Interictal spikes can be generated by blocking GABAA receptor-mediated inhibition. The nature of the hemodynamic activities associated with interictal spikes in acute models of focal epilepsy based on GABA deactivation has not been determined. We analyzed systemic changes in hemodynamic signals associated with interictal spikes generated by acute models of focal epilepsy. Simultaneous ElectroCorticoGraphy (ECoG) and Near-InfraRed Spectroscopy (NIRS) recordings were obtained in vivo from adult Sprague-Dawley rat brain during semi-periodic focal interictal spikes induced by local cortical application of low doses of Penicillin G (PG) and Bicuculline Methiodide (BM) as GABA deactivation agents. The Finite Impulse Response deconvolution technique was used to estimate the profile of hemodynamic changes in oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) concentrations associated with interictal ECoG spikes in each rat. Our results show that, in both acute models of focal epilepsy, the hemodynamic changes associated with interictal spikes were characterized by pre-spike and post-spike primary NIRS responses, and recovery periods with slight differences in amplitude and latency. The pre-spike period starting at least 2 s prior to the onset of ECoG spikes was characterized by a significant decrease in HbO concomitant with an increase in HbR with respect to baseline. The post-spike primary NIRS response exhibited the expected changes described according to the classical view of neurovascular coupling, i.e., a significant increase in HbO and a significant decrease in HbR in response to interictal spikes. The recovery period was characterized by a decreased HbO signal and an increased HbR signal, followed by a return to baseline. Compared to the BM epilepsy model, the PG model was more stable and showed lower variability in the shape, amplitude and latency of the components of spike-related hemodynamic changes. Our findings support a prominent role for pre-spike hemodynamic changes in the initiation of interictal spikes. The mechanism of interactions between neuronal and vascular networks during the pre-spike period constitutes a complex process, resulting in increased sensitivity of the epileptogenic focus to induce neuronal spiking.
Keywords: Electrocorticography; Epilepsy; GABA deactivation; Interictal spike; Near-infrared spectroscopy; Neurovascular coupling; Rats.