Working Memory Deficits in Hippocampal Amnesia are Associated with Apathy

Abstract

The hippocampus is increasingly recognized for its role in working memory representations and goal-directed behavior, yet whether these functions share common neural substrates remains unclear. We investigated short-term memory performance in 27 patients (21 males and 6 females) with LGI1-antibody limbic encephalitis, a condition with predominant hippocampal involvement, compared to 27 age- and gender-matched healthy controls, using an object–location continuous report task with Bayesian mixture-modeling. Patients exhibited predominantly elevated misbinding errors—incorrectly associating objects with non-target locations—with unaltered guessing and only marginally reduced precision. Critically, apathy was positively associated with misbinding exclusively in patients, independent of depression and global cognition. Neuroimaging in a subset of patients (n = 12) revealed reduced hippocampal volumes and preliminary evidence for diminished hippocampal—medial prefrontal connectivity, which was associated with both higher apathy and increased misbinding at short retention intervals. These findings demonstrate that hippocampal dysfunction produces convergent deficits in memory binding and motivation, potentially reflecting disruption of a common brain mechanism linking working memory processing to goal-directed behavior.