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.
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.
- Christopher R Butler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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).
- Laura L Colgin, University of Texas at Austin, United States
© 2019, Argyropoulos et al.
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