Network-wide abnormalities explain memory variability in hippocampal amnesia

Author:

Argyropoulos Georgios PD1ORCID,Loane Clare12,Roca-Fernandez Adriana1,Lage-Martinez Carmen13,Gurau Oana1,Irani Sarosh R4,Butler Christopher R1ORCID

Affiliation:

1. Memory Research Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

2. Institute of Cognitive Neuroscience, University College London, London, United Kingdom

3. Valdecilla Biomedical Research Institute, University Hospital Marqués de Valdecilla, Santander, Spain

4. Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom

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.

Funder

Wellcome Trust

UCB-Oxford University Alliance

British Medical Association

Epilepsy Research UK

US-UK Fulbright Commission

Medical Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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