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Network-wide abnormalities explain memory variability in hippocampal amnesia

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Cite this article as: eLife 2019;8:e46156 doi: 10.7554/eLife.46156

Abstract

Patients with hippocampal amnesia play a central role in memory neuroscience but the neural underpinnings of amnesia are hotly debated. We hypothesized that focal hippocampal damage is associated with changes across the extended hippocampal system and that these, rather than hippocampal atrophy per se, would explain variability in memory between patients. We assessed this hypothesis in a uniquely large cohort of patients (n=38) after autoimmune limbic encephalitis, a syndrome associated with focal structural hippocampal pathology. These patients showed impaired recall, recognition and maintenance of new information, and remote autobiographical amnesia. Besides hippocampal atrophy, we observed correlatively reduced thalamic and entorhinal cortical volume, resting-state inter-hippocampal connectivity and activity in posteromedial cortex. Associations of hippocampal volume with recall, recognition, and remote memory were fully mediated by wider network abnormalities, and were only direct in forgetting. Network abnormalities may explain the variability across studies of amnesia and speak to debates in memory neuroscience.

Data availability

A source data file has been provided for the plots in Figure 2- figure supplement 1, and main figures 3-8. The participants of our study had not been asked to consent for their anonymized data to be publicly shared and be made freely available. Therefore, these data are available through a request to Dr Georgios Argyropoulos and would need to be approved by an ethics committee. Information relating to the 32 MRI datasets previously collected and made available via the Oxford Project To Investigate Memory and Aging can be found here https://www.ndcn.ox.ac.uk/research/centre-prevention-stroke-dementia/resources/optima-oxford-project-to-investigate-memory-and-ageing and requests to access made to Dr. Christopher Butler.

Article and author information

Author details

  1. Georgios P D Argyropoulos

    Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    For correspondence
    georgios.argyropoulos@ndcn.ox.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8267-6861
  2. Clare Loane

    Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  3. Adriana Roca-Fernandez

    Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  4. Carmen Lage-Martinez

    Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  5. Oana Gurau

    Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  6. Sarosh R Irani

    Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    Sarosh R Irani, is a coapplicant and receives royalties on patent application WO/2010/046716 (U.K. patent no., PCT/GB2009/051441) entitled 'Neurological Autoimmune Disorders'. The patent has been licensed to Euroimmun AG for the development of assays for LGI1 and other VGKC-complex antibodies..
  7. Christopher R Butler

    Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.

Funding

Medical Research Council (MR/K010395/1)

  • Christopher R Butler

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: All participants provided written informed consent according to the Declaration of Helsinki. Ethical approval was received from South Central Oxford Research Ethics Committee (REC no: 08/H0606/133).

Reviewing Editor

  1. Laura L Colgin, University of Texas at Austin, United States

Publication history

  1. Received: February 16, 2019
  2. Accepted: July 5, 2019
  3. Accepted Manuscript published: July 8, 2019 (version 1)
  4. Version of Record published: July 18, 2019 (version 2)

Copyright

© 2019, Argyropoulos et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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