Network-wide abnormalities explain memory variability in hippocampal amnesia.

Georgios Pd Argyropoulos,Clare Loane,Sarosh R Irani,Adriana Roca-Fernandez,Oana Gurau,Carmen Lage-Martinez,Christopher R Butler

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.

Highlights

Ever since the first report of the famous patient H.M. (Scoville and Milner, 1957), hippocampal (HPC) amnesia has played a fundamental role in the neuroscience of human memory (MacPherson and Della Sala, 2019)
Using resting-state fMRI, we identified resting-state functional abnormalities in patients with respect to both segregation and integration, that is in terms of hemodynamic activity in local regions and functional connectivity between regions
Their cognitive profile was characterized by highly focal episodic memory impairment

Summary

Introduction

Ever since the first report of the famous patient H.M. (Scoville and Milner, 1957), hippocampal (HPC) amnesia has played a fundamental role in the neuroscience of human memory (MacPherson and Della Sala, 2019). Broader network abnormalities are well documented in other ‘focal’ conditions [e.g. ischemic stroke (Carter et al, 2010; Veldsman et al, 2018)] and have been demonstrated in small case series of amnesic patients (Hayes et al, 2012; Henson et al, 2016; Rudebeck et al, 2013). These abnormalities may be important in understanding memory impairment in neurological disease (Addis et al, 2007) but their explanatory potential is underexplored.

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