Alison R. Preston

Interplay of Hippocampus and Prefrontal Cortex in Memory

Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation.

High-resolution fmri of content-sensitive subsequent memory responses in human medial temporal lobe

The essential role of the medial temporal lobe (MTL) in long-term memory for individual events is well established, yet important questions remain regarding the mnemonic functions of the component structures that constitute the region. Within the hippocampus, recent functional neuroimaging findings suggest that formation of new memories depends on the dentate gyrus and the CA3 field, whereas the contribution of the subiculum may be limited to retrieval. During encoding, it has been further hypothesized that structures within MTL cortex contribute to encoding in a content-sensitive manner, whereas hippocampal structures may contribute to encoding in a more domain-general manner. In the current experiment, high-resolution fMRI techniques were utilized to assess novelty and subsequent memory effects in MTL subregions for two classes of stimuli—faces and scenes. During scanning, participants performed an incidental encoding (target detection) task with novel and repeated faces and scenes. Subsequent recognition memory was indexed for the novel stimuli encountered during scanning. Analyses revealed voxels sensitive to both novel faces and novel scenes in all MTL regions. However, similar percentages of voxels were sensitive to novel faces and scenes in perirhinal cortex, entorhinal cortex, and a combined region comprising the dentate gyrus, CA2, and CA3, whereas parahippocampal cortex, CA1, and subiculum demonstrated greater sensitivity to novel scene stimuli. Paralleling these findings, subsequent memory effects in perirhinal cortex were observed for both faces and scenes, with the magnitude of encoding activation being related to later memory strength, as indexed by a graded response tracking recognition confidence, whereas subsequent memory effects were scene-selective in parahippocampal cortex. Within the hippocampus, encoding activation in the subiculum correlated with subsequent memory for both stimulus classes, with the magnitude of encoding activation varying in a graded manner with later memory strength. Collectively, these findings suggest a gradient of content sensitivity from posterior (parahippocampal) to anterior (perirhinal) MTL cortex, with MTL cortical regions differentially contributing to successful encoding based on event content. In contrast to recent suggestions, the present data further indicate that the subiculum may contribute to successful encoding irrespective of event content.

Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: Towards a harmonized segmentation protocol

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 T and 7 T. 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.

Comparison of spiral-in/out and spiral-out BOLD fMRI at 1.5 and 3 T

Spiral-in/out functional magnetic resonance imaging (fMRI) methods acquire one image before the echo time (TE) and a second image after TE during each scan. Weighted combination of the two images provides a time series with reduced susceptibility dropout in frontal and medial temporal regions as well as increased signal-to-noise ratio (SNR) in regions of uniform cortex. In this study, task activation with the spiral-in/out method was compared to that with conventional spiral-out acquisitions at two field strengths (1.5 and 3.0 T) using episodic memory encoding, verbal working memory, and affective processing tasks in eight human volunteers. With the conventional spiral-out sequence, greater signal dropout is observed in lateral and medial prefrontal, amygdalar, and medial temporal regions at 3 T relative to 1.5 T, whereas such dropout at 3 T is reduced or mitigated with the spiral-in/out method. Similarly, activation volumes for frontal, amygdalar, and medial temporal regions are reduced for spiral-out acquisitions relative to spiral-in/out, and this difference is more apparent at 3 T than at 1.5 T. In addition, significant regionally specific increases in Z scores are obtained with the spiral-in/out sequence relative to spiral-out acquisitions at both field strengths. It is concluded the spiral-in/out sequence may provide significant advantages over conventional spiral methods, especially at 3 T.

Functional Heterogeneity in Posterior Parietal Cortex Across Attention and Episodic Memory Retrieval

While attention is critical for event memory, debate has arisen regarding the extent to which posterior parietal cortex (PPC) activation during episodic retrieval reflects engagement of PPC-mediated mechanisms of attention. Here, we directly examined the relationship between attention and memory, within and across subjects, using functional magnetic resonance imaging attention-mapping and episodic retrieval paradigms. During retrieval, 4 functionally dissociable PPC regions were identified. Specifically, 2 PPC regions positively tracked retrieval outcomes: lateral intraparietal sulcus (latIPS) indexed graded item memory strength, whereas angular gyrus (AnG) tracked recollection. By contrast, 2 other PPC regions demonstrated nonmonotonic relationships with retrieval: superior parietal lobule (SPL) tracked retrieval reaction time, consistent with a graded engagement of top-down attention, whereas temporoparietal junction displayed a complex pattern of below-baseline retrieval activity, perhaps reflecting disengagement of bottom-up attention. Analyses of retrieval effects in PPC topographic spatial attention maps (IPS0-IPS5; SPL1) revealed that IPS5 and SPL1 exhibited a nonmonotonic relationship with retrieval outcomes resembling that in the SPL region, further suggesting that SPL activation during retrieval reflects top-down attention. While demands on PPC attention mechanisms vary during retrieval attempts, the present functional parcellation of PPC indicates that 2 additional mechanisms (mediated by latIPS and AnG) positively track retrieval outcomes.

The hippocampus and inferential reasoning: building memories to navigate future decisions

A critical aspect of inferential reasoning is the ability to form relationships between items or events that were not experienced together. This review considers different perspectives on the role of the hippocampus in successful inferential reasoning during both memory encoding and retrieval. Intuitively, inference can be thought of as a logical process by which elements of individual existing memories are retrieved and recombined to answer novel questions. Such flexible retrieval is sub-served by the hippocampus and is thought to require specialized hippocampal encoding mechanisms that discretely code events such that event elements are individually accessible from memory. In addition to retrieval-based inference, recent research has also focused on hippocampal processes that support the combination of information acquired across multiple experiences during encoding. This mechanism suggests that by recalling past events during new experiences, connections can be created between newly formed and existing memories. Such hippocampally mediated memory integration would thus underlie the formation of networks of related memories that extend beyond direct experience to anticipate future judgments about the relationships between items and events. We also discuss integrative encoding in the context of emerging evidence linking the hippocampus to the formation of schemas as well as prospective theories of hippocampal function that suggest memories are actively constructed to anticipate future decisions and actions.

Flexible Memories: Differential Roles for Medial Temporal Lobe and Prefrontal Cortex in Cross-Episode Binding

Episodic memory is characterized by rapid formation of new associations that bind information within individual episodes. A powerful aspect of episodic memory is the ability to flexibly apply and recombine information from past experience to guide new behavior. A critical question for memory research is how medial temporal lobe (MTL) and prefrontal cortex (PFC), regions implicated in rapid within-episode binding, further support cross-episode binding in service of mnemonic flexibility. We set to answer this question using an associative inference task in humans that required rapid binding of information across overlapping experiences (AB, BC) to enable successful transfer to novel test probes (AC). Within regions predicting subsequent associative memory for directly learned associations, encoding activation in MTL, including hippocampus and parahippocampal cortex, uniquely predicted success on novel transfer trials both within and across participants, consistent with an integrative encoding mechanism where overlapping experiences are linked into a combined representation during learning. In contrast, during retrieval, PFC activation predicted trial-by-trial transfer success while MTL predicted transfer performance across participants. Moreover, increased MTL-PFC coupling was observed during novel transfer trials compared with retrieval of directly learned associations. These findings suggest that inferential processes support transfer of rapidly acquired experiences to novel events during retrieval where multiple memories are recalled and flexibly recombined in service of successful behavior. Together, these results demonstrate distinct encoding and retrieval mechanisms that support mnemonic flexibility, revealing a unique role for MTL regions in cross-episode binding during encoding and engagement of interactive MTL-PFC processes during flexible transfer at test.

Dissociation between Explicit Memory and Configural Memory in the Human Medial Temporal Lobe

Using functional magnetic resonance imaging, the current study explored the differential mnemonic contributions of the hippocampus and surrounding medial temporal lobe (MTL) cortices to explicit recognition memory and configural learning. Using a task that required processing of repeated and novel visuospatial contexts across multiple trials, we examined MTL activation in relation to 3 forms of learning in a single paradigm: 1) context-independent procedural learning, 2) context-dependent configural learning, and 3) explicit recognition memory. Activations in hippocampus and parahippocampal cortex were associated with explicit memory, differentiating between subsequently remembered and forgotten repeated contexts, but were unrelated to context-dependent configural learning. Activations in regions of perirhinal and entorhinal cortex were associated with configural learning of repeated contexts independent from explicit memory for those contexts. Procedural learning was unrelated to activation in any MTL region. The time course of activation across learning further differed in MTL subregions with MTL cortex demonstrating repetition-related decreases and hippocampus repetition-related increases. These repetition effects were differentially sensitive to recognition with only activation in hippocampus and parahippocampal cortex tracking recognized items. These imaging findings converge with studies of amnesia and indicate dissociable roles for hippocampus in learning that supports explicit recognition and for anterior MTL cortex in configural learning.

Awareness in classical differential eyeblink conditioning in young and aging humans

The role of awareness and its impact on learning the conditioned eyeblink response was investigated in both trace and delay discrimination eyeblink conditioning in young and aging participants, in 4 paradigms: delay 750, delay 1,250, trace 500, and trace 1,000. Participants concurrently watched a silent movie about which they were questioned afterward. Acquisition in both the trace and delay discrimination task was correlated with awareness of conditioning stimulus contingencies, regardless of age. Age-dependent deficits were observed in trace discrimination but not in delay discrimination, with more severe deficits appearing at the longer trace interval. The percentage of aware participants was also found to be greater in the young population than in the aging population. These results indicate that awareness or knowledge of stimulus contingencies may be an important contributor to successful acquisition in higher order discrimination tasks.

Learning-related representational changes reveal dissociable integration and separation signatures in the hippocampus and prefrontal cortex

The episodic memory system enables accurate retrieval while maintaining flexibility by representing both specific episodes and generalizations across events. Although theories suggest that the hippocampus (HPC) is dedicated to represent specific episodes while the medial prefrontal cortex (MPFC) generalizes, other accounts posit that HPC can also integrate related memories. Here we use high-resolution functional magnetic resonance imaging in humans to examine how representations of memory elements change to either differentiate or generalize across related events. We show that while posterior HPC and anterior MPFC maintain distinct memories for individual events, anterior HPC and posterior MPFC integrate across memories. Integration is particularly likely for established memories versus those encoded simultaneously, highlighting the greater impact of prior knowledge on new encoding. We also show dissociable coding signatures in ventrolateral PFC, a region previously implicated in interference resolution. These data highlight how memory elements are represented to simultaneously promote generalization across memories and protect from interference.