OBJECTIVE An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1–3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol. METHOD MRI scans of a single healthy adult human subject were acquired both at 3 Tesla and 7 Tesla. Representatives from 21 research groups applied their respective manual segmentation protocols to the MRI modalities of their choice. The resulting set of 21 segmentations was analyzed in a common anatomical space to quantify similarity and identify areas of agreement. RESULTS The differences between the 21 protocols include the region within which segmentation is performed, the set of anatomical labels used, and the extents of specific anatomical labels. The greatest overall disagreement among the protocols is at the CA1/subiculum boundary, and disagreement across all structures is greatest in the anterior portion of the hippocampal formation relative to the body and tail. CONCLUSIONS The combined examination of the 21 protocols in the same dataset suggests possible strategies towards developing a harmonized subfield segmentation protocol and facilitates comparison between published studies.

Summary Structured knowledge is thought to form, in part, through the extraction and representation of regularities across overlapping experiences. However, little is known about how consolidation processes may transform novel episodic memories to reflect such regularities. In a multi-day fMRI study, participants encoded trial-unique associations that shared features with other trials. Multi-variate pattern analyses were used to measure neural similarity across overlapping and non-overlapping memories during immediate and one-week retrieval of these associations. We found that neural patterns in the hippocampus and medial prefrontal cortex represented the featural overlap across memories, but only after a week. Furthermore, after a week, the strength of a memory's unique episodic reinstatement during retrieval was inversely related to its representation of overlap, suggesting a trade-off between the integration of related memories and recovery of episodic details. These findings suggest that consolidation-related changes in neural representations support the gradual organization of discrete episodes into structured knowledge.

Reward motivation has been demonstrated to enhance declarative memory by facilitating systems-level consolidation. Although highreward information is often intermixed with lower reward information during an experience, memory for high value information is prioritized. How is this selectivity achieved? One possibility is that postencoding consolidation processes bias memory strengthening to those representations associated with higher reward. To test this hypothesis, we investigated the influence of differential reward motivation on the selectivity of postencoding markers of systems-level memory consolidation. Human participants encoded intermixed, trial-unique memoranda that were associated with either high or low-value during fMRI acquisition. Encoding was interleaved with periods of rest, allowing us to investigate experience-dependent changes in connectivity as they related to later memory. Behaviorally, we found that reward motivation enhanced 24 h associative memory. Analysis of patterns of postencoding connectivity showed that, even though learning trials were intermixed, there was significantly greater connectivity with regions of high-level, category-selective visual cortex associated with high-reward trials. Specifically, increased connectivity of category-selective visual cortex with both the VTA and the anterior hippocampus predicted associative memory for high-but not low-reward memories. Critically, these results were independent of encoding-related connectivity and univariate activity measures. Thus, these findings support a model by which the selective stabilization of memories for salient events is supported by postencoding interactions with sensory cortex associated with reward.

It is well established that the hippocampus and perirhinal cortex (PrC) encode associative and item representations, respectively. However, less is known about how item and associative memories are consolidated. We used high-resolution fMRI in humans to measure how functional connectivity between these distinct medial temporal lobe regions with the ventral tegmental area (VTA) after a paired associate encoding task is related to both immediate and 24 h item and associative memory performance. We found that the strength of post-encoding functional connectivity between the VTA and CA1 selectively correlated with long-term associative memory, despite subjects actively engaging in an unrelated task during this period. Conversely, VTA-PrC functional connectivity during the same period correlated with long-term item memory. Critically, connectivity between VTA and these MTL regions were only related to memory tested at a 24 h delay, implicating midbrain connectivity in the consolidation of distinct forms of memory.

Determining how the hippocampus supports the unique demands of memory encoding and retrieval is fundamental for understanding the biological basis of episodic memory. One possibility proposed by theoretical models is that the distinct computational demands of encoding and retrieval are accommodated by shifts in the functional interaction between the hippocampal CA1 subregion and its input structures. However, empirical tests of this hypothesis are lacking. To test this in humans, we used high-resolution fMRI to measure functional connectivity between hippocampal area CA1 and regions of the medial temporal lobe and midbrain during extended blocks of associative encoding and retrieval tasks. We found evidence for a double dissociation between the pathways supporting successful encoding and retrieval. Specifically, during the associative encoding task, but not the retrieval task, functional connectivity only between area CA1 and the ventral tegmental area predicted associative long-term memory. In contrast, connectivity between area CA1 and DG/CA3 was greater, on average, during the retrieval task compared with the encoding task, and, importantly, the strength of this connectivity significantly correlated with retrieval success. Together, these findings serve as an important first step toward understanding how the demands of fundamental memory processes may be met by changes in the relative strength of connectivity within hippocampal pathways.Key words: CA1; CA3; functional connectivity; high-resolution fMRI; hippocampus; VTA IntroductionIn everyday experience, memory encoding and retrieval appear seamlessly intertwined; encoding provides material that will later be retrieved, whereas retrieval supplies context to facilitate meaningful encoding. However, the neural mechanisms thought to underlie these processes have been hypothesized to place opposing demands on the episodic memory system (Marr, 1971;O'Reilly and McClelland, 1994). Specifically, the rapid formation of memory traces representing single episodes requires high levels of synaptic plasticity that, during retrieval, could lead to the overwriting of stored memories. Conversely, successful associative retrieval requires that cues reactivate related memory traces and thus benefits from a low threshold for memory reinstatement, but reinstating related memories at the time of encoding could lead to proactive interference (O'Reilly and McClelland, 1994).Although it is generally agreed that the hippocampus is critical for both encoding and retrieval (Scoville and Milner, 1957;Eichenbaum et al., 2007; Squire et al., 2007), it remains unknown how the hippocampus supports the complex demands of both processes. However, the unique pattern of afferent projections converging on area CA1, the major hippocampal output subregion, may provide an answer. On the one hand, inputs to CA1 might differentially support long-term memory encoding. Specifically, both late-phase long-term potentiation (LTP) at CA1 synapses and long-term memory formation have been demonstrated to be...