Insights into the Mechanisms of Absence Seizure Generation Provided by EEG with Functional MRI

Abstract

Absence seizures (AS) are brief epileptic events characterized by loss of awareness with subtle motor features. They may be very frequent, and impact on attention, learning, and memory. A number of pathophysiological models have been developed to explain the mechanism of absence seizure generation, which relies heavily on observations from animal studies. Studying the structural and functional relationships between large-scale brain networks in humans is only practical with non-invasive whole brain techniques. EEG with functional MRI (EEG-fMRI) is one such technique that provides an opportunity to explore the interactions between brain structures involved in AS generation. A number of fMRI techniques including event-related analysis, time-course analysis, and functional connectivity (FC) have identified a common network of structures involved in AS. This network comprises the thalamus, midline, and lateral parietal cortex [the default mode network (DMN)], caudate nuclei, and the reticular structures of the pons. The main component displaying an increase in blood oxygen level dependent (BOLD) signal relative to the resting state, in group studies, is the thalamus while the most consistent cortical change is reduced BOLD signal in the DMN. Time-course analysis shows that, rather than some structures being activated or inactivated during AS, there appears to be increase in activity across components of the network preceding or following the electro-clinical onset of the seizure. The earliest change in BOLD signal occurs in the DMN, prior to the onset of epileptiform events. This region also shows altered FC in patients with AS. Hence, it appears that engagement of this network is central to AS. In this review, we will explore the insights of EEG-fMRI studies into the mechanisms of AS and consider how the DMN is likely to be the major large-scale brain network central to both seizure generation and seizure manifestations.

Are Absence Epilepsy and Nocturnal Frontal Lobe Epilepsy System Epilepsies of the Sleep/Wake System?

“…Concerning the initial appearance of the resting state network before absences [ 66 ] we can raise the possibility that it represents the precipitating vigilance level decrease found with other methods before the absences. Similar speculation is given by Carney and Jackson [ 90 ] who speak about the first appearance of default mode network (DMN) before the EEG discharges start, as a “permissive cortical event” known to be required for the occurrence of the clinical and/or EEG paroxysm, which could be identical with the precipitatory decrease of vigilance emphasized in the previous chapters.…”

Spike-and-Wave Discharges Are Not Pathological Sleep Spindles, Network-Level Aspects of Age-Dependent Absence Seizure Development in Rats

“…Recent technical improvements made it possible to observe cortical network dynamics around seizures and an increasing body of evidence suggest that hypersynchronous SWDs are not necessarily accompanied by cellular level hyperactivity (Carney and Jackson, 2014;McCafferty et al, 2018;Meyer et al, 2018) To understand how off-focus cortical neurons contribute to generalizing SWD-patterns, we investigated how neuronal spiking of motor and prefrontal cortices were related to the spontaneously emerging SWDs (Fig. 6A).…”

Brain correlates of spike and wave discharges in GLUT1 deficiency syndrome

“…By contrast, GLUT1DS revealed bilateral activation in the putamen and different premotor and parietal areas (Fig. 3A); this pattern in not generally reported in GGE, except for single cases description (see Carney and Jackson, 2014 as review). The consistency of 3–4 Hz GSWD associated hemodynamic changes in GGE across studies, further support that the mechanisms subserving GSWD generation in GLUT1DS involve different neural dynamics.…”