Multimodalin vivorecording using transparent graphene microelectrodes illuminates spatiotemporal seizure dynamics at the microscale

Abstract

Neurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution.

Shaping the future of European epilepsy research: Final meeting report from EPICLUSTER

“…Ongoing breakthroughs are transforming our ability to model the human brain (Andersson et al, 2016;Chiaradia and Lancaster, 2020); neuroscience tools enable us to record and manipulate neurons in brain structures (Driscoll et al, 2021); the molecular landscape of the epileptic brain can be defined at unprecedented resolution (Kumar et al, 2022); genes can be selectively activated or deactivated in vivo (Colasante et al, 2020) (Boivin et al, 2018) and preclinical research (Carroll et al, 2022), and tools are available for biomedical researchers to implement PPI (Maccarthy et al, 2019). The commitment to and uptake of PPI is, however, variable across diseases, geography and discipline.…”