Human hippocampal CA3 damage disrupts both recent and remote episodic memories

Author:

Miller Thomas D12,Chong Trevor T-J3ORCID,Aimola Davies Anne M45,Johnson Michael R6,Irani Sarosh R1,Husain Masud14,Ng Tammy WC7,Jacob Saiju8,Maddison Paul9,Kennard Christopher1,Gowland Penny A10,Rosenthal Clive R1ORCID

Affiliation:

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

2. Department of Neurology, Royal Free Hospital, London, United Kingdom

3. Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Clayton, Australia

4. Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom

5. Research School of Psychology, Australian National University, Canberra, Australia

6. Division of Brain Sciences, Imperial College London, London, United Kingdom

7. Department of Anaesthestics, Royal Free Hospital, London, United Kingdom

8. Neurology Department, Queen Elizabeth Neuroscience Centre, University Hospitals of Birmingham, Birmingham, United Kingdom

9. Neurology Department, Queen’s Medical Centre, Nottingham, United Kingdom

10. Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, United Kingdom

Abstract

Neocortical-hippocampal interactions support new episodic (event) memories, but there is conflicting evidence about the dependence of remote episodic memories on the hippocampus. In line with systems consolidation and computational theories of episodic memory, evidence from model organisms suggests that the cornu ammonis 3 (CA3) hippocampal subfield supports recent, but not remote, episodic retrieval. In this study, we demonstrated that recent and remote memories were susceptible to a loss of episodic detail in human participants with focal bilateral damage to CA3. Graph theoretic analyses of 7.0-Tesla resting-state fMRI data revealed that CA3 damage disrupted functional integration across the medial temporal lobe (MTL) subsystem of the default network. The loss of functional integration in MTL subsystem regions was predictive of autobiographical episodic retrieval performance. We conclude that human CA3 is necessary for the retrieval of episodic memories long after their initial acquisition and functional integration of the default network is important for autobiographical episodic memory performance.

Funder

Medical Research Council

Engineering and Physical Sciences Research Council

John Fell Fund, University of Oxford

National Institute for Health Research

Guarantors of Brain

Patrick Berthoud Charitable Trust

Encephalitis Society

National Health and Medical Research Council

Australian Research Council

Wellcome Trust

British Medical Association

Publisher

eLife Sciences Publications, Ltd

Subject

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

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