Local neuronal excitation and global inhibition during epileptic fast ripples in humans

International audienceAbstract Understanding the neuronal basis of epileptic activity is a major challenge in neurology. Cellular integration into larger scale networks is all the more challenging. In the local field potential, interictal epileptic discharges can be associated with fast ripples (FRs, 200-600 Hz), which are a promising marker of the epileptogenic zone. Yet, how neuronal populations in the epileptogenic zone and in healthy tissue are affected by FRs remain unclear. Here, we used a novel “hybrid” macro-micro depth electrode in nine drug-resistant epileptic patients, combining classic depth recording of local field potentials (macrocontacts) and two or three tetrodes (four microwires bundled together) enabling up to 15 neurons in local circuits to be simultaneously recorded. We characterized neuronal responses (190 single units) with the timing of FRs (2233 FRs) on the same hybrid and other electrodes that target other brain regions. Micro-wire recordings reveal signals that are not visible on macro-contacts. While FRs detected on the closest macro-contact to the tetrodes were always associated with FRs on the tetrodes, 82% of FRs detected on tetrodes were associated with detectable FR on the nearest macro-contact. Moreover, neuronal recordings were taken in and outside the epileptogenic zone of implanted epileptic subjects and they revealed an interlay of excitation and inhibition across anatomical scales. While FRs were associated with increased neuronal activity in very local circuits only, they were followed by inhibition in large-scale networks (beyond the epileptogenic zone, even in healthy cortex). Neuronal responses to FRs were homogeneous in local networks but differed across brain areas. Similarly, post-FR inhibition varied across recording locations and subjects and was shorter than typical inter-FR intervals, suggesting that this inhibition is a fundamental refractory process for the networks. These findings demonstrate that FRs engage local and global networks, including healthy tissue, and point to network features that pave the way for new diagnostic and therapeutic strategies. They also reveal how even localized pathological brain dynamics can affect a broad range of cognitive functions