Abstracts

Rationale: Observations suggest that focal epilepsies may involve widespread brain networks, and generalised epilepsies may have focal cortical regions that drive seizure onset (J Neurosci 2002;22(4):1480-95). These observations have contributed to a reappraisal of the classification of epilepsies, and seizures, and underpinned the concept that seizures may emerge from network dynamics (Epilepsia 2010; 51(4): 676-685 & Epilepsia 2012; 53(5): 771-778). We hypothesise that whether an EEG discharge appears focal or generalised is driven by the pattern of connections in brain networks, irrespective of the presence of focal brain abnormality. Here, we explore this question using a computational brain model. Methods: We have previously described a brain model consisting of grey-matter "nodes" and white matter "connections" (J Math Neurosci 2012; 2(1):1). Dynamics in the nodes are governed by mathematical equations which allow a bistable state; one state represents normal low-amplitude EEG activity, the other state high-amplitude EEG ictal discharges. Transitions between the states are driven by intrinsic noise in each node and the synchronising influences felt from other nodes via the connections in the network. Nodes were modelled with "normal" dynamics, in which transition from normal to pathological activity had a low probability; in some instances we modelled nodes with "hyperexcitable" dynamics, in which the transition from normal to pathological activity had a higher probability. We explored the effects of altering connectivity structure versus the effects of introducing an "abnormal" brain region, and the interactions between these factors. Results: Computer simulations demonstrated that EEG discharges representing either generalized or focal seizures arose purely as a consequence of subtle changes in network structure, without the requirement for any localized pathological brain region. Further we found that introducing a pathological region gave rise to focal, secondary generalized or primary generalized seizures depending on the network structure. We illustrate this in the Figure: (a) and (b) show patterns of connectivity between normal nodes which result in normal EEG activity. (c) and (d) show the consequence of introducing a hyperexcitable node (in red) to the networks in (a) and (b) respectively: the pattern of connectivity in (c) results in generalised discharges, but the pattern of connectivity in (d) results in focal discharges. (e) and (f) show that a set of normal brain nodes can generate generalised (seen in (e)) or focal discharges (seen in (f)) entirely as a result of network connectivity structure, without an abnormal node. Counter-intuitively, we found that decreasing connectivity between regions of the brain increased the frequency of seizure-like activity. Conclusions: Our findings may enlighten current controversies surrounding the concepts of focal and generalized epilepsy, and help to explain recent observations in genetic animal models and human epilepsies, where loss of white matter pathways was associated with the occurrence of seizures.