Detailed representations of past events rely on the ability to form associations between items and their contextual features (i.e., source memory), as well as the ability to distinctly represent a new event from a similar one stored in memory (i.e., pattern separation). These processes are both known to engage the hippocampus, although whether they share similar mechanisms remains unclear. It is also unknown if, and in which region(s), activity related to these processes overlaps and/or interacts. Here, we used high-resolution fMRI to examine the contributions of hippocampal subfields and neocortical areas to pattern separation and source memory with an experimental paradigm that concurrently tested both. During encoding, male and female human subjects incidentally studied items in one of four quadrants on the screen. During test, they viewed repeated items (targets), similar items (lures), and new items (foils) and were asked to indicate whether each item was old, similar, or new. Following each item judgment, subjects were asked to indicate the quadrant in which the original stimulus was presented. Thus, each lure trial had a lure discrimination component (taxing pattern separation) and a location judgment (source memory). We found two main response profiles: (1) pattern separation-related signals in DG/CA3 and perirhinal cortex and (2) source memory signals in posterior CA1, parahippocampal cortex, and angular gyrus. Whole-brain voxelwise analysis revealed that activity related to lure discrimination and source memory was largely nonoverlapping. These findings suggest that distinct processes underlie the retrieval of pattern separated item representations and recollection of source information.SIGNIFICANCE STATEMENT Recalling past events with detail and accuracy depends on the ability to remember the contextual features of an event (i.e., source memory) as well as the ability to distinguish among similar events in memory (i.e., pattern separation). Previous work has shown that these processes are behaviorally dissociable (e.g., people can have clear memory for context but misidentify people or items). However, both processes engage the hippocampus, and it is unclear whether they rely on shared or distinct neural mechanisms. Here, we used high-resolution fMRI to concurrently assess hippocampal and neocortical activity related to source memory and pattern separation. We found that activity related to these processes was largely nonoverlapping, shedding light on two complementary but distinct mechanisms supporting episodic memory.

The hippocampus plays a critical role in spatial memory. However, the exact neural mechanisms underlying high-fidelity spatial memory representations are unknown. We report findings from presurgical epilepsy patients with bilateral hippocampal depth electrodes performing an object-location memory task that provided a broad range of spatial memory precision. During encoding, patients were shown a series of objects along the circumference of an invisible circle. At test, the same objects were shown at the top of the circle (0°), and patients used a dial to move the object to its location shown during encoding. Angular error between the correct location and the indicated location was recorded as a continuous measure of performance. By registering pre- and postimplantation MRI scans, we were able to localize the electrodes to specific hippocampal subfields. We found a correlation between increased gamma power, thought to reflect local excitatory activity, and the precision of spatial memory retrieval in hippocampal CA1 electrodes. Additionally, we found a similar relationship between gamma power and memory precision in the dorsolateral prefrontal cortex and a directional relationship between activity in this region and in the CA1, suggesting that the dorsolateral prefrontal cortex is involved in postretrieval processing. These results indicate that local processing in hippocampal CA1 and dorsolateral prefrontal cortex supports high-fidelity spatial memory representations.

How do we remember emotional events? While emotion often leads to vivid recollection, the precision of emotional memories can be degraded, especially when discriminating among overlapping experiences in memory (i.e., pattern separation). Communication between the amygdala and the hippocampus has been proposed to support emotional memory, but the exact neural mechanisms remain unclear. Here, we used intracranial recordings in pre-surgical epilepsy patients to show that successful pattern separation of emotional stimuli is associated with theta band (3-7 Hz)-coordinated bidirectional interactions between the amygdala and the hippocampus. In contrast, discrimination errors (i.e., failure to discriminate similar stimuli) were associated with alpha band (7-13 Hz)-coordinated unidirectional influence from the amygdala to the hippocampus. These findings imply that alpha band synchrony may impair discrimination of similar emotional events via the amygdala-hippocampal directional coupling, which suggests a target for treatments of psychiatric conditions such as post-traumatic stress disorder, in which aversive experiences are often overgeneralized.