Phase-Specific Hippocampal and Cortical Medial Temporal Lobe Involvement in Allocentric Working Memory

The hippocampus and cortices of the medial temporal lobe (MTL) regions are increasingly implicated in working memory, but their precise contributions--particularly during delay maintenance--remain debated. Using functional magnetic resonance imaging (fMRI), we investigated the involvement of hippocampal and cortical MTL in a demanding allocentric working memory task requiring relational binding. A total of 128 healthy human adults (92 females) aged 20-83 (mean 39) years performed an allocentric working memory task during fMRI, in which object-location bindings had to be learned, maintained, and manipulated across an 8 second delay. The design included a staircase procedure to balance task difficulty across participants and a passive viewing condition to control for perceptual and attentional demands. Across the full sample, anterior and mid hippocampal subregions and cortical MTL areas were engaged in all phases, showing study-related activation, widespread delay-phase deactivation with region-specific sustained responses, and posterior hippocampal and cortical MTL reactivation during test. Contrary to predictions, hippocampal and cortical MTL activation did not vary with performance among younger adults. Instead, differences emerged in a left temporoparietal cluster, potentially reflecting verbal encoding strategies. Older adults, relative to younger adults with the most comparable performance levels, showed lower anterior hippocampal activation and smaller correct-passive viewing differences in perirhinal and parahippocampal cortices. Taken together, these findings accord with hippocampal subregions and cortical MTL involvement across the temporal unfolding of allocentric working memory, but with distinct phase-specific roles.