title: Time-frequency analysis of single pulse electrical stimulation to assist delineation of epileptogenic cortex.
abstract: Epilepsy surgery depends on reliable pre-surgical markers of epileptogenic tissue. The current gold standard is the seizure onset zone in ictal, i.e. chronic, electrocorticography recordings. Single pulse electrical stimulation can evoke epileptic, spike-like responses in areas of seizure onset also recorded by electrocorticography. Recently, spontaneous pathological high-frequency oscillations (80-520 Hz) have been observed in the electrocorticogram that are related to epileptic spikes, but seem more specific for epileptogenic cortex. We wanted to see whether a quantitative electroencephalography analysis using time-frequency information including the higher frequency range could be applied to evoked responses by single pulse electrical stimulation, to enhance its specificity and clinical use. Electrocorticography data were recorded at a 2048-Hz sampling rate from 13 patients. Single pulse electrical stimulation (10 stimuli, 1 ms, 8 mA, 0.2 Hz) was performed stimulating pairs of adjacent electrodes. A time-frequency analysis based on Morlet wavelet transformation was performed in a [-1 s : 1 s] time interval around the stimulus and a frequency range of 10-520 Hz. Significant (P = 0.05) changes in power spectra averaged for 10 epochs were computed, resulting in event-related spectral perturbation images. In these images, time-frequency analysis of single pulse-evoked responses, in the range of 10-80 Hz for spikes, 80-250 Hz for ripples and 250-520 Hz for fast ripples, were scored by two observers independently. Sensitivity, specificity and predictive value of time-frequency single pulse-evoked responses in the three frequency ranges were compared with seizure onset zone and post-surgical outcome. In all patients, evoked responses included spikes, ripples and fast ripples. For the seizure onset zone, the median sensitivity of time-frequency single pulse-evoked responses decreased from 100% for spikes to 67% for fast ripples and the median specificity increased from 17% for spikes to 79% for fast ripples. A median positive predictive value for the evoked responses in the seizure onset zone of 17% was found for spikes, 26% for ripples and 37% for fast ripples. Five out of seven patients with <50% of fast ripples removed by resection had a poor outcome. A wavelet transform-based time-frequency analysis of single pulse electrical stimulation reveals evoked responses in the frequency range of spikes, ripples and fast ripples. We demonstrate that time-frequency analysis of single pulse electrical stimulation can assist in delineation of the epileptogenic cortex using time-frequency single pulse-evoked fast ripples as a potential new marker.
authors: Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors: Maryse A
authors: MA
authors: van 't Klooster
authors: Maeike
authors: M
authors: Zijlmans
authors: Frans S S
authors: FS
authors: Leijten
authors: Cyrille H
authors: CH
authors: Ferrier
authors: Michel J A M
authors: MJ
authors: van Putten
authors: Geertjan J M
authors: GJ
authors: Huiskamp
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping / Q000379:methods*; D002540:Cerebral Cortex / Q000503:physiopathology*; D002648:Child; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male