated. Connections between neurons in the array are local e.g. each neuron
receives inputs from neighboring neurons only. This network is capable of
reproducing the spread of bursting activity. To simulate the epileptic focus,
an additional sub-population of neurons is incorporated into the network
array.
This sub-network is comprised of neurons capable of generating endogenous
bursts (model 1) or has the built-in structures of connections capable of
maintaining self- sustained oscillations (model 2).
RESULTS: In both types of models of the epileptic focus we observed
recurrent waves of bursting activity spreading through the network array.
In the first model when intrinsically bursting neurons stimulate with the
same period and phase postsynaptic neurons in the array we observed strictly
periodic waves of
bursting activity spreading through the network array. The frequency of propagating
waves is determined by the recovery time of neurons from afterhyperpolarization
and by the frequency of burst occurrence in
intrinsically bursting neurons in the triggering subpopulation. When the
number of intrinsically bursting neurons involved in triggering of the activity
increases (e.g. the area of projection increases), the spatiotemporal pattern
of activity is recurrent. In instances of activation of the network array
by an "epileptic circuit" (model 2) single pulse stimulation of one neuron
in the triggering network produces persistent activity in this network, which
drives the postsynaptic neurons in the network array. The number of
active postsynaptic neurons in the area of the projection of the focal ictal
activity changes in time. In this type of focus (model 2) induced spatiotemporal
patterns of activity in the network array are sensitive to oscillations in
the area of projection from the focus.
CONCLUSIONS: The presented model can clearly reveal differences
in the pattern of activity in the triggering zone (model epileptic focus)
and in the surrounding network. This model reproduces synchronous bursting
events in network arrays when the population of neurons in the focus (participating
in the origination of ictal events) is relatively constant (model 1) or varies
from moment to moment (model 2). These models can be helpful in investigations
of the nature of ictal or non-ictal events near the region of ictal onset.
Supported by NIH grant NS 38958
Epilepsia Vol. 43 , (Suppl. 7) , 2002