- Human epilepsy LabInvestigating the cellular and network synchronisation mechanisms of the human neocortex in epileptic and non-epileptic (tumour) patients using both in vivo and postoperative in vitro electrophysiology, two-photon imaging and anatomy
Epilepsy is one of the most common neurological disorders, and is thought to be associated with neuronal hypersynchrony, resulting in the generation and maintenance of interictal activity and seizures. Our group – in collaboration with the National Institute of Clinical Neuroscience (Országos Klinikai Idegsebészeti Intézet) – uses a complex approach to investigate the cellular and network mechanisms of physiological and pathological (epileptic) synchronies. Our aim is to get insights into the cellular and network mechanisms of synchrony generation in the human neocortex. We examine how excitatory and inhibitory cells participate in the initiation of synchronous processes in epileptic patients as well as in tumour patients without epilepsy. We intend to reveal abnormalities in macro- and microcircuits in the human cortical tissue that might be causally related to seizure activity, using two photon imaging, simultaneous intracellular and multiple extracellular electrophysiology and correlated light- and electron microscopy.
We perform chronic intracortical recordings in epileptic patients with the aid of “thumbtack” electrodes inserted together with the clinical subdural electrodes, as well as intraoperative ECoG recordings from both epileptic and non-epileptic patients. Furthermore, we record neuronal activity from postoperative neocortical tissue using two-photon imaging, simultaneous intra- and extracellular electrophysiology, completed with anatomical examinations. Cellular features and behaviours characteristic to human neurons are revealed by combined two-photon imaging and intracellular patch clamp recording. Our linear multiple channel microelectrode helps us to locate the transmembrane currents along the different layers of the human neocortex, as well as to identify the discharge pattern of excitatory and inhibitory single cells. Correlated light- and electron microscopy is used to examine synaptic reorganisation and changes in the axonal connectivity of the neocortex associated to epileptic processes.
Our studies intend to clarify the subtle border between physiological and pathological processes, and perhaps suggest new targets for pharmaceutical research. Upcoming therapeutic strategies considering current human research highlights could eventuate in the development of new, more efficient approaches to prevent epileptic seizures and/or to treat the epilepsy caused damage.
Members
- Lucia Wittner, DSc (Full professor, group leader)
- István Ulbert, MD, DSc (Full professor, head of the lab)
- Kinga Tóth, PhD (Research associate)
- Ágnes Kandrács, PhD (Research associate)
- Domokos Meszéna, PhD (Research associate)
- Estilla Zsófia Tóth, PhD (Research associate)
- Bod Réka, MD (PhD student)
In collaboration with neurosurgeons (OKITI, Budapest, HU)
Lab Facilities
- In vitro setup (linear multiple channel microelectrode + sharp intracellular)
- Leica Vibratome 1000S + 1200 VT
- Two-photon laser scanning microscope (Femtonics/Olympus)
- Coherent Chameleon Ultra II femtosecond pulse lasers (galvo and resonant)
- Leica light microscope with fluorescence
- Jeol electron microscope (external, at University of Veterinary Medicine, Budapest)
Team publications
Selected publications
Please visit our Publications page for the full list.
- Kandrács Á, Hofer KT, Tóth K, Tóth EZ, Entz L, Bagó AG, Erőss L, Jordán Z, Nagy G, Fabó D, Ulbert I, Wittner L. (2019) Presence of synchrony-generating hubs in the human epileptic neocortex. J Physiol. 2019 Sep 15. doi: 10.1113/JP278499. [Epub ahead of print]
- Hagler DJ Jr, Ulbert I, Wittner L, Erőss L, Madsen JR, Devinsky O, Doyle W, Fabó D, Cash SS, Halgren E. (2018) Heterogeneous Origins of Human Sleep Spindles in Different Cortical Layers. J Neurosci. 2018 Mar 21;38(12):3013-3025. doi: 10.1523/JNEUROSCI.2241-17.2018. Epub 2018 Feb 15. (IF in 2017:5.97)
- Tóth K, Hofer KT, Kandrács A, Entz L, Bagó A, Erőss L, Jordán Z, Nagy G, Sólyom A, Fabó D, Ulbert I, Wittner L. Hyperexcitability of the network contributes to synchronization processes in the human epileptic neocortex. (2018) J Physiol (London) 2018 Jan 15;596(2):317-342. doi: 10.1113/JP275413. Epub 2017 Dec 28. (IF in 2017: 4.54), Q1
- Wittner L and Maglóczky Z (2017) Synaptic Reorganization of the Perisomatic Inhibitory Network in Hippocampi of Temporal Lobe Epileptic Patients. BioMed Research International Volume 2017, Article ID 7154295, 13 pages https://doi.org/10.1155/2017/7154295
- Kerekes BP, Tóth K, Kaszás A, Chiovini B, Szadai Z, Szalay G, Pálfi D, Bagó A, Spitzer K, Rózsa B, Ulbert I, Wittner L. (2014) Combined two-photon imaging, electrophysiological, and anatomical investigation of the human neocortex in vitro. Neurophotonics. 2014 Jul;1(1):011013. doi: 10.1117/1.NPh.1.1.011013.
Full publication history
(RCNS ICNP in collaboration with NICN neurosurgeons)- Rosen BQ, Krishnan GP, Sanda P, Komarov M, Sejnowski T, Rulkov N, Ulbert I, Eross L, Madsen J, Devinsky O, Doyle W, Fabó D, Cash S, Bazhenov M, Halgren E. (2019) Simulating human sleep spindle MEG and EEG from ion channel and circuit level dynamics. J Neurosci Methods. 2019 Mar 15;316:46-57. doi: 10.1016/j.jneumeth.2018.10.002. Epub 2018 Oct 6.
- Sampson AL, Lainscsek C, Gonzalez CE, Ulbert I, Devinsky O, Fabó D, Madsen JR, Halgren E, Cash SS, Sejnowski TJ. (2019) Delay differential analysis for dynamical sleep spindle detection. J Neurosci Methods. 2019 Mar 15;316:12-21. doi: 10.1016/j.jneumeth.2019.01.009. Epub 2019 Jan 30.
- Kandrács Á, Hofer KT, Tóth K, Tóth EZ, Entz L, Bagó AG, Erőss L, Jordán Z, Nagy G, Fabó D, Ulbert I, Wittner L. (2019) Presence of synchrony-generating hubs in the human epileptic neocortex. J Physiol. 2019 Sep 15. doi: 10.1113/JP278499. [Epub ahead of print]
- Hagler DJ Jr, Ulbert I, Wittner L, Erőss L, Madsen JR, Devinsky O, Doyle W, Fabó D, Cash SS, Halgren E. (2018) Heterogeneous Origins of Human Sleep Spindles in Different Cortical Layers. J Neurosci. 2018 Mar 21;38(12):3013-3025. doi: 10.1523/JNEUROSCI.2241-17.2018. Epub 2018 Feb 15.
- Halgren M, Fabó D, Ulbert I, Madsen JR, Erőss L, Doyle WK, Devinsky O, Schomer D, Cash SS, Halgren E. (2018) Superficial Slow Rhythms Integrate Cortical Processing in Humans. Sci Rep. 2018 Feb 1;8(1):2055. doi: 10.1038/s41598-018-20662-0.
- Tóth K, Hofer KT, Kandrács Á, Entz L, Bagó A, Erőss L, Jordán Z, Nagy G, Sólyom A, Fabó D, Ulbert I, Wittner L. (2017) Hyperexcitability of the network contributes to synchronization processes in the human epileptic neocortex. J Physiol. 2017 Nov 27. doi: 10.1113/JP275413.
- Wittner L and Maglóczky Z (2017) Synaptic Reorganization of the Perisomatic Inhibitory Network in Hippocampi of Temporal Lobe Epileptic Patients. BioMed Research International Volume 2017, Article ID 7154295, 13 pages https://doi.org/10.1155/2017/7154295
- Karlócai MR, Wittner L, Tóth K, Maglóczky Z, Katarova Z, Rásonyi G, Erőss L, Czirják S, Halász P, Szabó G, Payne JA, Kaila K, Freund TF. (2016) Enhanced expression of potassium-chloride cotransporter KCC2 in human temporal lobe epilepsy. Brain Struct Funct. 2016 Sep;221(7):3601-15. doi: 10.1007/s00429-015-1122-8.
- Tóth E, Fabó D, Entz L, Ulbert I, Erőss L. (2016) Intracranial neuronal ensemble recordings and analysis in epilepsy. J Neurosci Methods. 2016 Feb 15;260:261-9. doi: 10.1016/j.jneumeth.2015.09.028. Review.
- Kerekes BP, Tóth K, Kaszás A, Chiovini B, Szadai Z, Szalay G, Pálfi D, Bagó A, Spitzer K, Rózsa B, Ulbert I, Wittner L. (2014) Combined two-photon imaging, electrophysiological, and anatomical investigation of the human neocortex in vitro. Neurophotonics. 2014 Jul;1(1):011013. doi: 10.1117/1.NPh.1.1.011013.
- Tóth K, Maglóczky Z. (2014) The vulnerability of calretinin-containing hippocampal interneurons to temporal lobe epilepsy. Front Neuroanat. 2014 Sep 29;8:100. doi: 10.3389/fnana.2014.00100. Review.
- Entz L, Tóth E, Keller CJ, Bickel S, Groppe DM, Fabó D, Kozák LR, Erőss L, Ulbert I, Mehta AD. (2014) Evoked effective connectivity of the human neocortex. Hum Brain Mapp. 2014 Dec;35(12):5736-53. doi: 10.1002/hbm.22581.
- Ludányi A, Hu SS, Yamazaki M, Tanimura A, Piomelli D, Watanabe M, Kano M, Sakimura K, Maglóczky Z, Mackie K, Freund TF, Katona I. (2011) Complementary synaptic distribution of enzymes responsible for synthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in the human hippocampus. Neuroscience. 2011 Feb 3;174:50-63.
- Hangya B, Tihanyi BT, Entz L, Fabó D, Erőss L, Wittner L, Jakus R, Varga V, Freund TF, Ulbert I (2011) Complex Propagation Patterns Characterize Human Cortical Activity during Slow-Wave Sleep. J Neurosci. 2011 Jun 15;31(24):8770-9. (IF: 7.115)
- Maglóczky Z. (2010) Sprouting in human temporal lobe epilepsy: excitatory pathways and axons of interneurons. Epilepsy Res. 2010 Mar;89(1):52-9.
- Maglóczky Z, Tóth K, Karlócai R, Nagy S, Eross L, Czirják S, Vajda J, Rásonyi G, Kelemen A, Juhos V, Halász P, Mackie K, Freund TF. (2010) Dynamic changes of CB1-receptor expression in hippocampi of epileptic mice and humans. Epilepsia. 2010 Jul;51 Suppl 3:115-20.
- Tóth K, Erőss L, Vajda J, Halász P, Freund TF, Maglóczky Z. (2010) Loss and reorganization of calretinin-containing interneurons in the epileptic human hippocampus. Brain. 2010 Sep;133(9):2763-77.
- Csercsa R, Dombovári B, Fabó D, Wittner L, Erőss L, Entz L, Sólyom A, Rásonyi G, Szűcs A, Kelemen A, Jakus R, Juhos V, Grand L, Magony A, Halász P, Freund TF, Maglóczky Z, Cash SS, Papp L, Karmos G, Halgren E, Ulbert I. (2010) Laminar analysis of slow wave activity in humans. Brain. 2010 Sep;133(9):2814-29. (IF: 9.232)
- Wittner L, Huberfeld G, Clémenceau S, Erőss L, Dezamis E, Entz L, Ulbert I, Baulac M, Freund TF, Maglóczky Z, Miles R. (2009) The epileptic human hippocampal cornu ammonis 2 region generates spontaneous interictal-like activity in vitro. Brain. 2009 Nov;132(Pt 11):3032-46. (IF: 9.49)
- Cash SS, Halgren E, Dehghani N, Rossetti AO, Thesen T, Wang C, Devinsky O, Kuzniecky R, Doyle W, Madsen JR, Bromfield E, Erőss L, Halász P, Karmos G, Csercsa R, Wittner L, Ulbert I. (2009) The human K-complex represents an isolated cortical down-state. Science. 2009 May 22;324(5930):1084-7. (IF: 29.747)
- Erőss L, Entz L, Fabó D, Jakus R, Szűcs A, Rásonyi G, Kelemen A, Barcs G, Juhos V, Balogh A, Barsi P, Clemens Z, Halász P. (2009) Interhemispheric propagation of seizures in mesial temporal lobe epilepsy. Ideggyogy Sz. 2009 Sep 30;62(9-10):319-25.
- Ludányi A, Erőss L, Czirják S, Vajda J, Halász P, Watanabe M, Palkovits M, Maglóczky Z, Freund TF, Katona I. (2008) Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. J Neurosci. 2008 Mar 19;28(12):2976-90.
- D. Fabó, Zs. Maglóczky, L. Wittner, Á. Pék, L. Erőss, S. Czirják, J. Vajda, A. Sólyom, G. Rásonyi, A. Szűcs, A. Kelemen, V. Juhos, L. Grand, B. Dombovári, P. Halász, T. F. Freund, E. Halgren, Gy. Karmos, I. Ulbert (2008) Properties of in vivo interictal spike generation in the human subiculum. Brain. 2008 Feb;131(Pt 2):485-99. (IF: 9.603)
- K. Tóth, L. Wittner, Z. Urbán, W. K. Doyle, Gy. Buzsáki, R. Shigemoto, T. F. Freund and Zs. Maglóczky (2007) Morphology and synaptic input of substance P receptor-immunoreactive interneurons in control and epileptic human hippocampus. Neuroscience 144 (2): 495-508. (IF: 3.352)
- Maglóczky Z, Freund TF. (2005) Impaired and repaired inhibitory circuits in the epileptic human hippocampus. Trends Neurosci. 2005 Jun;28(6):334-40. Review.
- Clemens Z, Janszky J, Clemens B, Szűcs A, Halász P. (2005) Factors affecting spiking related to sleep and wake states in temporal lobe epilepsy (TLE). Seizure. 2005 Jan;14(1):52-7.
- L. Wittner, L. Erőss, S. Czirják, P. Halász, T. F. Freund and Zs. Maglóczky (2005) Surviving CA1 pyramidal cells receive intact perisomatic inhibitory input in the human epileptic hippocampus. Brain 128:138-152 (IF: 7.535)
- Ulbert I, Maglóczky Z, Erőss L, Czirják S, Vajda J, Bognár L, Tóth S, Szabó Z, Halász P, Fabó D, Halgren E, Freund TF, Karmos G. (2004) In vivo laminar electrophysiology co-registered with histology in the hippocampus of patients with temporal lobe epilepsy. Exp Neurol. 2004 Jun;187(2):310-8.
- L. Wittner, L. Erőss, Z. Szabó, Sz. Tóth, S. Czirják, P. Halász, T.F. Freund and Zs. Maglóczky (2002) Synaptic reorganization of calbindin-positive neurons in the human hippocampal CA1 region in temporal lobe epilepsy. Neuroscience 115 (3):961-978. (IF: 3.457)
- L. Wittner, Zs. Maglóczky, Zs. Borhegyi, P. Halász, Sz. Tóth, L. Erőss, Z. Szabó and T.F. Freund (2001) Preservation of perisomatic inhibitory input of granule cells in the epileptic human dentate gyrus. Neuroscience 108 (4):587-600. (IF: 3.219)
- Maglóczky Zs., Wittner L., Borhegyi Zs., Halász P., Vajda J., Czirják S., Freund T. F. (2000) Changes in the distribution and connectivity of interneurons in the epileptic human dentate gyrus. Neuroscience 96 (1):7-25. (IF: 3.563)
- Maglóczky Z, Halász P, Vajda J, Czirják S, Freund TF. (1997) Loss of Calbindin-D28K immunoreactivity from dentate granule cells in human temporal lobe epilepsy. Neuroscience. 1997 Jan;76(2):377-85.
- Kandrács Á, Hofer KT, Tóth K, Tóth EZ, Entz L, Bagó AG, Erőss L, Jordán Z, Nagy G, Fabó D, Ulbert I, Wittner L. (2019) Presence of synchrony-generating hubs in the human epileptic neocortex. J Physiol. 2019 Sep 15. doi: 10.1113/JP278499. [Epub ahead of print]
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