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

Abstract

The hippocampus and cortices of the medial temporal lobe (MTL) are increasingly implicated in working memory, particularly for tasks requiring complex, high-resolution relational binding, 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 high-resolution, relational binding. During fMRI, 128 healthy human adults (92 females) aged 20-83 (mean 39) years performed a task in which object-location bindings had to be learned, maintained, and manipulated across an 8 second delay. The design included a passive viewing condition to control for perceptual and attentional demands and a staircase procedure to balance task difficulty across participants. Across the full sample, anterior and mid hippocampal subregions and cortical MTL areas were engaged during encoding. In the delay phase, we observed a non-uniform pattern, with hippocampal and entorhinal deactivation alongside perirhinal and parahippocampal activation. During test, activation occurred in posterior hippocampus and several cortical MTL regions. 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 demonstrate distinct phase-specific hippocampal and cortical MTL involvement across the temporal unfolding of allocentric working memory, with evidence of hippocampal engagement even during the delay, yet the absence of MTL-performance associations among younger adults suggests this involvement, while robust, may play a more auxiliary role.