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Abstracts

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

Abstract number : 2.079
Submission category : 3. Neurophysiology / 3F. Animal Studies
Year : 2023
Submission ID : 434
Source : www.aesnet.org
Presentation date : 12/3/2023 12:00:00 AM
Published date :

Authors :
Presenting Author: Mark Connolly, PhD – Emory National Primate Research Center

Jennifer Jiang, N/A – Emory College of Arts and Sciences; Claire-Anne Gutekunst, PhD – Emory University School of Medicine; Robert Gross, MD, PhD – Emory University School of Medicine; Annaelle Devergnas, PhD – Emory University School of Medicine

Rationale: Temporal 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 seizures in TL seizure models. These findings suggest the SN plays a role 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.

Methods: In two NHPs, recording electrodes were implanted in the hippocampus (HPC) and SN. 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 produces multiple spontaneous, nonconvulsive seizures over three to five hours. The seizure onset patterns were manually classified as LAF, HAS, or 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 three seconds before seizure offset. These changes were then compared between the LAF and HAS seizure types.

Results: During TL 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.

Conclusions: Our findings suggest that the SN may be entrained by TL seizures secondary to the SI during the farther spreading LAF seizures, which supports the theory that the SN plays a role in the generalization and/or maintenance of TL seizures and helps explains the anti-ictogenic effect of SN inhibition.

Funding:

UG3-NS100559



Neurophysiology