What is a Seizure? Insights from Human Single-Neuron Recordings

Commentary Countless articles in the field of epilepsy begin with a statement such as: “Epileptic seizures are caused by an imbalance of cerebral excitation and inhibition. ” This seems to be a fundamental truth that is rarely questioned. The International League Against Epilepsy (ILAE) defines seizures as “excessive or synchronous neuronal activity”(1). Truccolo et al. report on single-neuron activity in humans before, during, and after seizures by utilizing microelectrode recordings. They find that neuronal firing during seizures is much more heterogeneous than we assumed and can probably not be explained based on a simple model of excitation and inhibition. They implanted a 96-channel, tightly spaced microelectrode array in the neocortex of four patients (Neuroport, Blackrock Microsystems Inc., Salt Lake City, UT). The array was placed in an area that was likely to be resected in epilepsy surgery. It covered an area of 4 mm and recorded at a depth of 1 mm. They investigated single-neuron firing during eight seizures by routine intracranial EEG prior to epilepsy surgery. They distinguished between the interictal, preictal, ictal, and postictal periods. They found that neuronal firing rate increased in 45.5% of all recorded neurons and decreased in 9.9%. Firing patterns were heterogeneous and followed no uniform pattern. What is the Beginning and the End? At the onset of the seizure, neuronal firing did not uniformly increase as expected in a purely excitatory event. Heterogeneity of firing patterns increased at seizure onset, as reflected by a measure of variance, the Fano Factor (Figure 1). The authors suggest their findings argue “against homogeneous runaway excitation or widespread paroxysmal depolarization as the primary mechanism underlying seizure initiation. ” However, firing patterns within patients seemed reproducible but neuronal recordings over prolonged periods of time are often too unstable to assess with certainty. The authors determine seizure onset as classically defined by intracranial electrocorticography via visual inspection (Figure 1) and show that in the preictal period, there is already a modulation in baseline firing as compared with the interictal state. Preictal firing rate changes are seen less frequently than ictal firing changes. Preictal firing could increase (11.8% of all neurons) or decrease (7.5% of neurons). These findings raise the question of whether there is a clear-cut seizure onset at all. Where does the preictal period end and the seizure start? Seizure onset may not be a single event in time but rather a continuum. The authors propose that the changes in preictal firing may ultimately lead to a viable seizure prediction algorithm. After decades of searching for a reliable seizure prediction algorithm, this may be another venue to pursue. Rightly, the authors caution that their data are too premature to be conclusive. More single-unit recordings of seizures are necessary to test whether this is a workable algorithm. We may have an easier time with determining the end of a seizure. The authors’ second major observation is the “abrupt Single-Neuron Dynamics in Human Focal Epilepsy.