Seizure onset and offset pattern determine the entrainment of the cortex and substantia nigra in the nonhuman primate model of focal temporal lobe seizures

Abstract

Temporal lobe (TL) epilepsy is the most common form of drug-resistant epilepsy. A major focus of human and animal studies on TLE network has been the limbic circuit and the structures composing the temporal lobe. However, there is also evidence suggesting an active role of the basal ganglia in the propagation and control of temporal lobe seizures. Evidence suggests that the network involved in temporal lobe seizure may depend on their onset and offset pattern but studies on the relationship between the patterns and extralimbic activity are limited. Here, we characterize the involvement of the substantia nigra (SN) and somatosensory cortex (SI) during temporal lobe seizures induced in two nonhuman primates (NHP). The seizure onset and offset patterns were manually classified and spectral power and coherence were calculated. We then analyzed the three first and last seconds of the seizure as well as 3-second segments of recorded in pre-ictal and post-ictal periods and compared the changes based on the seizure onset and offset patterns. Our results demonstrated an involvement of the SN and SI dependent on the seizure onset and offset pattern. We found that seizures with both low amplitude fast activity (LAF) and high amplitude slow activity (HAS) onset patterns were associated with an increase in activity of the SN while the change in activity was limited to LAF seizures in the SI. However, the increase of HPC/SI coherence was similar for both type of onset, while the increase in HPC/SN coherence was specific to the farther-spreading LAF onset pattern. As for the role of the SN in seizure cessation, we observed that the coherence between the HPC/SN was reduced during burst suppression (BS) compared to other termination phases. Additionally, we found that this coherence returned to normal levels after the seizure ended, with no significant difference in post-ictal periods among the three types of seizure offsets. This result suggests that the SN might be involved differently in the termination of the BS seizure pattern. This study constitutes the first demonstration of temporal lobe seizures entraining the SN in the primate brain. Moreover, these findings provide evidence that this entrainment is dependent on the seizure onset pattern and support the hypothesis that the SN might play a role in the maintenance and termination of some specific temporal lobe seizure.