Greater hippocampal atrophy in developmental amnesia is associated with better recall and working memory performance

Abstract Despite early-life bilateral hippocampal damage, developmental amnesic (DA) patients exhibit well-developed semantic memory, but severely impaired episodic retrieval. It is unclear, however, whether the residual hippocampus plays a role in encoding and/or retrieval of new information. Here, we report that in DA patients the extent of atrophy in CA-DG subregions and subicular complex is above 40% while the atrophy of the uncus is only moderate (−23%). Importantly, the perihippocampal cortices are unaffected. Paradoxically, patients’ recall, Verbal IQ, Working Memory, and Processing Speed scores correlate negatively with the volume of the uncus. We propose that in DA patients, the uncus serves as “gatekeeper” providing signals that may inhibit compensatory mnemonic functions by the preserved surrounding cortical areas. Our findings highlight the role of uncus in recall, and document not only the extent, but also the limits of functional plasticity and circuit reorganization in the young brain after early bilateral hippocampal damage.