Brain Source Imaging in Preclinical Rat Models of Focal Epilepsy using High-Resolution EEG Recordings

Abstract

Electroencephalogram (EEG) has been traditionally used to determine which brain regions are the most likely candidates for resection in patients with focal epilepsy. This methodology relies on the assumption that seizures originate from the same regions of the brain from which interictal epileptiform discharges (IEDs) emerge. Preclinical models are very useful to find correlates between IED locations and the actual regions underlying seizure initiation in focal epilepsy. Rats have been commonly used in preclinical studies of epilepsy 1 ; hence, there exist a large variety of models for focal epilepsy in this particular species. However, it is challenging to record multichannel EEG and to perform brain source imaging in such a small animal. To overcome this issue, we combine a patented-technology to obtain 32-channel EEG recordings from rodents 2 and an MRI probabilistic atlas for brain anatomical structures in Wistar rats to perform brain source imaging. In this video, we introduce the procedures to acquire multichannel EEG from Wistar rats with focal cortical dysplasia, and describe the steps both to define the volume conductor model from the MRI atlas and to uniquely determine the IEDs. Finally, we validate the whole methodology by obtaining brain source images of IEDs and compare them with those obtained at different time frames during the seizure onset.

Dysfunction of Neurovascular/Metabolic Coupling in Chronic Focal Epilepsy

“…Localizing the seizure onset zones constitutes the most challenging aspects of using a chronic preclinical model of epilepsy. In this paper, we localized cortical irritative zones by performing brain current source imaging from scalp EEG recording [25]. Then, we obtained invasive intracranial recordings (electrophysiological -LFP; optical -CBF, CBV and [Deoxy-Hb] through a craniotomy created on top of these irritative zones.…”

Histological Characterization of Inter Ictal Epileptiform Discharges Generating Brain Regions using a Preclinical Model of Focal Cortical Dysplasia

“…Rat model for FCD created by prenatal treatment of methylazoxymethanol acetate (MAM) has a potential to mimic the pathologic and clinical features of FCD. We have provided extensive evidence for the validity of this chronic epileptic model using EEG data (Bae et al, 2015), IED-evoked fMRI response , and intracranial recordings (Song et al 2016). This model gave us insights about the cellular and molecular mechanisms of epileptogenesis which are evident with similar markers observed human FCD subjects.…”

“…Our results support the importance for a precise classification of IED markers from EEG recordings to determine the IED-generating irritative regions in a rat with focal epilepsy and further to evaluate their relationship with the underlying mechanisms for seizure initiation (Song Y, et al, 2014). In addition, it has been shown that EEG source localization for such specific IEDs showed a good correspondence with the respective BOLD activation and deactivation regions (Bae J, et al, 2015).…”

“…However, it can be applied to other rodent types with respective standard format of atlas including mouse (Hawrylycz M, et al, 2014), Sprague-Dawley rats (Schweinhardt P, et al, 2003), and Paxinos and Watson rats (Schwarz A, et al, 2006). We have provided extensive evidence for the validity of the used MAM-PILO chronic epileptic model using EEG data (Bae et al, 2015), IED-evoked fMRI response , and intracranial recordings (Song et al 2016). …”

“…Unfortunately, there are no previous systematic studies to characterize the pathophysiological mechanisms and abnormal cellular substrates in these irritative areas since histological data are available only from the final resective zones. To address this issue we applied a combination of EEG brain imaging described by Bae et al (2015) using cutting-edge technology for high-density scalp EEG in rodents and histological analysis on a chronic rat model of focal cortical dysplasia. Post-mortem brain sections were stained for anatomical, functional and inflammatory biomarkers.…”