Hippocampal high-frequency electrographic activity (HFOs) represents one of the major discoveries not only in epilepsy research but also in cognitive science over the past few decades. A fundamental challenge, however, has been the fact that physiological HFOs associated with normal brain function overlap in frequency with pathological HFOs. We investigated the impact of a cognitive task on HFOs with the aim of improving differentiation between epileptic and non-epileptic hippocampi in humans. Hippocampal activity was recorded with depth electrodes in 15 patients with focal epilepsy during a resting period and subsequently during a cognitive task. HFOs in ripple and fast ripple frequency ranges were evaluated in both conditions, and their rate, spectral entropy, relative amplitude and duration were compared in epileptic and non-epileptic hippocampi. The similarity of HFOs properties recorded at rest in epileptic and non-epileptic hippocampi suggests that they cannot be used alone to distinguish between hippocampi. However, both ripples and fast ripples were observed with higher rates, higher relative amplitudes and longer durations at rest as well as during a cognitive task in epileptic compared with non-epileptic hippocampi. Moreover, during a cognitive task, significant reductions of HFOs rates were found in epileptic hippocampi. These reductions were not observed in non-epileptic hippocampi. Our results indicate that although both hippocampi generate HFOs with similar features that probably reflect non-pathological phenomena, it is possible to differentiate between epileptic and non-epileptic hippocampi using a simple odd-ball task.

1st Department of Neurology Brno Epilepsy Center St Anne's University Hospital and Medical Faculty of Masaryk University Pekařská 53 Brno 65691 Czech Republic

CEITEC Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Neurosurgery Brno Epilepsy Center St Anne's University Hospital and Medical Faculty of Masaryk University Brno Czech Republic

International Clinical Research Center St Anne's University Hospital Brno Czech Republic

School of Life and Health Sciences Aston University Birmingham UK

Zobrazit více v PubMed

Bragin A, Engel J, Jr, Wilson CL, Fried I, Buzsáki G. High-frequency oscillations in human brain. Hippocampus. 1999;9:137–142. doi: 10.1002/(SICI)1098-1063(1999)9:2<137::AID-HIPO5>3.0.CO;2-0. PubMed DOI

Worrell GA, et al. High-frequency oscillations and seizure generation in neocortical epilepsy. Brain. 2004;127:1496–1550. doi: 10.1093/brain/awh149. PubMed DOI

Worrell G, Gotman J. High-frequency oscillations and other electrophysiological biomarkers of epilepsy: clinical studies. Biomark. Med. 2011;5:557–566. doi: 10.2217/bmm.11.74. PubMed DOI PMC

Urrestarazu E, Chander R, Dubeau F, Gotman J. Interictal high-frequency oscillations (100–500 Hz) in the intracerebral EEG of epileptic patients. Brain. 2007;130:2354–2366. doi: 10.1093/brain/awm149. PubMed DOI

Bagshaw AP, Jacobs J, LeVan P, Dubeau F, Gotman J. Effect of sleep stage on interictal high-frequency oscillations recorded from depth macroelectrodes in patients with focal epilepsy. Epilepsia. 2009;50:617–628. doi: 10.1111/j.1528-1167.2008.01784.x. PubMed DOI PMC

Engel J, Jr, Bragin A, Staba R, Mody I. High-frequency oscillations: What is normal and what is not? Epilepsia. 2009;50:598–604. doi: 10.1111/j.1528-1167.2008.01917.x. PubMed DOI

Brázdil M, et al. Interictal high-frequency oscillations indicate seizure onset zone in patients with focal cortical dysplasia. Epilepsy Res. 2010;90:28–32. doi: 10.1016/j.eplepsyres.2010.03.003. PubMed DOI

Brázdil M, et al. Impact of cognitive stimulation on ripples within human epileptic and non-epileptic hippocampus. BMC Neurosci. 2015;16:47. doi: 10.1186/s12868-015-0184-0. PubMed DOI PMC

Brázdil M, et al. Very high-frequency oscillations: Novel biomarkers of the epileptogenic zone. Ann. Neurol. 2017;82:299–310. doi: 10.1002/ana.25006. PubMed DOI

Jacobs J, et al. High-frequency oscillations (HFOs) in clinical epilepsy. Prog. Neurobiol. 2012;98:302–315. doi: 10.1016/j.pneurobio.2012.03.001. PubMed DOI PMC

Usui N, et al. Significance of very-high-frequency oscillations (over 1,000 Hz) in epilepsy. Ann. Neurol. 2015;78:295–302. doi: 10.1002/ana.24440. PubMed DOI

Roehri N, et al. High-frequency oscillations are not better biomarkers of epileptogenic tissues than spikes. Ann. Neurol. 2018;83:84–97. doi: 10.1002/ana.25124. PubMed DOI

Engel J, Jr, da Silva FL. High-frequency oscillations—Where we are and where we need to go. Prog. Neurobiol. 2012;98:316–318. doi: 10.1016/j.pneurobio.2012.02.001. PubMed DOI PMC

Buzsáki G, Horváth Z, Urioste R, Hetke J, Wise K. High-frequency network oscillation in the hippocampus. Science. 1992;256:1025–1027. doi: 10.1126/science.1589772. PubMed DOI

Bragin A, Benassi SK, Kheiri F, Engel J., Jr Further evidence that pathologic high-frequency oscillations are bursts of population spikes derived from recordings of identified cells in dentate gyrus. Epilepsia. 2011;52:45–52. doi: 10.1111/j.1528-1167.2010.02896.x. PubMed DOI PMC

Jiruska P, et al. Synchronization and desynchronization in epilepsy: Controversies and hypotheses. J. Physiol. 2013;591:787–797. doi: 10.1113/jphysiol.2012.239590. PubMed DOI PMC

Jiruska P, et al. Update on the mechanisms and roles of high-frequency oscillations in seizures and epileptic disorders. Epilepsia. 2017;58:1330–1339. doi: 10.1111/epi.13830. PubMed DOI PMC

Jacobs J, et al. Interictal high-frequency oscillations (80–500 Hz) are an indicator of seizure onset areas independent of spikes in the human epileptic brain. Epilepsia. 2008;49:1893–1907. doi: 10.1111/j.1528-1167.2008.01656.x. PubMed DOI PMC

Bartolomei F, et al. What is the concor-dance between the seizure onset zone and the irritative zone? A SEEG quantified study. Clin. Neurophysiol. 2016;127:1157–1162. doi: 10.1016/j.clinph.2015.10.029. PubMed DOI

Buzsáki G, Silva FL. High frequency oscillations in the intact brain. Prog. Neurobiol. 2012;98:241–249. doi: 10.1016/j.pneurobio.2012.02.004. PubMed DOI PMC

Kucewicz MT, et al. High frequency oscillations are associated with cognitive processing in human recognition memory. Brain. 2014;137:2231–2244. doi: 10.1093/brain/awu149. PubMed DOI PMC

Alkawadri R, et al. The spatial and signal characteristics of physiologic high frequency oscillations. Epilepsia. 2014;55:1986–1995. doi: 10.1111/epi.12851. PubMed DOI PMC

Nagasawa T, et al. Spontaneous and visually driven high-frequency oscillations in the occipital cortex: Intracranial recording in epileptic patients. Hum. Brain Mapp. 2012;33:569–583. doi: 10.1002/hbm.21233. PubMed DOI PMC

Matsumoto A, et al. Pathological and physiological high-frequency oscillations in focal human epilepsy. J. Neurophysiol. 2013;110:1958–1964. doi: 10.1152/jn.00341.2013. PubMed DOI PMC

Pail M, et al. Frequency-independent characteristics of high-frequency oscillations in epileptic and non-epileptic regions. Clin. Neurophysiol. 2017;128:106–114. doi: 10.1016/j.clinph.2016.10.011. PubMed DOI

Wang S, et al. Ripple classification helps to localize the seizure-onset zone in neocortical epilepsy. Epilepsia. 2013;54:370–376. doi: 10.1111/j.1528-1167.2012.03721.x. PubMed DOI

Zijlmans M, et al. How to record high-frequency oscillations in epilepsy: A practical guideline. Epilepsia. 2017;58:1305–1315. doi: 10.1111/epi.13814. PubMed DOI

Jiruska P, Bragin A. High-frequency activity in experimental and clinical epileptic foci. Epilepsy Res. 2011;97:300–307. doi: 10.1016/j.eplepsyres.2011.09.023. PubMed DOI PMC

Crépon B, et al. Mapping interictal oscillations greater than 200 Hz recorded with intracranial macroelectrodes in human epilepsy. Brain. 2010;133:33–45. doi: 10.1093/brain/awp277. PubMed DOI

von Ellenrieder N, Frauscher B, Dubeau F, Gotman J. Interaction with slow waves during sleep improves discrimination of physiologic and pathologic high-frequency oscillations (80–500 Hz) Epilepsia. 2016;57:869–878. doi: 10.1111/epi.13380. PubMed DOI

Bruder JC, et al. Physiological ripples associated with sleep spindles differ in waveform morphology from epileptic ripples. Int. J. Neural. Syst. 2017;27:1750011. doi: 10.1142/S0129065717500113. PubMed DOI

Sakuraba R, et al. High frequency oscillations are less frequent but more specific to epileptogenicity during rapid eye movement sleep. Clin. Neurophysiol. 2016;127:179–186. doi: 10.1016/j.clinph.2015.05.019. PubMed DOI

Malinowska U, Bergey GK, Harezlak J, Jouny CC. Identification of seizure onset zone and preictal state based on characteristics of high frequency oscillations. Clin. Neurophysiol. 2015;126:1505–1513. doi: 10.1016/j.clinph.2014.11.007. PubMed DOI

Waldert S, Lemon RN, Kraskov A. Influence of spiking activity on cortical local filed potentials. J. Physiol. 2013;591:5291–5303. doi: 10.1113/jphysiol.2013.258228. PubMed DOI PMC

Kucewicz MT, et al. Dissecting gamma frequency activity during human memory processing. Brain. 2017;140:1337–1350. doi: 10.1093/brain/awx043. PubMed DOI

Cimbalnik J, Kucewicz MT, Worrell G. Interictal high-frequency oscillations in focal human epilepsy. Curr. Opin. Neurol. 2016;29:175–181. doi: 10.1097/WCO.0000000000000302. PubMed DOI PMC

Talairach J. Atlas d´anatomie stéréotaxique du telencéphale: etudes anatomo-radiologiques. Paris: Masson; 1967.

Barkmeier DT, et al. High inter-reviewer variability of spike detection on intracranial EEG addressed by an automated multi-channel algorithm. Clin. Neurophysiol. 2012;123:1088–1095. doi: 10.1016/j.clinph.2011.09.023. PubMed DOI PMC

Jacobs J, et al. High frequency oscillations in intracranial EEGs mark epileptogenicity rather than lesion type. Brain. 2009;132:1022–1037. doi: 10.1093/brain/awn351. PubMed DOI PMC

Andrade-Valença L, et al. Interictal high frequency oscillations (HFOs) in patients with focal epilepsy and normal MRI. Clin. Neurophysiol. 2012;123:100–105. doi: 10.1016/j.clinph.2011.06.004. PubMed DOI PMC

Axmacher N, Elger CE, Fell J. Ripples in the medial temporal lobe are relevant for human memory consolidation. Brain. 2008;131:1806–1817. doi: 10.1093/brain/awn103. PubMed DOI

Carr MF, Jadhav SP, Frank LM. Hippocampal replay in the awake state: A potential substrate for memory consolidation and retrieval. Nat. Neurosci. 2011;14:147–153. doi: 10.1038/nn.2732. PubMed DOI PMC

Girardeau G, Benchenane K, Wiener SI, Buzsáki G, Zugaro MB. Selective suppression of hippocampal ripples impairs spatial memory. Nat. Neurosci. 2009;12:1222–1223. doi: 10.1038/nn.2384. PubMed DOI

Lachaux JP, Axmacher N, Mormann F, Halgren E, Crone NE. High-frequency neural activity and human cognition: Past, present and possible future of intracranial EEG research. Prog. Neurobiol. 2012;98:279–301. doi: 10.1016/j.pneurobio.2012.06.008. PubMed DOI PMC

Steriade M, Contreras D, Amzica F. Synchronized sleep oscillations and their paroxysmal developments. Trends Neurosci. 1994;17:199–208. doi: 10.1016/0166-2236(94)90104-X. PubMed DOI

Dinner DS. Effect of sleep on epilepsy. J. Clin. Neurophysiol. 2002;19:504–513. doi: 10.1097/00004691-200212000-00003. PubMed DOI

de Guzman PH, Nazer F, Dickson CT. Short-duration epileptic discharges show a distinct phase preference during ongoing hippocampal slow oscillations. J. Neurophysiol. 2010;104:2194–2202. doi: 10.1152/jn.00418.2010. PubMed DOI

Staba RJ, Wilson CL, Bragin A, Fried I, Engel J., Jr Quantitative analysis of high-frequency oscillations (80–500 Hz) recorded in human epileptic hippocampus and entorhinal cortex. J. Neurophysiol. 2002;88:1743–1752. doi: 10.1152/jn.2002.88.4.1743. PubMed DOI

Polich J. Updating p300: An integrative theory of P3a and P3b. Clin. Neurophysiol. 2007;118:2128–2148. doi: 10.1016/j.clinph.2007.04.019. PubMed DOI PMC

Pail M, et al. Connectivity of superior temporal sulcus during target detection. J. Psychophysiol. 2016;30:29–37. doi: 10.1027/0269-8803/a000151. DOI

Lachaux JP. Dynamic spectral imaging: Online and offline functional brain mapping using high-frequency activity [50–150 Hz] in SEEG. In: Lhatoo SD, Kahane P, Lüders HO, editors. Invasive Studies of the Human Epileptic Brain. Oxford: Oxford University Press; 2019. pp. 453–464.

Ewell LA, Fischer KB, Leibold C, Leutgeb S, Leutgeb JK. The impact of pathological high-frequency oscillations on hippocampal network activity in rats with chronic epilepsy. eLife. 2019;8:e42148. doi: 10.7554/eLife.42148. PubMed DOI PMC

Meador KJ, et al. Limbic evoked potentials predict site of epileptic focus. Neurology. 1987;37:494–497. doi: 10.1212/WNL.37.3.494. PubMed DOI

Puce A, Kalnins RM, Berkovic SF, Donnan GA, Bladin PF. Limbic P3 potentials, seizure localization, and surgical pathology in temporal lobe epilepsy. Ann. Neurol. 1989;26:377–385. doi: 10.1002/ana.410260311. PubMed DOI

Brázdil M, et al. Hippocampal visual P3 potential in lateralization of primary epileptogenic focus and in assessment of hippocampal memory function in temporal lobe epilepsy. Epilepsia. 1999;40(Suppl 2):261.

Lachaux JP, Rudrauf D, Kahane P. Intracranial EEG and human brain mapping. J. Physiol. Paris. 2003;97:613–628. doi: 10.1016/j.jphysparis.2004.01.018. PubMed DOI

Curio G. Linking 600-Hz “spikelike” EEG/MEG wavelets (“ς-bursts”) to cellular substrates: Concepts and caveats. J. Clin. Neurophysiol. 2000;17:377–396. doi: 10.1097/00004691-200007000-00004. PubMed DOI

Liu S, et al. Stereotyped high-frequency oscillations discriminate seizure onset zones and critical functional cortex in focal epilepsy. Brain. 2018;141:713–730. doi: 10.1093/brain/awx374. PubMed DOI PMC

Rich EL, Wallis JD. Spatiotemporal dynamics of information encoding revealed in orbitofrontal high-gamma. Nat. Commun. 2017;8:1139. doi: 10.1038/s41467-017-01253-5. PubMed DOI PMC

Bénar CG, Chauvière L, Bartolomei F, Wendling F. Pitfalls of high-pass filtering for detecting epileptic oscillations: A technical note on “false” ripples. Clin. Neurophysiol. 2010;121:301–310. doi: 10.1016/j.clinph.2009.10.019. PubMed DOI

Menendez de la Prida L, Staba RJ, Dian JA. Conundrums of high-frequency oscillations (80–800 Hz) in the epileptic brain. J. Clin. Neurophysiol. 2015;32:207–219. doi: 10.1097/WNP.0000000000000150. PubMed DOI PMC

High frequency oscillations in human memory and cognition: a neurophysiological substrate of engrams?

Weak coupling of neurons enables very high-frequency and ultra-fast oscillations through the interplay of synchronized phase shifts

Implementation of a Morphological Filter for Removing Spikes from the Epileptic Brain Signals to Improve Identification Ripples

Protocol for multicentre comparison of interictal high-frequency oscillations as a predictor of seizure freedom

Leveraging electrophysiologic correlates of word encoding to map seizure onset zone in focal epilepsy: Task-dependent changes in epileptiform activity, spectral features, and functional connectivity