Electrocorticography reveals the temporal dynamics of posterior parietal cortical activity during recognition memory decisions.

Theories of the neurobiology of episodic memory predominantly focus on the contributions of medial temporal lobe structures, based on extensive lesion, electrophysiological, and imaging evidence. Against this backdrop, functional neuroimaging data have unexpectedly implicated left posterior parietal cortex (PPC) in episodic retrieval, revealing distinct activation patterns in PPC subregions as humans make memory-related decisions. To date, theorizing about the functional contributions of PPC has been hampered by the absence of information about the temporal dynamics of PPC activity as retrieval unfolds. Here, we leveraged electrocorticography to examine the temporal profile of high gamma power (HGP) in dorsal PPC subregions as participants made old/new recognition memory decisions. A double dissociation in memory-related HGP was observed, with activity in left intraparietal sulcus (IPS) and left superior parietal lobule (SPL) differing in time and sign for recognized old items (Hits) and correctly rejected novel items (CRs). Specifically, HGP in left IPS increased for Hits 300-700 ms poststimulus onset, and decayed to baseline ∼200 ms preresponse. By contrast, HGP in left SPL increased for CRs early after stimulus onset (200-300 ms) and late in the memory decision (from 700 ms to response). These memory-related effects were unique to left PPC, as they were not observed in right PPC. Finally, memory-related HGP in left IPS and SPL was sufficiently reliable to enable brain-based decoding of the participant's memory state at the single-trial level, using multivariate pattern classification. Collectively, these data provide insights into left PPC temporal dynamics as humans make recognition memory decisions.

A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals?

The advent of high-resolution magnetic resonance imaging (MRI) has enabled in vivo research in a variety of populations and diseases on the structure and function of hippocampal subfields and subdivisions of the parahippocampal gyrus. Because of the many extant and highly discrepant segmentation protocols, comparing results across studies is difficult. To overcome this barrier, the Hippocampal Subfields Group was formed as an international collaboration with the aim of developing a harmonized protocol for manual segmentation of hippocampal and parahippocampal subregions on high-resolution MRI. In this commentary we discuss the goals for this protocol and the associated key challenges involved in its development. These include differences among existing anatomical reference materials, striking the right balance between reliability of measurements and anatomical validity, and the development of a versatile protocol that can be adopted for the study of populations varying in age and health. The commentary outlines these key challenges, as well as the proposed solution of each, with concrete examples from our working plan. Finally, with two examples, we illustrate how the harmonized protocol, once completed, is expected to impact the field by producing measurements that are quantitatively comparable across labs and by facilitating the synthesis of findings across different studies. © 2016 Wiley Periodicals, Inc.

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.

Where is human V4? Predicting the location of hV4 and VO1 from cortical folding.

A strong relationship between cortical folding and the location of primary sensory areas in the human brain is well established. However, it is unknown if coupling between functional responses and gross anatomy is found at higher stages of sensory processing. We examined the relationship between cortical folding and the location of the retinotopic maps hV4 and VO1, which are intermediate stages in the human ventral visual processing stream. Our data show a consistent arrangement of the eccentricity maps within hV4 and VO1 with respect to anatomy, with the consequence that the hV4/VO1 boundary is found consistently in the posterior transverse collateral sulcus (ptCoS) despite individual variability in map size and cortical folding. Understanding this relationship allowed us to predict the location of visual areas hV4 and VO1 in a separate set of individuals, using only their anatomies, with >85% accuracy. These findings have important implications for understanding the relation between cortical folding and functional maps as well as for defining visual areas from anatomical landmarks alone.

Global similarity and pattern separation in the human medial temporal lobe predict subsequent memory.

Intense debate surrounds the role of medial temporal lobe (MTL) structures in recognition memory. Using high-resolution fMRI and analyses of pattern similarity in humans, we examined the encoding computations subserved by MTL subregions. Specifically, we tested the theory that MTL cortex supports memory by encoding overlapping representations, whereas hippocampus supports memory by encoding pattern-separated representations. Consistent with this view, the relationship between encoding pattern similarity and subsequent memory dissociated MTL cortex and hippocampus: later memory was predicted by greater across-item pattern similarity in perirhinal cortex and in parahippocampal cortex, but greater pattern distinctiveness in hippocampus. Additionally, by comparing neural patterns elicited by individual stimuli regardless of subsequent memory, we found that perirhinal cortex and parahippocampal cortex exhibited differential content sensitivity for multiple stimulus categories, whereas hippocampus failed to demonstrate content sensitivity. These data provide novel evidence that complementary MTL encoding computations subserve declarative memory.

What do differences between multi-voxel and univariate analysis mean? How subject-, voxel-, and trial-level variance impact fMRI analysis.

Multi-voxel pattern analysis (MVPA) has led to major changes in how fMRI data are analyzed and interpreted. Many studies now report both MVPA results and results from standard univariate voxel-wise analysis, often with the goal of drawing different conclusions from each. Because MVPA results can be sensitive to latent multidimensional representations and processes whereas univariate voxel-wise analysis cannot, one conclusion that is often drawn when MVPA and univariate results differ is that the activation patterns underlying MVPA results contain a multidimensional code. In the current study, we conducted simulations to formally test this assumption. Our findings reveal that MVPA tests are sensitive to the magnitude of voxel-level variability in the effect of a condition within subjects, even when the same linear relationship is coded in all voxels. We also find that MVPA is insensitive to subject-level variability in mean activation across an ROI, which is the primary variance component of interest in many standard univariate tests. Together, these results illustrate that differences between MVPA and univariate tests do not afford conclusions about the nature or dimensionality of the neural code. Instead, targeted tests of the informational content and/or dimensionality of activation patterns are critical for drawing strong conclusions about the representational codes that are indicated by significant MVPA results.

Memory monitoring failure in confabulation: evidence from the semantic illusion paradigm.

Several prominent models of confabulation characterize the syndrome as a failure in controlled aspects of memory retrieval, such as pre-retrieval cue specification and post-retrieval monitoring. These models have been generated primarily in the context of studies of autobiographical memory retrieval. Less research has focused on the existence and mechanisms of semantic confabulation. We examined whether confabulation extends to the semantic domain, and if so, whether it could be understood as a monitoring failure. We focus on post-retrieval monitoring by using a verification task that minimizes cue specification demands. We used the semantic illusion paradigm that elicits erroneous endorsement of misleading statements (e.g., "Two animals of each kind were brought onto the Ark by Moses before the great flood") even in controls, despite their knowing the correct answer (e.g., Noah). Monitoring demands were manipulated by varying semantic overlap between target and foils, ranging from high semantic overlap to unrelated. We found that semantic overlap modulated the magnitude of semantic illusion in all groups. Compared to controls, both confabulators and non-confabulators had greater difficulty monitoring semantically related foils; however, elevated endorsement of unrelated foils was unique to confabulators. We interpret our findings in the context of a two-process model of post-retrieval monitoring.

Content Tuning in the Medial Temporal Lobe Cortex: Voxels that Perceive, Retrieve.

How do we recall vivid details from our past based only on sparse cues? Research suggests that the phenomenological reinstatement of past experiences is accompanied by neural reinstatement of the original percept. This process critically depends on the medial temporal lobe (MTL). Within the MTL, perirhinal cortex (PRC) and parahippocampal cortex (PHC) are thought to support encoding and recall of objects and scenes, respectively, with the hippocampus (HC) serving as a content-independent hub. If the fidelity of recall indeed arises from neural reinstatement of perceptual activity, then successful recall should preferentially draw upon those neural populations within content-sensitive MTL cortex that are tuned to the same content during perception. We tested this hypothesis by having eighteen human participants undergo functional MRI (fMRI) while they encoded and recalled objects and scenes paired with words. Critically, recall was cued with the words only. While HC distinguished successful from unsuccessful recall of both objects and scenes, PRC and PHC were preferentially engaged during successful versus unsuccessful object and scene recall, respectively. Importantly, within PRC and PHC, this content-sensitive recall was predicted by content tuning during perception: Across PRC voxels, we observed a positive relationship between object tuning during perception and successful object recall, while across PHC voxels, we observed a positive relationship between scene tuning during perception and successful scene recall. Our results thus highlight content-based roles of MTL cortical regions for episodic memory and reveal a direct mapping between content-specific tuning during perception and successful recall.

Prospective representation of navigational goals in the human hippocampus.

Mental representation of the future is a fundamental component of goal-directed behavior. Computational and animal models highlight prospective spatial coding in the hippocampus, mediated by interactions with the prefrontal cortex, as a putative mechanism for simulating future events. Using whole-brain high-resolution functional magnetic resonance imaging and multi-voxel pattern classification, we tested whether the human hippocampus and interrelated cortical structures support prospective representation of navigational goals. Results demonstrated that hippocampal activity patterns code for future goals to which participants subsequently navigate, as well as for intervening locations along the route, consistent with trajectory-specific simulation. The strength of hippocampal goal representations covaried with goal-related coding in the prefrontal, medial temporal, and medial parietal cortex. Collectively, these data indicate that a hippocampal-cortical network supports prospective simulation of navigational events during goal-directed planning.

Medial temporal lobe contributions to short-term memory for faces.

The role of the medial temporal lobes (MTL) in short-term memory (STM) remains a matter of debate. Whereas imaging studies commonly show hippocampal activation during short-delay memory tasks, evidence from amnesic patients with MTL lesions is mixed. It has been argued that apparent STM impairments in amnesia may reflect long-term memory (LTM) contributions to performance. We challenge this conclusion by demonstrating that MTL amnesic patients show impaired delayed matching-to-sample (DMS) for faces in a task that meets both a traditional delay-based and a recently proposed distractor-based criterion for classification as an STM task. In Experiment 1, we demonstrate that our face DMS task meets the proposed distractor-based criterion for STM classification, in that extensive processing of delay-period distractor stimuli disrupts performance of healthy individuals. In Experiment 2, MTL amnesic patients with lesions extending into anterior subhippocampal cortex, but not patients with lesions limited to the hippocampus, show impaired performance on this task without distraction at delays as short as 8 s, within temporal range of delay-based STM classification, in the context of intact perceptual matching performance. Experiment 3 provides support for the hypothesis that STM for faces relies on configural processing by showing that the extent to which healthy participants' performance is disrupted by interference depends on the configural demands of the distractor task. Together, these findings are consistent with the notion that the amnesic impairment in STM for faces reflects a deficit in configural processing associated with subhippocampal cortices and provide novel evidence that the MTL supports cognition beyond the LTM domain.

Human hippocampal increases in low-frequency power during associative prediction violations.

Environmental cues often trigger memories of past events (associative retrieval), and these memories are a form of prediction about imminent experience. Learning is driven by the detection of prediction violations, when the past and present diverge. Using intracranial electroencephalography (iEEG), we show that associative prediction violations elicit increased low-frequency power (in the slow-theta range) in human hippocampus, that this low-frequency power increase is modulated by whether conditions allow predictions to be generated, that the increase rapidly onsets after the moment of violation, and that changes in low-frequency power are not present in adjacent perirhinal cortex. These data suggest that associative mismatch is computed within hippocampus when cues trigger predictions that are violated by imminent experience.

Intact implicit verbal relational memory in medial temporal lobe amnesia.

To elucidate the role of the hippocampus in unaware relational memory, the present study examined the performance of amnesic patients with medial temporal lobe (MTL) lesions on a cued category-exemplar generation task. In contrast to a prior study in which amnesic patients showed impaired performance (Verfaellie et al., Cognitive, Affective, and Behavioral Neuroscience, 2006, 6, 91-101), the current study employed a task that required active processing of the context word at test. In this version of the task, amnesic patients, like control participants, showed enhanced category exemplar priming when the context word associated with the target at study was reinstated at test. The finding of intact implicit memory for novel associations following hippocampal lesions in a task that requires flexible use of retrieval cues is inconsistent with a relational memory view that suggests that the hippocampus is critical for all forms of relational memory, regardless of awareness. Instead, it suggests that unaware memory for within-domain associations does not require MTL mediation.

Benefits of immediate repetition versus long study presentation on memory in amnesia.

OBJECTIVE: This study aimed to resolve discrepant findings in the literature regarding the effects of massed repetition and a single long study presentation on memory in amnesia. METHOD: Experiment 1 assessed recognition memory in 9 amnesic patients and 18 controls following presentation of a study list that contained items shown for a single short study presentation, a single long study presentation, and three massed repetitions. In Experiment 2, the same encoding conditions were presented in a blocked rather than intermixed format to all participants from Experiment 1. RESULTS: In Experiment 1, control participants showed benefits associated with both types of extended exposure, and massed repetition was more beneficial than long study presentation, F(2, 34) = 14.03, p < .001, partial eta(2) = .45. In contrast, amnesic participants failed to show benefits of either type of extended exposure, F < 1. In Experiment 2, both groups benefited from repetition, but did so in different ways, F(2, 50) = 4.80, p = .012, partial eta(2) = .16. Amnesic patients showed significant and equivalent benefit associated with both types of extended exposure, F(2, 16) = 5.58, p = .015, partial eta(2) = .41, but control participants again benefited more from massed repetition than from long study presentation, F(2, 34) = 23.74, p < .001, partial eta(2) = .58. CONCLUSIONS: The findings suggest that previous inconsistencies in the literature were due to procedural differences across studies. We discuss group differences in terms of the mechanisms by which both forms of extended exposure facilitate performance in each group.