title: Investigation of linear coupling between single-event blood flow responses and interictal discharges in a model of experimental epilepsy.
abstract: A successful outcome of epilepsy neurosurgery relies on an accurate delineation of the epileptogenic region to be resected. Functional magnetic resonance imaging (fMRI) would allow doing this noninvasively at high spatial resolution. However, a clear, quantitative description of the relationship between hemodynamic changes and the underlying epileptiform neuronal activity is still missing, thereby preventing the systematic use of fMRI for routine epilepsy surgery planning. To this aim, we used a local epilepsy model to record simultaneously cerebral blood flow (CBF) with laser Doppler (LD) and local field potentials (LFP) in rat frontal cortex. CBF responses to individual interictal-like spikes were large and robust. Their amplitude correlated linearly with spike amplitude. Moreover, the CBF response added linearly in time over a large range of spiking rates. CBF responses could thus be predicted by a linear model of the kind currently used for the interpretation of fMRI data, but including also the spikes' amplitudes as additional information. Predicted and measured CBF responses matched accurately. For high spiking frequencies (above approximately 0.2 Hz), the responses saturated but could eventually recover, indicating the presence of multiple neurovascular coupling mechanisms, which might act at different spatiotemporal scales. Spatially, CBF responses peaked at the center of epileptic activity and displayed a spatial specificity at least as good as the millimeter. These results suggest that simultaneous electroencephalographic and blood flow-based fMRI recordings should be suitable for the noninvasive precise localization of hyperexcitable regions in epileptic patients candidate for neurosurgery.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Rechereche 6193, 13402 Marseille Cedex 20, France. ivo.vanzetta@incm.cnrs-mrs.fr
authors.forename: Ivo
authors.initials: I
authors.lastname: Vanzetta
authors.forename: Corey
authors.initials: C
authors.lastname: Flynn
authors.forename: Anton I
authors.initials: AI
authors.lastname: Ivanov
authors.forename: Christophe
authors.initials: C
authors.lastname: Bernard
authors.forename: Christian G
authors.initials: CG
authors.lastname: Bénar
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000098:blood supply* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000473:pathology* / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology*; D018756:GABA Antagonists / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted / Q000379:methods; D017078:Laser-Doppler Flowmetry / Q000379:methods; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010100:Oxygen / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018756:GABA Antagonists; D010100:Oxygen; D001640:Bicuculline