Abstracts

Rationale: In this study, we investigated how pharmacologically induced acute seizures evolve over time in the frequency, spatial, and temporal domains. We used a dimensionality reduction method developed in our group (Driscoll et al., 2021) on a multimodal dataset to identify prominent factors during a multi-hour recording. Then, we determined the weightings of input features in each factor. The dominant factors shifted as the seizure evolves towards status epilepticus.

Methods: 4-aminopyridine was applied on a cortical surface of the transgenic mouse expressing calcium indicator GCaMP6 in principal neurons. A custom transparent 16 channel graphene microelectrode was used to collect electrophysiological information from the cortical surface. Simultaneous widefield fluorescent calcium imaging was used to determine the extent of the seizure area and the rate of seizure expansion. In a separate preparation, activity from CA1 neurons was imaged by two-photon microscopy, while electrophysiological information was recorded from the transparent graphene electrode array placed under a cannula imaging window. Features such as phase-locked high gamma, proximity to the ictal wavefront, and local field potential correlation across channels, were extracted from the microECoG recordings and the calcium imaging dataset. The features were fed into a dimensionality reduction algorithm to determine key multimodal factors for representing seizure state.

Results: As the seizure evolves towards status epilepticus, higher frequency components showed higher power. While the spatial extent of the seizure did not change, the rate of seizure spread increased dramatically. Dimensionality reduction analysis showed that cyclical factors better fit the data when seizures in the pre-status epilepticus were separated from the ones occurring during status epilepticus.

Conclusions: Shifts in the dominant factors as the seizure enters status epilepticus indicate that there are fundamental differences between seizures in the initial stages that show a clear termination and seizures in status epilepticus. From this analysis, we hypothesize that the cellular activity during seizures will diverge between those that occur during status epilepticus and those that do not. Potentially, mechanisms to target for seizure termination will differ between these two groups of seizures as well.

Reference: Nicolette Driscoll, Richard E. Rosch, Brendan B. Murphy, Arian Ashourvan, Ramya Vishnubhotla, Olivia O. Dickens, A. T. Charlie Johnson, Kathryn A. Davis, Brian Litt, Danielle S. Bassett, Hajime Takano & Flavia Vitale, Multimodal in vivo recording using transparent graphene microelectrodes illuminates spatiotemporal seizure dynamics at the microscale. Commun. Biol. 4, 1–9 (2021).

Funding: Please list any funding that was received in support of this abstract.: NIH/NINDS R21 NS106434 (H.T. and F.V.) NSF Graduate Research Fellowship Program DGE 1321851 (N.D.).