Distinct contributions of dissociable brain networks and hippocampal subregions to memory fidelity

A crucial function of memory is to distinguish between similar experiences. Mnemonic discrimination paradigms that require participants to tell apart targets and highly similar lures can probe a brain region’s ability to resolve such interference and form high-fidelity memories. Based on these paradigms the hippocampal subfields dentate gyrus (DG) and CA3 were previously shown to engage in pattern separation (PS), a process to orthogonalize similar stimuli to reduce overlap. Cortical regions may additionally contribute to pattern separation in a category-specific manner with some regions being specialized for objects and others for scenes.
Ultra-high resolution 7-Tesla imaging was used to identify category-specific and -invariant neural correlates of mnemonic discrimination. This method could overcome limitations of prior 3T human functional imaging studies which were unable to distinguish signals from the DG and CA3 hippocampal subfields, did not carry out voxel-wise analyses to test for differences along the long axis of the hippocampus, and left out the amygdala despite its involvement in memory networks.
Young adults completed an object and scene mnemonic discrimination task in a 7-Tesla MRI scanner. Medial temporal lobe (MTL) subregions were manually delineated. Analyses identified regions with a pattern separation-like response of higher activation to lures compared to repeated targets. Such a response is indicative of a region treating a highly similar lure as a novel stimulus.
A voxel-wise analysis showed that across all trials, objects engaged visual ventral areas, perirhinal cortex (BA35+36), and the amygdala relatively more than scene trials. Scenes elicited greater responses in pmERC, subiculum, PHC, and parietal cortex. For the contrast that examined PS-like activity specifically, scene mnemonic discrimination engaged the precuneus, right perirhinal and parahippocampal cortex, and in the hippocampus the posterior DG, CA1, and subiculum subfields. For objects, this was the case for left perirhinal cortex, right anterior CA3 and bilateral amygdala and posterior DG. Analysis of individual trial-type responses showed that CA3 activity could not consistently distinguish between highly similar targets and lures. Consistent with pattern separation, signals in DG and amygdala could make this distinction for objects, while entorhinal cortex did so for objects and scenes. DG activity during mnemonic discrimination was associated with better memory performance, while CA3 and cortical activity were not.
These findings provide further support for a partial distinction between a posterior-medial and anterior-temporal network biased towards scene and object processing, respectively. Regions supporting mnemonic discrimination for scenes were strongly lateralized to the right hemisphere. PS-like responses were largely restricted to the posterior hippocampus. Crucially, several other MTL regions showed responses indicative of pattern separation, more so than in prior 3T studies. The use of 7-Tesla data also made it possible to identify distinct response patterns for DG and CA3 subfields, suggesting that the DG has a greater capacity to resolve feature interference. Importantly, PS-like activation specifically in DG, but not CA3, correlated with better memory performance. These findings provide a more fine-grained map of medial temporal lobe contributions to object and scene memory and highlight the behavioral relevance of dentate gyrus signals for memory fidelity.