Full-bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene microtransistor depth neural probes

Abstract

Mapping the entire frequency bandwidth of brain electrophysiological signals is of paramount importance for understanding physiological and pathological states. The ability to record simultaneously DC-shifts, infraslow oscillations (<0.1Hz), typical LFP signals (0.1-80 Hz) and higher frequencies (80-600 Hz) using the same recording site would particularly benefit preclinical epilepsy research and could provide clinical biomarkers for improved seizure onset zone delineation. However, commonly used metal microelectrode technology suffers from instabilities that hamper the high-fidelity of DC-coupled recordings, which are needed to access signals of very low frequency. Here, we use flexible graphene depth neural probes (gDNP), consisting of a linear array of graphene microtransistors, to concurrently record DC-shifts and high frequency neuronal activity in awake rodents. We show that gDNPs can reliably record and map with high spatial resolution seizures, pre-ictal DC-shifts and seizure associated spreading depolarizations together with higher frequencies through the cortical laminae to the hippocampus in a mouse model of chemically-induced seizures. Moreover, we demonstrate functionality of chronically implanted devices over 10 weeks by recording with high fidelity spontaneous spike-wave discharges and associated infraslow oscillations in a rat model of absence epilepsy. Altogether, our work highlights the suitability of this technology for in vivo electrophysiology research, and in particular epilepsy research, by allowing stable and chronic DC-coupled recordings.

Converging Mechanisms of Epileptogenesis and Their Insight in Glioblastoma

“…One such example of which is graphene-based solution-gated field-effect transistors (gSGFETs). gSGFETs have the potential to fill this technology gap as they offer the means to record SDs, either independently or concurrently with high-frequency activity, both epi- and intra-cortically with high spatiotemporal fidelity (Hébert et al, 2018 ; Masvidal-Codina et al, 2019 , 2021 ; Bonaccini Calia et al, 2021 ). The potential for SDs to exacerbate tissue damage and promote mechanisms of hyperexcitability in GBM could have consequences for disease progression, prognosis, and resistance to therapies.…”

The advantages of mapping slow brain potentials using DC‐coupled graphene micro‐transistors: Clinical and translational applications

“…A similar layer‐specific localisation of ‘active’ DC shifts preceding seizures could be identified. 11 Ictal DC shifts can be differentiated into active shifts that precede the seizure and passive shifts that follow the intense neuronal firing at seizure onset. 12 Active DC shifts are of particular interest for both clinical and basic research, as they provide an electrophysiological biomarker for seizure onset zone localisation, 13 and they can further provide a quantifiable parameter to investigate the mechanisms underlying seizure initiation.…”

“… 14 Chronic implantation of gSGFET probes into the somatosensory cortex of a rat model of absence epilepsy revealed that spontaneous spike‐and‐wave discharges (5–9 Hz) were phase‐coupled to an infraslow oscillation (ISO < 0.1 Hz) most prominent in the superficial layers, suggesting that these ISOs open susceptibility windows for seizure initiation. 11 …”

Digital reconstruction of infraslow activity in human intracranial ictal recordings using a deconvolution-based inverse filter

“…Next, we wished to test a signal that was of biological relevance. A recording of a hippocampal seizure in a mouse that was available through a public repository was used [14] (Methods). This seizure was originally recorded with a DC amplifier, which allowed preservation and recording of low frequency components.…”

“…Signals were generated with a sampling rate of 1000 samples/s. The mouse hippocampal seizure recording was downloaded from a publicly available repository (https://doi.org/10.5281/zenodo.5655535) [14] in HDF5 format, downsampled to 1000 samples/s, and converted to a *.mat file (Fig. 6A1).…”