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Dissociating prefrontal and hippocampal function in episodic memory encoding

Nature volume 388, pages 582–585 (1997)Cite this article

Abstract

Human lesion data indicate that an intact left hippocampal formation is necessary for auditory–verbal memory1. By contrast, functional neuroimaging has highlighted the role of the left prefrontal cortex2,3,4 but has generally failed to reveal the predicted left hippocampal activation. Here we describe an experiment involving learning category–exemplar word pairs (such as ‘dog…boxer’) in which we manipulate the novelty of either individual elements or the entire category–exemplar pairing. We demonstrate both left medial temporal (including hippocampal) and left prefrontal activation and show that these activations are dissociable with respect to encoding demands. Left prefrontal activation is maximal with a change in category–exemplar pairings, whereas medial temporal activation is sensitive to the overall degree of novelty. Thus, left prefrontal cortex is sensitive to processes required to establish meaningful connections between a category and its exemplar, a process maximized when a previously formed connection is changed. Conversely, the left medial temporal activation reflects processes that register the overall novelty of the presented material. Our results provide striking evidence of functionally dissociable roles for the prefrontal cortex and hippocampal formation during learning of auditory–verbal material.

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Figure 1: The experimental design, which involved subjects hearing 12 word-paired associates while being scanned.
Figure 2: a, A statistical parametric map (SPM)29 of a comparison between the combined ‘new–old’ and ‘old–new’ and the ‘old–old’ conditions, which shows greater activation in the left dorsolateral prefrontal cortex.
Figure 3: a, An SPM of the comparison between the ‘new–new’ and the ‘old–old’ conditions, showing significantly greater activation in the former centred on the left medial temporal cortex that incorporates the left hippocampus.

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Acknowledgements

We thank our volunteers and the radiography staff at the Wellcome Department, and R. Lai for library services. R.J.D. and P.F. are supported by the Wellcome Trust.

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Authors and Affiliations

  1. Wellcome Department of Cognitive Neurology, Institute of Neurology, Queen Square, WC1N 3BG, London, UK

    R. J. Dolan & P. C. Fletcher

  2. Royal Free Hospital School of Medicine, Roland Hill Street, NW3, London, UK

    R. J. Dolan

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  1. R. J. Dolan
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  2. P. C. Fletcher
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Dolan, R., Fletcher, P. Dissociating prefrontal and hippocampal function in episodic memory encoding. Nature 388, 582–585 (1997). https://doi.org/10.1038/41561

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