Abstract
Objective: Electrical impedance tomography (EIT) can be used to image impedance changes associated with epileptiform activity and so holds therapeutic potential for improving presurgical localisation of the ictal onset zone in patients with treatment-resistant epilepsy. There are two principal impedance changes which occur during seizures that may be imaged with EIT: (a) a fast, transient impedance decrease over milliseconds due to hypersynchronous neuronal depolarisation in individual ictal discharges; and (b) a larger, slow impedance increase caused by cell swelling over the course of the seizure. The magnitude of these signals is highly dependent on the carrier frequency of applied current used for obtaining impedance measurements. The purpose of this work was to characterise the frequency response of the fast and slow impedance changes during epileptiform activity. Approach: Seizures were induced in anaesthetised rats by electrically stimulating the cerebral cortex. During each seizure, impedance measurements were obtained by delivering 50 µA, through two electrodes on an epicortical array, at one of 20 frequencies in the 1–10 kHz range. Recordings were demodulated to determine the magnitude of fast and slow impedance responses at each frequency. Main results: The fast impedance change during averaged ictal discharges reached a maximal amplitude and signal-to-noise ratio (SNR) of −0.36% ± 0.05% and 50.2 ± 11.3, respectively, at 1355 Hz. At this frequency, the slow impedance change had an amplitude of 4.61% ± 1.32% and an SNR of 545 ± 125, which did not significantly change across frequency (p > 0.01). Significance: We conclude that the optimal frequency for imaging epileptiform activity is 1355 Hz, which maximises the SNR of fast neural changes whilst enabling simultaneous measurement of slow changes. These findings will inform future investigations aimed at imaging epilepsy in subcortical brain structures, where SNR is considerably reduced, and those using parallel, multi-frequency EIT.
Highlights
IntroductionImpedance changes during epileptiform activity A well-established increase in cerebral tissue impedance, which occurs over seconds, has been reported in several species during both chemically and electrically induced seizures in acute and chronic models of epilepsy (Van Harreveld and Schadé 1962, Elazar et al 1966, Rao 2000, Olsson et al 2006, Vongerichten et al 2016)
Seizures comprising a characteristic pattern of repeatable ictal discharges, which consisted of 5 Hz ictal spike-and-wave discharges that subsequently slowed to 2–3 Hz sharp waves, were reliably induced by electrical stimulation with 2 mA biphasic square-wave pulses in all animals
The requisite first step in assessing the frequency response of impedance changes associated with ictal discharges and seizures was to confirm that these events stayed consistent over time and were not affected by the frequency of current applied to obtain the impedance measurement
Summary
Impedance changes during epileptiform activity A well-established increase in cerebral tissue impedance, which occurs over seconds, has been reported in several species during both chemically and electrically induced seizures in acute and chronic models of epilepsy (Van Harreveld and Schadé 1962, Elazar et al 1966, Rao 2000, Olsson et al 2006, Vongerichten et al 2016) It is caused by cell swelling due to a disturbance in ion homeostasis which occurs as a result of the high metabolic demands of the intense neuronal activity underlying epilepsy (Andrew and MacVicar 1994, Dzhala et al 2000, Dreier et al 2011). A decrease in volume of the extracellular fluid due to cell swelling will, cause an increase in the measured tissue impedance
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