The Entrainment of the Substantia Nigra During Temporal Lobe Seizures is Dependent on the Seizure Onset Pattern

Abstract

AbstractRationaleTemporal lobe (TL) epilepsy is the most common form of drug-resistant epilepsy. While the limbic circuit and the structures composing the TL have been a major focus of human and animal studies on TL seizures, there is also evidence suggesting that the basal ganglia have an active role in the propagation and control of TL seizures. Studies in patients have shown that TL seizures can cause changes in the oscillatory activity of the basal ganglia when the seizures spread to extratemporal structures. Preclinical studies have found that inhibition of the substantia nigra pars reticulata (SN), a major output structure of the basal ganglia, can reduce the duration and severity of TL seizures in animal models. These findings suggest the SN plays a role critical in the maintenance or propagation of TL seizures. Two stereotyped onset patterns commonly observed in TL seizures are low-amplitude fast (LAF) and high-amplitude slow (HAS). Both onset patterns can arise from the same ictogenic circuit, however seizures with LAF onset pattern typically spread farther and have a larger onset zone than HAS. Therefore, we would expect LAF seizures to entrain the SN more so than HAS seizures. Here, we use a nonhuman primate (NHP) model of TL seizures to confirm the implication of the SN in TL seizure and to characterize the relationship between TL seizure onset pattern and the entrainment of the SN.MethodsRecording electrodes were implanted in the hippocampus (HPC) and SN in 2 NHPs. One subject was also implanted with extradural screws for recording activity in the somatosensory cortex (SI). Neural activity from both structures was recorded at a 2 kHz sampling rate. Seizures were induced by intrahippocampal injection of penicillin, which produced multiple spontaneous, nonconvulsive seizures over 3-5 hours. The seizure onset patterns were manually classified as LAF, HAS or other/undetermined. Across all seizures, spectral power and coherence were calculated for the frequency bands 1–7 Hz, 8–12 Hz and 13–25 Hz from/between both structures and compared between the 3 seconds before the seizure, the first 3 seconds of the seizure, and the 3 seconds before seizure offset. These changes were then compared between the LAF and HAS onset patterns.ResultsDuring temporal lobe seizures, the 8–12 Hz and 13–25 Hz power in the SN along with the 1–7 Hz and 13–15 Hz power in the SI was significantly higher during onset than before the seizure. Both the SN and SI had an increase in coherence with the HPC in the 13–25 Hz and 1– 7 Hz frequency ranges, respectively. Comparing these differences between LAF and HAS, both were associated with the increase in the HPC/SI coherence, while the increase in HPC/SN increase was specific to LAF.ConclusionOur findings suggest that the SN may be entrained by temporal lobe seizures secondary to the SI during the farther spreading of LAF seizures, which supports the theory that the SN plays a role in the generalization and/or maintenance of temporal lobe seizures and helps explains the anti-ictogenic effect of SN inhibition.