Abstracts

Rationale: Localized cortical pathologies may be associated with the occurrence of focal epilepsy. This suggests that interactions between the atypical area of cortex and the surround may be important in the process of focal seizure origination. The objective of these studies was to demonstrate that the existence of the abnormal area (pathological or damaged), simulated in a neuronal network model, can promote the occurrence of recurrent and synchronous bursting activity in this network. Methods: We simulated activity in a model of a square area of neocortex. The network model consists of populations of excitatory and inhibitory neurons arranged into minicolumns (90 neurons synaptically connected), which are distributed in a plane. Interconnections between minicolumns are relatively spars so the entire network connectivity bears a general resemblance to a cortical laminar/columnar circuit. Each minicolumn represents a coherent source that can produce synchronized activity. The pathology in the network model is represented by the abnormal cluster of minicolumns. Inside the abnormal cluster, neuronal and synaptic characteristics differ from the characteristics of neurons outside this fragment, in the remaining network. Simulated abnormalities included alterations in the potassium channel characteristics ([K⁺]_o elevation), as well as partial loss of excitatory inputs in the atypical area (cortical deafferentation). Results: In a homogenous network, brief periods of activity, when epileptiform-like bursting spreads over the population of neurons have been observed. These momentary periods of neuronal activity, similar to interictal spikes, were initiated by random action potentials delivered to neurons and were terminated by afterhyperpolarization in neurons. In contrast, in the networks with a cluster of atypical minicolumns, interical-like spikes are followed by additional spikes resulting from the existence of the secondary neuronal activity patterns developing locally in the abnormal area. Neurons in the abnormal area often do not fire “in phase” with neurons in the surrounding area, which provides the mechanism for maintenance of the pathological neuronal activity in the entire network. While epileptiform bursting activity spreads over the population of neurons and normally ends quickly, the activity in the abnormal area can continue and recruit adjacent neurons to initiate another spread of bursting activity over the population of neurons. Conclusions: The existence of localized abnormality in the network alters the characteristics of the entire network response to brief activation. Simulations showed that the pattern of neuronal activation in the abnormal region is not consistent with spatiotemporal pattern of neuronal activation in the rest of the network. This lack of synchrony facilitates origination and the spread of neuronal bursting in the adjacent areas. This simulation demonstrates that localized abnormalities in the network resulting from channel-mediated current alterations or neuronal deafferentation may act as ictogenic focus. Supported by NIH grand NS051382