Elsevier

NeuroImage

Volume 19, Issue 3, July 2003, Pages 627-636
NeuroImage

Regular article
Simultaneous electroencephalographic recording and functional magnetic resonance imaging during pentylenetetrazol-induced seizures in rat

https://doi.org/10.1016/S1053-8119(03)00138-1Get rights and content

Abstract

Truly simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) were registered in curarized rats injected with convulsive doses of pentylenetetrazol (PTZ, 65 mg/kg, sc). Rigorous control of physiological parameters like body temperature and ventilation with control of blood gasses helped to avoid potential interference between systemic parameters, and central PTZ-induced blood oxygenation level-dependent (BOLD) changes. Simultaneous EEG/fMRI recordings demonstrated progressive epileptiform EEG discharges with concomitant BOLD changes, the latter gradually affecting most of the fore- and midbrain. Approximately 15 min after PTZ injection, the first BOLD contrast changes mainly occurred in neocortex, and coincided with the first minor EEG alterations. Most regions that displayed BOLD changes were regions with reportedly high GABAA receptor densities. Full-blown epileptiform discharges occurred on the EEG tracing, approximately 30 min after PTZ injection, and coincided with bilateral positive and/or negative BOLD contrast changes in cortical and subcortical regions. Behavioral observations demonstrated the first of several generalized clonic or clonic-tonic seizure episodes to occur also around this time. Approximately 90 min after injection, the electrographic paroxysms gradually decreased in amplitude and duration, whereas the BOLD signal changes still extended with alternating positive and negative traces, and spread to subcortical regions like caudate-putamen and globus pallidus.

Introduction

The interest in methods to combine the advantages of electroencephalogram (EEG) and magnetic resonance imaging (MRI) techniques has grown over the last few years. EEG recording reveals a subject’s overall brain state as well as specific transient events (e.g., epileptic discharges), and is characterized by high temporal, but low spatial resolution. MRI recording, on the other hand, provides anatomical detail as well as some physiological information (e.g., tissue water homeostasis, tissue perfusion, and brain activation) with high spatial, but low temporal resolution. Simultaneous recording of EEG and MRI would enable the registration of brain activity with high spatial as well as temporal resolution. However, severe pollution of the EEG tracing due to gradient switching during the MRI sequence remained, until recently, the main problem for truly simultaneous EEG/MRI Ives et al 1993, Warach et al 1996.

Methods that combine EEG and functional MRI (fMRI) have been successfully used to determine the focus of epileptogenic activity in patients suffering from different kinds of seizure disorders Seeck et al 1998, Patel et al 1999, Symms et al 1999, Krakow et al 1999, Krakow et al 2001, Jackson et al 1994, Detre et al 1995. However, in these latter studies, EEG and fMRI were either performed intermittently for consecutive comparison, or changes in EEG were used to trigger fMRI registration. Truly simultaneous acquisition of EEG and fMRI would enable the monitoring of neuronal and hemodynamic activities. Several other applications would also benefit from the possibility of simultaneous and complete coverage of electrographic changes and regional distribution of brain activity. Such recordings could be made during evoked potential recording (e.g., visual-evoked potentials; Bonmassar et al., 2001) or during cortical spreading depression (Busch et al., 1995). The use of fMRI and simultaneous EEG in a pharmacological stimulation protocol might offer new possibilities for the study of brain functions and drug–receptor interactions (for review, see Leslie and James, 2000).

Neurological and hemodynamic changes were studied for the first time noninvasively using in vivo fMRI and simultaneous EEG recording in a rodent model of generalized seizures. A specially designed filtering scheme was applied successfully to eliminate EEG distortions due to gradient switching. Until the present, brain activations resulting from PTZ induced seizures were studied with histological and electrophysiological techniques. Regarding the mechanism of PTZ-induced seizures, we observed asymmetrical signal changes in this study that may relate to similar observations in the human condition of epilepsy (Laich et al., 1997).

Section snippets

Animals and preparatory procedures

Male Wistar rats (mean body weight, 350 g) were used and housed under standard laboratory conditions (constant temperature and humidity, chow and water ad lib). In a preliminary experiment to establish the effective convulsive dose of PTZ, different doses (29, 43, and 65 mg/kg) of PTZ were injected subcutaneously (sc). The minimal dose (CD95) for the induction of generalized clonic seizures in all rats was determined according to Weil (1952). Next, a behavioral study was again performed outside

PTZ-induced behavioral changes

A small group of rats was injected sc with different doses of PTZ in the MRI room with background scanner noise. Based on these preliminary observations, CD95 for the appearance of generalized clonic seizures under these conditions was estimated to be 65 mg/kg. Subsequently, 10 freely moving male rats were injected sc with a single dose of 65 mg/kg PTZ for systematic observation of PTZ-induced behavioral alterations. This dose of PTZ was indeed shown to evoke generalized clonic seizures in all

Discussion

In this report, we describe an application of truly simultaneous EEG and fMRI acquisition. The EEG signals, obtained during fMRI acquisition, were heavily disturbed due to static as well as dynamic magnetic field interference, cardiac pulse interference, etc. To remove these artifacts, we applied a restoration scheme developed by Sijbers et al. (1999). In contrast to what was claimed by Allen (Allen et al., 2000), this algorithm has proven to be very successful in removing interference

Acknowledgements

This work was supported by the EC (CRAFT project Nr. BES2-5214), the National Science Foundation (FWO, project Nr G.0401.00), and RAFO funds from the University of Antwerp to AvdL.

RD is postdoctoral researcher with the National Science Foundation (FWO) Flanders. NVC is a grant holder from the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT-V).

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