RAPID COMMUNICATION Hippocampal Involvement in Retrieval of Odor vs. Object Memories Hanne Lehn, 1 * Lisa J. Kjønigsen, 1 Grete Kjelvik, 1 and Asta K. Ha ˚berg 2,3 ABSTRACT: The aim of this study was to investigate the role of the human hippocampus in episodic retrieval of odors, in comparison with episodic retrieval of visual objects. Subjects encoded a set of unique odors and objects, and retrieval was tested the next day during func- tional magnetic resonance imaging (fMRI). Subjects were shown the names of old (studied) and new (unstudied) odors and objects, and asked to indicate which of these stimuli had been presented the previ- ous day. The results showed that brain activation was weaker and more restricted during retrieval of odors than during retrieval of objects, which possibly reflects a general visual dominance effect. Yet, retrieval of odors and objects yielded overlapping clusters of activation the bilat- eral hippocampi, and the left-sided activation was specifically increased during successful retrieval (hits > correct rejections) in both modalities. Moreover, retrieval of odors uniquely activated olfactory cortical regions, likely to reflect cortical reinstatement of sensory details. Our fMRI study is the first to make a direct comparison between olfactory and visual epi- sodic memory, and the results provide clear evidence for modality-inde- pendent functions of the hippocampus. V V C 2012 Wiley Periodicals, Inc. KEY WORDS: hippocampus; episodic memory; olfactory memory; modality effects; human The hippocampus and surrounding structures in the medial temporal lobe (MTL) support the initial formation and later retrieval of episodic memories (Squire et al., 2004). Studies of amnesic patients have shown that MTL damage disrupts memory in all sensory modalities, including visual, auditory, tactile, and olfactory (Milner, 1972; Squire et al., 2001; Levy et al., 2004). However, most studies of hippocampal function in humans have focused on visual memory, and much less is known about memory in other domains. Although the MTL receives input from all sensory areas in the cortex, the strength of projections differ across ana- tomical subregions; e.g., auditory regions project most strongly to the parahippocampal cortex, whereas olfactory regions primarily target the entorhinal cortex (Suzuki and Amaral, 1994; Suzuki, 1996). These data suggest that differences may exist in the functional contributions of MTL subregions to memory in different modalities. In this study we investigate hippocampal involvement in olfactory memory using functional magnetic resonance imaging (fMRI). Olfactory memory is of interest to us since dysfunctions in this domain are associated with the early stages of Alzheimer’s disease (Nordin and Mur- phy, 1998; Devanand et al., 2000). Studying olfactory memory in humans also has a translational potential, in that odor stimuli are frequently used in paradigms that assess hippocampal functions in rodents (Eichen- baum, 1998). Human patients with hippocampal damage have impaired odor memory span (Levy et al., 2003), odor recognition performance (Levy et al., 2004), and odor-object associative memory (Goodrich-Hunsaker et al., 2009). Although early Positron-Emission-To- mography (PET) studies failed to observe hippocam- pal activation during odor recognition (Qureshy et al., 2000; Savic et al., 2000; Dade et al., 2002), a handful of fMRI-studies have also tested episodic memory with olfactory stimuli and do report hippocampal involvement. Cerf-Ducastel and Murphy (2006) meas- ured associative recognition of odors with the odor names as retrieval cues and found increased responses in the hippocampus to names of previously presented, compared to not presented, odors. More recently, Royet et al. (2011) showed that activation in the hip- pocampus is particularly increased during successful recognition, and may also depend on the level of diffi- culty and search effort. Other fMRI studies describe hippocampal involvement in odor familiarity (Plailly et al., 2007), encoding and retrieval of odor–object associations (Yeshurun et al., 2009) and odor cueing of memory retrieval (Rasch et al., 2007). In sum, the available evidence shows that the hip- pocampus is involved in episodic memory of odors, but more research is needed to describe how hippo- campal contributions to olfactory memory may differ from contributions to memory in other modalities. Very few studies have made direct cross-modal com- parisons. Levy et al. (2003) tested both visual and olfactory memory span and found that both were sim- ilarly impaired in patients with hippocampal damage. Plailly et al. (2007) reported that hippocampal activa- tion during feelings-of-familiarity was unaffected by stimulus modality, i.e., olfactory or auditory. In con- trast, Yeshurun et al. (2009) found that the hippocam- pus responded preferentially during encoding of first 1 Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; 2 Department of Medical Imaging, St. Olav’s Hospital, Trondheim, Norway; 3 Depart- ment of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway Lisa J. Kjønigsen is currently at Center for Molecular Biology and Neuroscience and Institute of Basic Medical Sciences, University of Oslo, Norway. Grant sponsor: The Norwegian Research Council; Grant number: 165334. *Correspondence to: Hanne Lehn, MR Center, St. Olav’s Hospital, Ragn- hilds gate 15, N-7030 Trondheim, Norway. E-mail: hanne.lehn@ntnu.no Accepted for publication 6 August 2012 DOI 10.1002/hipo.22073 Published online 21 September 2012 in Wiley Online Library (wileyonlinelibrary.com). HIPPOCAMPUS 23:122–128 (2013) V V C 2012 WILEY PERIODICALS, INC.