Investigation of Linear Coupling Between Single-Event Blood Flow Responses and Interictal Discharges in a Model of Experimental Epilepsy

Abstract

Vanzetta I, Flynn C, Ivanov AI, Bernard C, Bénar CG. Investigation of linear coupling between single-event blood flow responses and interictal discharges in a model of experimental epilepsy. J Neurophysiol 103: 3139 -3152, 2010. First published March 24, 2010 doi:10.1152/jn.01048.2009. 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 ϳ0.2 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.

Interneurons contribute to the hemodynamic/metabolic response to epileptiform discharges

“…3A). As we previously reported (Vanzetta et al 2010), we observed a 2-s delay between the ED events and the maximal amplitude of blood flow perfusion. Furthermore, the tissue oxygen response was delayed by 2.5 s; however, a 750-ms delay is to be expected from the time response of the oxygen probe (Fig.…”

“…The amplitude of EDs was a good predictor of both CBF amplitude, confirming our previous work (Vanzetta et al 2010), and the oxygen response. Importantly, the baseline level of neuronal activity, as quantified by the inter-ED interval, was also an excellent predictor of both CBF and PO 2 amplitude fluctuations.…”

“…Importantly, the baseline level of neuronal activity, as quantified by the inter-ED interval, was also an excellent predictor of both CBF and PO 2 amplitude fluctuations. This is not surprising, as one expects some saturation of both the CBF and PO 2 responses for high regimes of bicuculline-induced discharges (Vanzetta et al 2010). CBF and oxygen are limited by maximal dilation and maximal PO 2 supply, and when baseline approaches these values the amplitudes of transient responses decrease.…”

“…To measure CBF as locally as possible, we used a needle probe (Perimed probe 411) with a 0.15-mm gap between the emitting and collecting light fibers (Vanzetta et al 2010). The probe was mounted on a three-axis micromanipulator (M-3333, Narishige Scientific Instrument Lab, Tokyo, Japan) attached to a magnetic stand (GJ-8, Narishige) mounted on an antivibration table and thus remained undisturbed throughout the experiment.…”

“…CBF and oxygen are limited by maximal dilation and maximal PO 2 supply, and when baseline approaches these values the amplitudes of transient responses decrease. This is an important consideration when using so-called fractional units-that is, when signal fluctuations are normalized by the baseline level (⌬signal/signal)-as is often done (Matsuura et al 2000;Vanzetta et al 2010). Our results show that when such fluctuations have large absolute value caution is required because both the numerator and the denominator can contribute to variations in the ⌬signal/signal ratio (Zhelev and Bakalova 2002).…”