Elsevier

Brain Research

Volume 1161, 3 August 2007, Pages 46-55
Brain Research

Research Report
Medial temporal lobe activations during associative memory encoding for arbitrary and semantically related object pairs

https://doi.org/10.1016/j.brainres.2007.05.046Get rights and content

Abstract

Previous positron emission tomography (PET) studies have shown greater medial temporal lobe activation (MTL) for associative memory encoding relative to deep item-oriented encoding. Greater MTL activation has also been reported for associative novelty detection. Although it has been suggested that these patterns of MTL activation could reflect the creation of novel associations into memory, it is unclear whether associative encoding and associative novelty detection rely on the same MTL substructures. In this study, we used event-related functional magnetic resonance imaging (er-fMRI) to reproduce previous reports of greater hippocampal activation for associative encoding using both arbitrary and semantically related object pairs. This paradigm allowed us to assess whether the requirement for associative processing at encoding interacts with associative novelty. Contrasting the pattern of activation for associative versus item-oriented encoding revealed greater right hippocampal activation as well as parahippocampal activation bilaterally, reproducing the findings from previous PET experiments. The orthogonal contrast between arbitrary and related pairs revealed greater activation in the left parahippocampal region, but no significant interaction between the type of encoding (associative or item oriented) and the type of pairs (arbitrary or semantically related) was observed in the medial temporal lobe (MTL). These results suggest that both associative processing and associative novelty detection can activate the MTL. Most importantly, this study suggests that associative processing can activate the MTL regardless of the pre-existence of an association between the items of a pair.

Introduction

Functional imaging studies have consistently reported the activation of the medial temporal lobes (MTL) during episodic memory encoding tasks, particularly when these tasks explicitly promote associative (or relational) encoding (Achim and Lepage, 2005b, Davachi et al., 2001, Henke et al., 1997, Henke et al., 1999, Vandenberghe et al., 1996). Associative processing and the related pattern of MTL activation during encoding have been reported to enhance episodic memory encoding and favor later the retrieval of the studied material (Davachi and Wagner, 2002, Henke et al., 1997, Henke et al., 1999, Kirwan and Stark, 2004, Woodward et al., 2006). In two seminal positron emission tomography (PET) studies, Henke et al., 1997, Henke et al., 1999 contrasted associative encoding to deep item-oriented encoding and in both experiments observed right hippocampal activation, thus providing clear evidence for a modulation of hippocampal activity as a function of associative processing. Moreover, in one of these studies (Henke et al., 1999) a shallow item-oriented encoding condition was added, leading to significant differences in hippocampal activation between associative encoding and shallow item-oriented encoding, but not between deep and shallow item-oriented encoding. This suggests that the requirement for associative processing, and not merely the depth of encoding, modulates hippocampal activity.

While these and other PET studies (see Lepage et al., 1998 for a review) have provided new insights into the role of the hippocampus in episodic memory processes, some specific methodological limitations inherent to this technique makes it necessary to reproduce and expand these important findings with designs that are better suited to examine subtle differences in processing requirements. For instance, previous PET and fMRI studies have shown partially different patterns of MTL activation during memory encoding (Schacter and Wagner, 1999). It has been suggested that the relatively low spatial resolution of PET, combined with the absence of co-registration to a structural MRI image of the participants, makes it difficult to determine the precise location of activations within MTL subregions (Henson, 2005). Furthermore, in contrast to block designs, event-related designs provide a better control over the cognitive processes involved in memory encoding, especially when these transient processes of interest are trial-specific and could potentially be confounded by state-related activation linked to attention or habituation (Constable et al., 2000, Powell et al., 2005).

The first aim of our present study was to replicate Henke et al., 1997, Henke et al., 1999 results of greater hippocampal activation for associative encoding relative to deep item-oriented encoding using a methodology that is free of the previous limitations discussed above. To that end, we used an event-related fMRI design in which subjects were presented pairs of clipart images and were prompted to encode the pairs using strategies that favored either associative or item-oriented processing.

The second objective of the present study was to determine whether the hippocampal activation reported by Henke et al. is enhanced by the novelty of the association or whether it generalizes to pairs in which a semantic relationship is already established between the items of the pair. Hippocampal activation has often been reported for conditions in which the detection of novel associations is contrasted to that of already established (i.e., previously encountered) associations (Düzel et al., 2003, Kohler et al., 2005, Pihlajamaki et al., 2004, Woodward et al., 2006). Consistent with previous results, it has been proposed that this novelty response in the hippocampus could reflect the spontaneous encoding of these new associations into memory (Kohler et al., 2005). This idea of spontaneous encoding during novelty detection is also supported by the observation that MTL activation during novelty detection is significantly correlated with subsequent recognition performance (Stark and Okado, 2003, Woodward et al., 2006).

In this study, we examined the effect of associative novelty1 detection by pairing the stimuli either arbitrarily (e.g., a shirt and a tree) or based on the pre-existence of a semantic relationship (e.g., a chicken and an egg). This manipulation allowed us to assess the main effect of associative novelty and the interaction with the type of encoding instruction. An interaction would be expected if our associative encoding instructions promoted greater associative binding for the arbitrary pairs than for related pairs. Because of our a priori hypotheses, we focused our investigation on the MTL (hippocampus and parahippocampal gyrus). For completeness, we nonetheless touch upon the pattern activation observed in other brain regions.

An item recognition test (not scanned) in which subjects had to distinguish between previously encoded and new pairs followed the encoding task, allowing to evaluate the effect of our encoding manipulations on memory retrieval. To ensure that our associative encoding task indeed promoted associative recognition, an additional behavioral study (not scanned) was also conducted in which participants performed the same encoding task followed by an associative recognition task (i.e., subjects have to distinguish between intact and rearranged pairs, see Experimental procedure and Fig. 1).

Section snippets

Behavioral results for the fMRI task

During encoding, the performance was defined as the percentage of correct answers to the encoding questions (see Experimental procedure). Both misses and incorrect responses were considered as a wrong answer. Although the encoding tasks were generally performed well, one subject performed at chance level for item-oriented encoding of arbitrary pairs. This subject was debriefed after scanning, revealing that a positive response was given only when both items were alive (in the original

Discussion

In this study, we used event-related fMRI to investigate the neural correlates of associative encoding using a manipulation of encoding instructions that either favored associative or item-oriented processing. We also examined the neural correlates of semantic associative novelty detection using a manipulation of image pair relatedness. The fact that we observed activation in different MTL regions for our two encoding manipulations and that there was no interaction in the medial temporal lobes

Subjects

Sixteen healthy participants between 18 and 32 years old (mean = 23.6; 7 males), with no lifetime history of neurological disorder, psychiatric disorder, or substance dependence, participated in this study.

Scanning procedure

Scanning was carried out at the Montreal Neurological Institute (MNI) on a 1.5-T Siemens Sonata system. The head was stabilized with a moldable vacuum cushion to minimize head movement. A T1 image was first acquired for each subject. Two fMRI blocks followed and each consisted of 214

Acknowledgments

This study was supported by CIHR (grant #68961), the Sackler Foundation, and by a CIHR studentship to A.M.A. M.L. is supported by a salary award from FRSQ. A.K. Malla is supported by the Canada Research Chairs program. We thank B. Pike, A. Cormier and the staff of the Brain Imaging Centre for their technical expertise and M. Menear for editing the manuscript.

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