Responses to single pulse electrical stimulation identify epileptogenesis in the human brain in vivo

Abstract

The aim of the present study was to investigate in vivo cortical excitability in the human brain. We studied 45 consecutive patients with refractory epilepsy in whom subdural or intracerebral electrodes were implanted for assessment prior to epilepsy surgery. We compared cortical responses to single pulse stimulation (up to 8 mA, 1 ms duration) in areas where seizure onset occurred, with responses recorded elsewhere. Two main types of responses were seen: (i) 'early responses', spikes and/or slow waves starting within 100 ms after the stimulus which were observed in most regions in all patients; and (ii) 'delayed responses', spikes or sharp waves occurring between 100 ms and 1 s after stimulation which were seen in some regions in 27 patients. The distributions of early and delayed responses were compared with the topography of seizure onset. Whereas early responses were seen in most regions and seem to be a normal response of the cortex to single pulse stimulation, the distributions of delayed responses were significantly associated with the regions where seizure onset occurred. We conclude that the presence of delayed responses can identify regions of hyperexcitable cortex in the human brain. The study of delayed responses may improve our understanding of the physiology and dynamics of neuronal circuits in epileptic tissue and may have an immediate clinical application in assessment of candidates for surgical treatment of epilepsy.

Mechanisms of physiological and epileptic HFO generation

“…First, a requirement for firing precision of the order of milliseconds for synchronous action potentials to become visible at the local EEG is rarely met for the activity in the normal brain but becomes critical in the epileptic tissue due to its enhanced excitability. Hence, clinical data on evoked potentials from epileptic patients is thought to represent a mixture of postsynaptic currents and population spikes (Rutecki et al, 1989;Valentin et al, 2002;Wilson et al, 1990). These population spikes represent precise synchronous action potentials of pools of parallel-oriented principal neurons (Andersen et al, 1971;Kloosterman et al, 2001).…”

Physiology of functional and effective networks in epilepsy

“…CCEPs provide a unique opportunity to directly study differences in electrophysiology between normal and epileptogenic cortex in the human brain, and have shown potential as a diagnostic tool in epilepsy. Valentin et al (2002) used single pulse electrical stimulation to stimulate the IOZ and recorded responses within and outside of it. They identified both early (<100 ms) and late evoked responses, and determined that while early responses showed a similar distribution in normal and pathological tissue, late responses, which presented like after-discharges, were linked to the IOZ in patients with temporal lobe epilepsy (TLE).…”

“…Indeed, stimulation parameters can vary widely both within and between studies. For example, studies focused upon defining connectivity (Matsumoto et al, 2004;Entz et al, 2014;Keller et al, 2014a) use 1 Hz stimulation frequencies, whereas studies focusing (Valentin et al, 2002;Lacruz et al, 2007) use much longer intervals (8-10 s). Stimulation intensity also varies considerably across the above-mentioned studies, with an application of current that ranges from 4 to 10 mA.…”

Evoked directional network characteristics of epileptogenic tissue derived from single pulse electrical stimulation

“…Single pulse electrical stimulation (SPES) is a clinical method for identifying the epileptogenic zone independent of spontaneous seizures, mainly because of the ability to provoke delayed responses (DRs) (Valentín et al, 2002; van ‘t Klooster et al, 2011). During the SPES protocol, electrocortical stimuli are systematically applied to pairs of adjacent electrodes on the subdural electrode grid and correlated responses in all other electrodes are analyzed.…”