Authors :
Presenting Author: Andrew Zayachkivsky, PhD – University of Utah
Erika Scholl, PhD – University of Utah
Daniel Barth, PhD – University of Colorado, Boulder
F. Edward Dudek, PhD – University of Utah
Rationale:
Research with animal models of epilepsy requires unequivocal identification of seizures in the electroencephalogram (EEG). In numerous rat models of epilepsy, high-amplitude oscillatory “spike-wave discharges” (SWDs; 9-12 Hz) with behavioral arrest are often reported to be spontaneous recurrent seizures (SRSs), based on some similarities in waveform and duration to seizures. However, these events were also previously found to occur in normal lab rats, and even in wild-caught rats (Taylor et al., 2019 J Neurosci 39:4829). SWDs with synchronous onsets in rats have been described as a model of absence, while SWDs with asynchronous or “focal” onsets have been reported to be non-convulsive seizures characteristic of acquired epilepsy. By examining the EEG in normal immature and adult Sprague-Dawley (SD) rats, and comparing them to actual seizures induced later with a chemo-convulsant compound in the same animals, this study provides further evidence that spontaneous SWDs are not seizures but instead are normal oscillatory brain activity.
Methods:
Postnatal day 14 (P14), P21, and P70 SD rats were implanted bilaterally with surface neocortical electrodes. After baseline recordings, repetitive seizures were induced with diisopropyl flourophosphate (DFP). Normal high-amplitude oscillatory brain activity from baseline recordings was quantitatively compared to DFP-induced seizures using power spectral density, principal component analyses, and other quantitative methods. This allowed comparison of normal SWD waveforms with seizures from the same animals.
Results:
Young adult SD rats (P70) had numerous SWDs that typically lasted 1-5 sec, but could persist for >20 sec. Similar SWDs were found in juvenile rats (P21-28), and even in P14 rat pups. The SWDs had high spectral power in the alpha band (9-12 Hz), distinct from theta oscillations (5-7 Hz) in normal background EEG. Most SWDs had synchronous onsets, but many were asynchronous. Unlike the SWDs with power predominantly in the alpha band, DFP-induced seizures involved a temporally evolving pattern of high-amplitude electrical activity across most frequency bands, including delta, theta, beta and gamma.
Conclusions:
Because SWDs with either synchronous or asynchronous onsets could be readily observed in virtually all control rats (as young as P14), synchronous-onset SWDs are not likely to be absence seizures, and similar SWDs with asynchronous onsets are unlikely to be focal-onset seizures (e.g., after traumatic brain injury); instead, they represent routine brain oscillations that can be found in virtually all rats (e.g., Taylor et al., 2019), even as early as P14. These data emphasize that correct identification of actual seizures depends heavily on the temporal pattern of the electrical activity, in addition to amplitude and duration of the event. Therefore, long-duration SWDs may have some similarities in waveform and amplitude to actual seizures, thus making it possible for misidentification of SWDs as seizures; however, SWDs are quantitatively different from seizures when examined across multiple frequencies.Funding: DoD W81XWH-14-C-0119 and W81XWH-22-1-0366