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Absence seizures are common within many different epilepsies and span all the ages. Even though absence seizures were described more than three centuries ago advances associated with its classification, pathophysiology, genetics, treatment, prognosis, and associated co-morbidities continue to be made.

Summary:Purpose: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. Methods: Blood-oxygenation-level-dependent (BOLD) fMRI in the brain was measured by using T 2 * -weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using γ -butyrolactone (GBL; 200 mg/kg, intraperitoneal).Results: The corticothalamic circuitry, critical for spike-wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes.Conclusions: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents. Key Words: Absence seizure-fMRIEpilepsy-Imaging-GHB.Typical absence seizures consist of multiple, brief (≤20 s) impairments of consciousness with characteristic bilaterally synchronous 3-Hz spike-wave discharges (SWDs) on electroencephalography (EEG). A typical absence seizure is manifested behaviorally as a "staring spell" and can be accompanied by atonic postures such as drooping of the head and/or automatisms such as lip smacking. The incidence of absence seizures in the United States is 1.9 to 8 per 100,000, usually occurring in children between the ages of 4 years and adolescence, with girls affected twice as often as boys (1).Early studies on cats showed that electrical stimulation to the midline and intralaminar nuclei of the thalamus at a frequency of 3 Hz produced SWDs on EEG (2). This finding was corroborated after the discovery of identical 3-Hz SWDs in children with deep recording electrodes Accepted May 7, 2003. Address correspondence and reprint requests to Dr. J.R. Tenney at University of Massachusetts Medical School, CCNI Building, 55 Lake Avenue North, Worcester MA 01655, U.S.A. E-mail: jeffrey. tenney@umassmed.edu in the thalamus (3). These early seminal studies pointed to the thalamus as the initiation site of SWDs, and recent work with rodent models has shown that corticothalamic interactions are involved in the pathogenesis of absence seizures.γ -Hydroxybutyric acid (GHB) is a naturally occurring metabolite of the inhibitory neurotransmitter γ -aminobutyric acid (GABA). Normal rats given an intraperitoneal (i.p.) injection of GHB will show all the behavioral and electrophysiological signs of generalized absence seizure (4). Synchronized bursting activity from recording electrodes in the somatosensory ventroba...

Functional magnetic resonance imaging (fMRI) was used to assess the effects of cocaine on brain activation in fully conscious rats. Methods were developed to image cocaine-induced changes in blood-oxygen-level-dependent (BOLD) signal without the peripheral cardiac and respiratory complications associated with psychostimulant administration. Using spin echo planar imaging (EPI), conscious rats were imaged in a 4.7 T spectrometer prior to and following the intracerebroventricular injection of cocaine (20 microg) in artificial cerebrospinal fluid (10 uL). Within 5 min of injection, there was a significant increase in BOLD signal intensity in the substantia nigra, ventral tegmental area, nucleus accumbens, dorsal striatum and prefrontal cortex, as compared to vehicle controls. Minimal negative BOLD signal changes were observed in response to cocaine and no significant perturbations in normal cardiovascular and respiratory function. These findings demonstrate the technical feasibility of studying psychostimulant-induced brain activity using functional MRI in conscious rats.

Summary:Purpose: EEG-triggered functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during spontaneous spike-and-wave discharges (SWDs) in an epileptic rat strain under awake conditions.Methods: Spontaneous absence seizures from 10 WAG/Rij rats were imaged by using T 2 * -weighted echo planar imaging at 4.7Tesla. fMRI of the blood-oxygenation-level-dependent (BOLD) signal was triggered based on EEG recordings during imaging. Images obtained during spontaneous SWDs were compared with baseline images.Results: Significant positive BOLD signal changes were apparent in several areas of the cortex and several important nuclei of the thalamus. In addition, no negative BOLD signal was found in any brain area.Conclusions: We have shown that EEG-triggered BOLD fMRI can be used to detect cortical and thalamic activation related to the spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These results draw an anatomic correlation between areas in which increased BOLD signal is found and those in which SWDs have been recorded. In addition, no negative BOLD signal was found to be associated with these spontaneous SWDs. We also demonstrated the technical feasibility of using EEG-triggered fMRI in a genetic rat model of absence seizure. Key Words: Absence seizure-fMRIEpilepsy-WAG/Rij-Imaging.Typical absence seizures consist of multiple, brief (≤20 s) impairments of consciousness with characteristic bilaterally synchronous 3-Hz spike-and-wave discharges (SWDs) on electroencephalography (EEG). A typical absence seizure is manifested behaviorally as a "staring spell" and can be accompanied by atonic postures such as drooping of the head and/or automatisms such as lip smacking (1).Genetic rat models of absence epilepsy have been studied for many years and are thought to mimic more accurately the spontaneous seizures of human epilepsy than do drug-induced animal models. The strain of rats named WAG/Rij (Wistar Albino Glaxo strain bred in Rijswijk, the Netherlands) have been inbred for absence-like characteristics for >100 generations, which implies that they are homozygous (2,3). This strain exhibits spontaneous SWDs that have a frequency of 7 to 11 Hz, duration of 1 to 45 s, and an amplitude of 200 to 1,000 µV (4). As in the human condition, EEG changes are accompanied by immobile behavior and staring. Age-related changes Accepted February 18, 2004. Address correspondence and reprint requests to Dr. J.R. Tenney at University of Massachusetts Medical School, CCNI Building, 55 Lake Avenue North, Worcester, MA 01655, U.S.A. E-mail: jeffrey.tenney@umassmed.edu in the number of SWDs have been found. At an age of 75 days, only 17% of rats experience a single SWD in a 4-h period, compared with 140 and 245 days, at which SWDs affected 83% and 100% of rats, respectively (5).Electrophysiology recordings of the WAG/Rij model have been used to uncover the neural structures responsible for the generation and propagation of SWDs. Many of these studies have implicated the coupling of ...