Abstract
Spike-sorting algorithms have been used to identify the firing patterns of isolated neurons ('single units') from implanted electrode recordings in patients undergoing assessment for epilepsy surgery, but we do not know their potential for providing helpful clinical information. It is important therefore to characterize both the stability of these recordings and also their context. A critical consideration is where the units are located with respect to the focus of the pathology. Recent analyses of neuronal spiking activity, recorded over extended spatial areas using microelectrode arrays, have demonstrated the importance of considering seizure activity in terms of two distinct spatial territories: the ictal core and penumbral territories. The pathological information in these two areas, however, is likely to be very different. We investigated, therefore, whether units could be followed reliably over prolonged periods of times in these two areas, including during seizure epochs. We isolated unit recordings from several hundred neurons from four patients undergoing video-telemetry monitoring for surgical evaluation of focal neocortical epilepsies. Unit stability could last in excess of 40 h, and across multiple seizures. A key finding was that in the penumbra, spike stereotypy was maintained even during the seizure. There was a net tendency towards increased penumbral firing during the seizure, although only a minority of units (10-20%) showed significant changes over the baseline period, and notably, these also included neurons showing significant reductions in firing. In contrast, within the ictal core territories, regions characterized by intense hypersynchronous multi-unit firing, our spike sorting algorithms failed as the units were incorporated into the seizure activity. No spike sorting was possible from that moment until the end of the seizure, but recovery of the spike shape was rapid following seizure termination: some units reappeared within tens of seconds of the end of the seizure, and over 80% reappeared within 3 min (τrecov = 104 ± 22 s). The recovery of the mean firing rate was close to pre-ictal levels also within this time frame, suggesting that the more protracted post-ictal state cannot be explained by persistent cellular neurophysiological dysfunction in either the penumbral or the core territories. These studies lay the foundation for future investigations of how these recordings may inform clinical practice.See Kimchi and Cash (doi:10.1093/awv264) for a scientific commentary on this article.
Highlights
Action potentials are the means by which neurons send information rapidly throughout the brain
In the context of epilepsy, rather than questioning how neuronal firing relates to the outside world, one might ask what the firing patterns tell us about the local brain state, and how they relate to the timing and frequency of both interictal events and seizures (Verzeano et al, 1971; Ishijima, 1972; Babb and Crandall, 1976; Schmidt et al, 1976; Babb et al, 1987; Bower and Buckmaster, 2008)
There is a strong presumption that these changes should be apparent in extracellular recordings, but to check this explicitly, we made cell attached recordings from visually identified, layer 5, pyramidal neurons in brain slices prepared from young mice, during epileptiform events induced by removing Mg2 + ions from the bathing medium (0 Mg2 + model; Supplementary Fig. 4)
Summary
Action potentials are the means by which neurons send information rapidly throughout the brain. Technological advances in microelectrode arrays (MEAs) mean that we can gather data about many neurons simultaneously. These arrays were developed for use in brain–machine interfaces, and so the initial studies of their performance considered the long-term stability of recordings. Another study examined the stability of action potentials recorded on microelectrode arrays, used to interface a computer with human primary motor cortex, over a period of 2 years (Suner et al, 2005). There is little information, relating to the stability of unit isolation recorded using these MEAs in the acute/subacute time frame, as provided by their use in presurgical seizure monitoring
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