Effects of ketamine on EEG in baboons with genetic generalized epilepsy

Abstract

Ketamine, a noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist, used as an anesthetic has been reported to induce seizures both in humans and baboons predisposed to epilepsy. In this study, we aimed to characterize the acute effects of ketamine on scalp (sc-EEG) and intracranial EEG (ic-EEG) in the baboon, which offers a natural model of genetic generalized epilepsy (GGE). We evaluated the electroclinical response to ketamine in three epileptic baboons. The raw EEG data were analyzed within 10 min of intramuscular ketamine (5-6 mg/kg) administration. Earliest EEG changes occurred after 30 s in sc-EEG and after 15 s in ic-EEG of ketamine administration. These initial changes involved increased paroxysmal fast activity (PFA) followed by slowing, the latter emerging first occipitally, and then spreading more anteriorly. Generalized spike-and-wave discharges (GSWDs) were evident on both sc-EEG and ic-EEG within two minutes, but focal occipital discharges were already increased on ic-EEG after 15 s. Occipital slowing emerged on ic-EEG after 30 s, before spreading fronto-centrally and orbito-frontally. By 60-120 seconds post-injection, ic-EEG demonstrated a parieto-occipital burst suppression (BS), which was not noted on sc-EEG. Ketamine waves and seizures, especially if the latter were subclinical, also appeared earlier on ic-EEG. This study highlights the anesthetic and proconvulsant effects of ketamine originate in the occipital lobes before fronto-central regions. We speculate that NMDAR concentration difference in cortical regions, such as the occipital and frontal cortices, are mainly involved in the expression of ketamine's EEG effects, both physiological and epileptic.

Keywords: Anesthesia; Animal Models; Electroencephalography; Epilepsy; Ketamine.

Figure 1:. Electrode Map in B3

OF (orbitofrontal depth electrodes, GRD (frontoparietal grid electrodes), TP (temporoparietal strip electrodes), PO (parietooccipital strip electrodes) O occipital depth electrodes).

Figure 2:. Ketamine Effect on Interictal Scalp EEG

FP frontopolar, T(emporal), O(ccipital), C(entral), Lt eye (Left epicanthus), Rt eye (Right epicanthus), Arm (biceps), X3-A1 ECG channel. Panel A: EEG demonstrates intermittent generalized interictal epileptic discharges, and continuous generalized slowing. Panel B: Shows low-voltage fast activity alternating with ketamine waves.

Figure 3:. Ketamine Effect on Ictal Scalp EEG

FP frontopolar, T(emporal), O(ccipital), C(entral), Lt eye (Left epicanthus), Rt eye (Right epicanthus), Arm (biceps), X3-A1 ECG channel. Panel A: EEG demonstrates generalized spikes and polyspikes with myoclonic seizure. Panel B, C, D: Shows evolution of generalized tonic-clonic seizure. Panel B: shows onset; Panel C: Tonic phase; Panel D: Clonic phase

Figure 4:. Progression of Ketamine-Induced Changes on Scalp and Intracranial EEG

LGRD (left frontoparietal grid), LO (left occipital strip), RO (right occipital strip), RGRD (right frontoparietal grid), Sc-EEG: scalp EEG. Panel A: baseline recording comparing the intracranial and scalp EEG (bottom arrow). Panel B: shows occipital spikes and slowing; Panel C: dissociated EEG rhythms in the parieto-occipital regions and fronto-central regions; Panel D: Evolving burst suppression pattern in the occipital regions; Panel E: Tonic activity exhibited by baboon B2 clinically, noted with fronto-central fast activity with background suppression pattern.