Human Entorhinal Gamma and Theta Oscillations Selective for Remote Autobiographical Memory Sarah Steinvorth, 1 * Chunmao Wang, 2 Istvan Ulbert, 3,4 Donald Schomer, 5 and Eric Halgren 6 ABSTRACT: Current source densities in different layers of the human entorhinal cortex (ER) were recorded using a linear array of 24 micro- electrodes during three memory conditions: a remote autobiographical condition eliciting recollections of events that occurred 10 or more years ago in the participant’s past, a semantic icon condition invoking the mental image of a well-known object, and a semantic knowledge condition asking about general information. Our data demonstrate theta, gamma, and delta oscillations in left ER particularly for remote autobiographical memory. Gamma is predominant in hippocampally projecting layers during presentation of the memory cue, whereas theta is prolonged and dominant in cortically projecting layers during memory retrieval. Gamma interactions between ER and hippocampal formation (HF) may elicit an HF contribution to recall under influences relayed from the association cortex (AC). This contribution may then be relayed back to AC during retrieval of the memory orchestrated by theta inter- actions with ER. Accordingly, theta oscillations were recorded simulta- neously in frontal and temporal cortices. V V C 2009 Wiley-Liss, Inc. KEY WORDS: remote memory; medial temporal lobes; episodic memory; consolidation; intracranial EEG INTRODUCTION Episodic recollection of one’s own past events allows one to ‘‘travel’’ back in time and re-live events from remote time periods. This form of memory engages not only recognition and recall of events from a specific time and place but the ‘‘autonoetic’’ awareness that this event belongs to one’s own personal past (Tulving, 2002). It is well known that the medial temporal lobes (MTL) are essential for the acquisition and initial retrieval of declarative memories (Milner, 1959). Stimulation of the human MTL can evoke intense reminiscences of previous events or powerful feelings of de´ja` vu (Bancaud et al., 1994). Theta oscillations (4–8 Hz) in humans are implicated in working memory (Raghavachari et al., 2001; Rizzuto et al., 2003; Meltzer et al., 2008; Payne and Kounios, 2009), episodic memory (Sederberg et al., 2007), and semantic memory (Bastiaansen et al., 2008). An increase in rhinal–hippocampal gamma (>30 Hz) and theta coherence was observed during successful memory formation in humans using depth electrodes (Fell et al., 2003). Theta oscillation in the hippocampus of animals is prominent in a range of mnemonic processes (Bastiaansen and Hagoort, 2003). In animals, theta activity has been recorded from all subfields of the hippocampus and from the entorhinal cortex (ER) (Bastiaansen and Hagoort, 2003). The ER has a pivotal position within MTL, providing the main input and output link between the hippocampal formation (HF) and association cortex (AC), crucial for declarative memory functions (Witter et al., 2000). It consists of five cortical layers with layers II and III forming the main relay of information from neocortical areas to the HF via the perforant path, and with layer V establishing the main output relaying back to the neocortex infor- mation from the subicular terminus of the hippocampal tri-synaptic pathway (Witter et al., 2000). Decline in ER volume predicts memory deterioration in mild cog- nitive impairment and dementia as well as poorer mem- ory performance in healthy subjects (Killiany et al., 2000; Rodrigue and Raz, 2004). It has been proposed that the interplay between ER and HF gamma and theta band rhythms performs a key function in the formation of declarative memories (Wallenstein and Hasselmo, 1997; Chrobak et al., 2000; Lisman and Otmakhova, 2001; Hasselmo and Brandon, 2008). Gamma and theta activities have been implicated in encoding and retrieval during working memory (Tallon-Baudry et al., 1998; Doppelmayr et al., 2000; Lisman and Otmakhova, 2001; Rizzuto, 2003; Jacobs et al., 2006; Sederberg et al., 2007). Theta oscillations have been further implicated in recall and recognition of newly learned material (Doppelmayr et al., 2000; Lisman and Otmakhova, 2001). In this case study, we examined gamma and theta oscillation in the left ER while recalling remote declarative memories. The role of MTL in remote memory is highly controversial. Some authors assume 1 Masssachusetts General Hospital/Massachusetts Institute of Technol- ogy/Harvard Medical School Martinos Center for Biomedical Imaging, Charlestown, Massachusetts; 2 National Institute on Deafness and Other Communication Disorders, National Institute of Health, Bethesda, Mary- land; 3 Institute for Psychology, Hungarian Academy of Sciences, Buda- pest, Hungary; 4 Peter Pazmany Catholic University, Department of Information Technology, Budapest, Hungary; 5 Department of Neurol- ogy, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; 6 Center for Multimodal Imaging, University of California-San Diego, La Jolla, San Diego, California Grant sponsor: NIH; Grant numbers: NS18741, NS44623 *Correspondence to: Sarah Steinvorth, Masssachusetts General Hospital/ Massachusetts Institute of Technology/Harvard Medical School Martinos Center for Biomedical Imaging, Bld. 149 13th Street, Charlestown, MA 02129, USA. E-mail: ssteinv@nmr.mgh.harvard.edu Accepted for publication 10 February 2009 DOI 10.1002/hipo.20597 Published online 31 March 2009 in Wiley InterScience (www.interscience. wiley.com). HIPPOCAMPUS 20:166–173 (2010) V V C 2009 WILEY-LISS, INC.