Abstracts

Rationale:
The ability to record simultaneously infraslow activity (< 0.1 Hz) and higher frequencies (0.1-600 Hz) using the same recording electrode would particularly benefit epilepsy research. However, commonly used metal microelectrode technology is not well suited for recording infraslow activity. The ability to record ‘DC’ shifts at seizure onset will aid investigations into seizure initiation and could provide additional biomarkers for identification of seizure onset zones. Examination of post-seizure spreading depolarisations could provide valuable insight in seizure termination and mechanisms underlying SUDEP.  Here we use flexible graphene microtransistor arrays to concurrently record infraslow and high frequency neuronal activity in awake rodents in models of acute seizures and established epilepsy.
Method:
We implanted graphene transistor arrays, either a 16 channel epidural array over visual/somatosensory cortex, and/or a 14 channel penetrating probe through visual cortex to hippocampus in awake head-fixed mice. To induce epileptiform activity and seizures, chemoconvulsant (200nl of 50mM 4-AP, or 250nl of 10mM Picrotoxin) was injected into the visual cortex.    We implanted transistor arrays into the somatosensory cortex of WAG-Rij rats, a rodent model of absence epilepsy, and obtained chronic full-bandwidth recordings over a 10-week period, correlating preceding infraslow activity with spike-wave-discharge induction.  Finally we implanted transistor arrays into a rat model of occipital lobe epilepsy recording spontaneous seizures and spreading depolarizations.
Results:
We show that graphene transistor arrays can reliably record and map with high spatial resolution seizures, post-ictal spreading depolarisation, and high frequency activity (sharp wave ripples and HFO’s) across and through cortical laminae to the CA1 layer of the hippocampus in a mouse model of chemically-induced seizures. We demonstrate functionality of chronically implanted devices over 10 weeks by recording with high fidelity spontaneous spike-wave discharges and associated infraslow activity in a rat model of absence epilepsy. We demonstrate that some spontaneous seizures are associated with spreading depolarisations in awake chronically epileptic rats.
Conclusion:
Altogether, our work highlights the suitability of this technology for in-vivo electrophysiology research, in particular, to examine the contributions of infraslow activity to seizure initiation and termination.
Funding:
:This work has been funded by the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 785219 (Graphene Flagship). R.W. is funded by a Senior Research Fellowship awarded by the Worshipful Company of Pewterers