Dysfunction of neurovascular/metabolic coupling in chronic focal epilepsy

In this study, we aim to evaluate the mechanisms underlying the neuro-vascular/metabolic coupling in the epileptogenic cortices of rats with chronic focal epilepsy. To that end, we first analyzed intracranial recordings (electrophysiology, laser Doppler flowmetry and optical imaging) obtained from the seizure onset zones during ictal periods and then used these data to fit a metabolically-coupled balloon model. This biophysical model is an extension of the standard balloon model with modulatory effects of changes in tissue oxygenation, capillary dynamics and variable O2 extraction fraction. As previously reported using acute seizure models, we found that there is a significant higher contribution from high local field potential frequency bands to the cerebral blood flow (CBF) responses in the epileptogenic cortices during ictal neuronal activities. The hemodynamic responses associated with ictal activities were distance-dependent with regard to the seizure focus, though varied in profiles from those obtained from acute seizure models. Parameters linking the CBF and relative concentration of deoxy-hemoglobin to neuronal activity in the biophysical model were significantly different between epileptic and normal rats. In particular, we found that the coefficient associated with the strength of the functional hyperemic response was significantly larger in the epileptogenic cortices, although changes in hemoglobin concentration associated with ictal activity reflected the existence of a significantly higher baseline for oxygen metabolism in the epileptogenic cortices