In vivo laminar electrophysiology co-registered with histology in the hippocampus of patients with temporal lobe epilepsy Istva ´n Ulbert, a,b, * Zso ´fia Maglo ´czky, c Lora ´nd Ero VV ss, d Sa ´ndor Czirja ´k, e Ja ´nos Vajda, e La ´szlo ´ Bogna ´r, e Szabolcs To ´th, d Zerind Szabo ´, d Pe ´ter Hala ´sz, f Da ´niel Fabo ´, f Eric Halgren, b,g Tama ´s F. Freund, c and George Karmos a a Institute for Psychology of the Hungarian Academy of Sciences, Budapest 1068, Hungary b Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Medical School, Charlestown, MA 02129, USA c Institute of Experimental Medicine of the Hungarian Academy of Sciences, Budapest 1450, Hungary d Department of Neurosurgery, MA ´ V Hospital, Budapest 1062, Hungary e National Institute for Neurosurgery, Budapest 1577, Hungary f National Institute of Psychiatry and Neurology, Epilepsy Center, Budapest 1021, Hungary g INSERM, Marseilles, France Received 27 August 2003; revised 4 December 2003; accepted 8 December 2003 Available online 10 February 2004 Abstract Laminar multiple microelectrodes have been developed to sample cortical and hippocampal activity in animals. If these measurements are adequately co-registered with the anatomy of the region, they can yield important information about its function and structure. In vivo laminar electrophysiological recordings from the human epileptic hippocampus are rare. However, histological and immunohistochemical analyses are widely used to determine the structural changes associated with temporal lobe epilepsy (TLE). Here we present data obtained by a combined approach: intraoperative recording of laminar field potentials, single and multiple unit activity under anesthesia, accompanied by histology and immunohistochemistry from the same hippocampal region of epileptic patients undergoing temporal lobectomy for drug- resistant TLE. The stability of the electrophysiology and the accuracy of its co-registration with histology were tested successfully. We have found large field potential spikes associated with bursting single units in CA1. Intracortical and subdural strip recordings from the lateral temporal cortex showed similar field potential activation patterns. A prominent oscillatory activity was present in the dentate gyrus with highly localized field potential gradient and multiple unit activity. This pattern could be used as a landmark defining the position of the electrode in the hippocampus. Our findings indicate that some aspects of the local and network epileptiform activity in the hippocampal formation are likely preserved under anesthesia. Electrophysiological identification of the functional state of the hippocampus together with its local structural correlates could further enhance our understanding of this disease. D 2004 Elsevier Inc. All rights reserved. Keywords: Temporal lobe epilepsy; Hippocampus; Human; Laminar electrophysiology; Histology; CA1; DG; Interictal spike; Bursting unit Introduction Temporal lobe epilepsy (TLE) is a devastating disease, causing cognitive impairment and decreased quality of life. The hippocampus plays a central role in the generation and maintenance of the paroxysmal activity in TLE. Numerous morphological and in vivo electrophysiological studies have assessed the structural and functional disturbances in the human hippocampus caused by TLE; however, these studies lack accurate co-registration of histology and electrophysi- ology. We believe that co-registration of the in vivo func- tional and morphological findings is a very important issue to elucidate the anatomical sources and network bases of 0014-4886/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.expneurol.2003.12.003 * Corresponding author. Department of Psychophysiology, Institute for Psychology of the Hungarian Academy of Sciences, Szondi u. 83-85, Budapest 1068, Hungary. Fax: +36-1-354-2416. E-mail address: ulbert@cogpsyphy.hu (I. Ulbert). www.elsevier.com/locate/yexnr Experimental Neurology 187 (2004) 310 – 318