Cortical spreading depression and the pathogenesis of brain disorders: a computational and neural network-based investigation.

This paper reviews our recent studies of the role of cortical spreading depression (CSD) in the pathogenesis of brain disorders. Our investigation is a computational one, involving the development and utilization of a complex neuro-metabolic model of the interactions assumed to occur in the cortex during the passage of multiple CSD waves. Incorporating these neuro-metabolic changes of CSD within a neural network model of normoxic cortex produces cortical activation patterns during the passage of a CSD wave that, projected onto the visual fields, resemble the visual hallucinations observed during the migraine aura. When focal ischemia is simulated with the model, the evoked CSD waves are found to affect the expansion of the infarction into the ischemic penumbra. Our findings support the hypothesis that CSD does play an important pathogenic role in these and other neurological disorders, and suggest additional experimental studies that may further substantiate it.