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Quantitative analyses were performed on computer tomography (CT) scans from 7 patients with Korsakoff's syndrome, 7 age-matched alcoholic subjects, and 7 age-matched healthy control subjects. CT values were used to estimate tissue density and fluid volume in specified brain areas. Tissue density was assessed by averaging CT values in small (5 x 5 mm) areas sampled bilaterally in 6 specified areas--thalamus, head of the caudate nucleus, putamen, anterior white matter, posterior white matter, and centrum semiovale. We assessed fluid volume using a semiautomated computer algorithm that estimated the proportion of fluid in 7 brain regions--total ventricular space, third ventricle, interventricular region, frontal sulci, peri-Sylvian region, medial cerebellum, and vertex. For the patients with Korsakoff's syndrome, we also assessed the correlation between CT measures and performance on 6 cognitive and 12 memory tests. Compared with alcoholic subjects and healthy control subjects, patients with Korsakoff's syndrome had lower CT density values bilaterally in the region of the thalamus and had greater estimated fluid bilaterally in the region of the third ventricle. Alcoholic and healthy control subjects did not differ on these measures. Significant cortical atrophy in frontal sulcal and peri-Sylvian areas was detected both in patients with Korsakoff's syndrome and in alcoholic subjects. For patients with Korsakoff's syndrome, impairment on behavioral tests, and on memory tests in particular, was correlated with low-density values in the thalamus and with high fluid values in the region of the frontal sulci. Damage to diencephalic and frontal areas may especially contribute to the memory and cognitive impairment exhibited by patients with Korsakoff's syndrome.

An important question about the organization of memory is whether information available in non-declarative memory can contribute to performance on tasks of declarative memory. Dorfman, Kihlstrom, Cork, and Misiaszek (1995) described a circumstance in which the phenomenon of priming might benefit recognition memory performance. They reported that patients receiving electroconvulsive therapy improved their recognition performance when they were encouraged to relax their criteria for endorsing test items as familiar. It was suggested that priming improved recognition by making information available about the familiarity of test items. In three experiments, we sought unsuccessfully to reproduce this phenomenon in amnesic patients. In Experiment 3, we reproduced the methods and procedure used by Dorfman et al. but still found no evidence for improved recognition memory following the manipulation of decision criteria. Although negative findings have their own limitations, our findings suggest that the phenomenon reported by Dorfman et al. does not generalize well. Our results agree with several recent findings that suggest that priming is independent of recognition memory and does not contribute to recognition memory scores. [ABSTRACT FROM AUTHOR]

Prior studies of the neural representation of episodic memory in the human hippocampus have identified generic memory signals representing the categorical status of test items (novel vs. repeated), whereas other studies have identified item specific memory signals representing individual test items. Here, we report that both kinds of memory signals can be detected in hippocampal neurons in the same experiment. We recorded single-unit activity from four brain regions (hippocampus, amygdala, anterior cingulate, and prefrontal cortex) of epilepsy patients as they completed a continuous recognition task. The generic signal was found in all four brain regions, whereas the item-specific memory signal was detected only in the hippocampus and reflected sparse coding. That is, for the item-specific signal, each hippocampal neuron responded strongly to a small fraction of repeated words, and each repeated word elicited strong responding in a small fraction of neurons. The neural code was sparse, pattern-separated, and limited to the hippocampus, consistent with longstanding computational models. We suggest that the item-specific episodic memory signal in the hippocampus is fundamental, whereas the more widespread generic memory signal is derivative and is likely used by different areas of the brain to perform memory-related functions that do not require item-specific information.

A degraded, black-and-white image of an object, which appears meaningless on first presentation, is easily identified after a single exposure to the original, intact image. This striking example of perceptual learning reflects a rapid (one-trial) change in performance, but the kind of learning that is involved is not known. We asked whether this learning depends on conscious (hippocampus-dependent) memory for the images that have been presented or on an unconscious (hippocampus-independent) change in the perception of images, independently of the ability to remember them. We tested five memory-impaired patients with hippocampal lesions or larger medial temporal lobe (MTL) lesions. In comparison to volunteers, the patients were fully intact at perceptual learning, and their improvement persisted without decrement from 1 d to more than 5 mo. Yet, the patients were impaired at remembering the test format and, even after 1 d, were impaired at remembering the images themselves. To compare perceptual learning and remembering directly, at 7 d after seeing degraded images and their solutions, patients and volunteers took either a naming test or a recognition memory test with these images. The patients improved as much as the volunteers at identifying the degraded images but were severely impaired at remembering them. Notably, the patient with the most severe memory impairment and the largest MTL lesions performed worse than the other patients on the memory tests but was the best at perceptual learning. The findings show that one-trial, long-lasting perceptual learning relies on hippocampus-independent (nondeclarative) memory, independent of any requirement to consciously remember., Competing Interests: The authors declare no competing interest.

We report neuropsychological and neuropathological findings for a patient (A.B.), who developed memory impairment after a cardiac arrest at age 39. A.B. was a clinical psychologist who, although unable to return to work, was an active participant in our neuropsychological studies for 24 y. He exhibited a moderately severe and circumscribed impairment in the formation of long-term, declarative memory (anterograde amnesia), together with temporally graded retrograde amnesia covering ∼5 y prior to the cardiac arrest. More remote memory for both facts and autobiographical events was intact. His neuropathology was extensive and involved the medial temporal lobe, the diencephalon, cerebral cortex, basal ganglia, and cerebellum. In the hippocampal formation, there was substantial cell loss in the CA1 and CA3 fields, the hilus of the dentate gyrus (with sparing of granule cells), and the entorhinal cortex. There was also cell loss in the CA2 field, but some remnants remained. The amygdala demonstrated substantial neuronal loss, particularly in its deep nuclei. In the thalamus, there was damage and atrophy of the anterior nuclear complex, the mediodorsal nucleus, and the pulvinar. There was also loss of cells in the medial and lateral mammillary nuclei in the hypothalamus. We suggest that the neuropathology resulted from two separate factors: the initial cardiac arrest (and respiratory distress) and the recurrent seizures that followed, which led to additional damage characteristic of temporal lobe epilepsy., Competing Interests: The authors declare no competing interest.

Encoding activity in the medial temporal lobe, presumably evoked by the presentation of stimuli (postonset activity), is known to predict subsequent memory. However, several independent lines of research suggest that preonset activity also affects subsequent memory. We investigated the role of preonset and postonset single-unit and multiunit activity recorded from epilepsy patients as they completed a continuous recognition task. In this task, words were presented in a continuous series and eventually began to repeat. For each word, the patient's task was to decide whether it was novel or repeated. We found that preonset spiking activity in the hippocampus (when the word was novel) predicted subsequent memory (when the word was later repeated). Postonset activity during encoding also predicted subsequent memory, but was simply a continuation of preonset activity. The predictive effect of preonset spiking activity was much stronger in the hippocampus than in three other brain regions (amygdala, anterior cingulate, and prefrontal cortex). In addition, preonset and postonset activity around the encoding of novel words did not predict memory performance for novel words (i.e., correctly classifying the word as novel), and preonset and postonset activity around the time of retrieval did not predict memory performance for repeated words (i.e., correctly classifying the word as repeated). Thus, the only predictive effect was between preonset activity (along with its postonset continuation) at the time of encoding and subsequent memory. Taken together, these findings indicate that preonset hippocampal activity does not reflect general arousal/attention but instead reflects what we term "attention to encoding.", Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Prior knowledge about the probabilistic structure of visual environments is necessary to resolve ambiguous information about objects in the world. Expectations based on stimulus regularities exert a powerful influence on human perception and decision making by improving the efficiency of information processing. Another type of prior knowledge, termed top-down attention, can also improve perceptual performance by facilitating the selective processing of relevant over irrelevant information. While much is known about attention, the mechanisms that support expectations about statistical regularities are not well-understood. The hippocampus has been implicated as a key structure involved in or perhaps necessary for the learning of statistical regularities, consistent with its role in various kinds of learning and memory. Here, we tested this hypothesis using a motion discrimination task in which we manipulated the most likely direction of motion, the degree of attention afforded to the relevant stimulus, and the amount of available sensory evidence. We tested memory-impaired patients with bilateral damage to the hippocampus and compared their performance with controls. Despite a modest slowing in response initiation across all task conditions, patients performed similar to controls. Like controls, patients exhibited a tendency to respond faster and more accurately when the motion direction was more probable, the stimulus was better attended, and more sensory evidence was available. Together, these findings demonstrate a robust, hippocampus-independent capacity for learning statistical regularities in the sensory environment in order to improve information processing., Competing Interests: The authors declare no conflict of interest.

To explore whether the hippocampus might be important for certain spatial operations in addition to its well-known role in memory, we administered two tasks in which participants judged whether objects embedded in scenes or whether scenes themselves could exist in 3-D space. Patients with damage limited to the hippocampus performed as well as controls in both tasks. A patient with large medial-temporal lobe lesions had a bias to judge objects in scenes and scenes themselves as possible, performing well with possible stimuli but poorly with impossible stimuli in both tasks. All patients were markedly impaired at remembering the tasks. The hippocampus appears not to be essential for judging the structural coherence of objects in scenes or the coherence of scenes. The findings conform to what is now a sizeable literature emphasizing the importance of the hippocampus for memory. We discuss our results in light of findings that other patients have sometimes been reported to be disadvantaged by spatial tasks like the ones studied here, despite less hippocampal damage and milder memory impairment.

We studied the narrative recollections of memory-impaired patients with medial temporal lobe (MTL) damage who took a 25-min guided walk during which 11 planned events occurred. The recollections of the patients, recorded directly after the walk, were compared with the recollections of controls tested directly after the walk (C1), after one month (C2), or after 2.6 years (C3). With respect to memory for the walk, the narrative recollections of the patients were impoverished compared with C1 but resembled the recollections of volunteers tested after long delays (C2 and C3). In addition, how language was used by the patients in their recollections resembled how language was used by groups C2 and C3 (higher-frequency words, less concrete words, fewer nouns, more adverbs, more pronouns, and more indefinite articles). These findings appear to reflect how individuals, either memory-impaired patients or controls, typically speak about the past when memory is weak and lacks detail and need not have special implications about language use and MTL function beyond the domain of memory. A notable exception to the similarity between patient narratives and the narratives of C2 and C3 was that the control groups reported the events of the walk in correct chronological order, whereas the order in which patients reported events bore no relationship to the order in which events occurred. We suggest that the MTL is especially important for accessing global information about events and the relationships among their elements., Competing Interests: The authors declare no conflict of interest.

We explored the relationship between memory performance and conscious knowledge (or awareness) of what has been learned in memory-impaired patients with hippocampal lesions or larger medial temporal lesions. Participants viewed familiar scenes or familiar scenes where a change had been introduced. Patients identified many fewer of the changes than controls. Across all of the scenes, controls preferentially directed their gaze toward the regions that had been changed whenever they had what we term robust knowledge about the change: They could identify that a change occurred, report what had changed, and indicate where the change occurred. Preferential looking did not occur when they were unaware of the change or had only partial knowledge about it. The patients, overall, did not direct their gaze toward the regions that had been changed, but on the few occasions when they had robust knowledge about the change they (like controls) did exhibit this effect. Patients did not exhibit this effect when they were unaware of the change or had partial knowledge. The findings support the idea that awareness of what has been learned is a key feature of hippocampus-dependent memory., Competing Interests: The authors declare no conflict of interest.

When individuals select the recently studied (and familiar) item in a multiple-choice memory test, they direct a greater proportion of viewing time toward the to-be-selected item when their choice is correct than when their choice is incorrect. Thus, for both correct and incorrect choices, individuals indicate that the chosen item is old, but viewing time nevertheless distinguishes between old and new items. What kind of memory supports this preferential viewing effect? We recorded eye movements while participants made three-alternative, forced-choice recognition memory judgments for scenes. In experiment 1 ( n = 30), the magnitude of the preferential viewing effect was strongly correlated with measures of conscious, declarative memory: recognition accuracy as well as the difference in confidence ratings and in response times for correct and incorrect choices. In four analyses that minimized the contribution of declarative memory in order to detect a possible contribution from other processes, the preferential viewing effect was absent. In experiment 2, five memory-impaired patients with medial temporal lobe lesions exhibited a diminished preferential viewing effect. These patients also exhibited poor recognition accuracy and reduced differences in confidence ratings and response times for correct and incorrect choices. We propose that the preferential viewing effect is a phenomenon of conscious, declarative memory and is dependent on the medial temporal lobe. The findings support the link between medial temporal lobe function and declarative memory. When the effects of experience depend on the medial temporal lobe, the effects reflect conscious memory., Competing Interests: The authors declare no conflict of interest.

The hippocampus has long been recognized as important for the formation of long-term memory. Recent work has suggested that the hippocampus might also be important for certain kinds of spatial operations, as in constructing scenes, shifting perspective, or perceiving the geometry of scenes and their boundaries. We explored this proposal using a task similar to one used previously that related hippocampal activity to scenes and their boundaries. In our study, participants viewed scenes from above that displayed walls and towers. After viewing each scene, participants saw a scene from ground level and judged whether it was the same as or different from the scene just presented. The number of towers and walls in each scene was manipulated so that it was possible to assess how the structure of the scene affected performance. Patients with hippocampal lesions performed similarly to controls in all task conditions and had no special difficulty as a function of the layout of a scene and its boundaries. In contrast, a patient with large medial temporal lobe (MTL) lesions was impaired. Taken together, our findings suggest that the hippocampus is not needed for scene construction, shifts in perspective, or perceiving the geometry of scenes. The impairment associated with large MTL lesions may result from damage in or near parahippocampal cortex., (© 2018 Rungratsameetaweemana and Squire; Published by Cold Spring Harbor Laboratory Press.)

We tested the proposal that medial temporal lobe (MTL) structures support not just memory but also high-level object perception. In one task, participants decided whether a line drawing could represent an object in three-dimensional space and, in another task, they saw the components of an object and decided what object could be formed if the components were assembled. Patients with hippocampal lesions were intact, indicating that the hippocampus is not needed for perceiving the structural coherence of objects or appreciating the relations among object parts. Patients with large MTL lesions were moderately impaired, likely due to damage outside the MTL., (© 2018 Urgolites et al.; Published by Cold Spring Harbor Laboratory Press.)

Prior experience has been shown to improve learning in both humans and animals, but it is unclear what aspects of recent experience are necessary to produce beneficial effects. Here, we examined the capacity of rats with complete hippocampal lesions, restricted CA1 lesions, or sham surgeries to benefit from prior experience. Animals were tested in two different spatial tasks in the watermaze, the conventional watermaze task and delayed match-to-position. The two lesions impaired performance in both tasks when rats had no prior experience. However, when given prior training with one task, CA1 lesions had no effect on performance in the other task. In contrast, rats with hippocampal lesions did not benefit from prior training. The findings show that prior experience can benefit learning even when the previously learned task and a new task are quite different. The concept of schema may be useful for understanding the benefits of prior experience., (© 2018 Ocampo et al.; Published by Cold Spring Harbor Laboratory Press.)

Neurocomputational models have long posited that episodic memories in the human hippocampus are represented by sparse, stimulus-specific neural codes. A concomitant proposal is that when sparse-distributed neural assemblies become active, they suppress the activity of competing neurons (neural sharpening). We investigated episodic memory coding in the hippocampus and amygdala by measuring single-neuron responses from 20 epilepsy patients (12 female) undergoing intracranial monitoring while they completed a continuous recognition memory task. In the left hippocampus, the distribution of single-neuron activity indicated that only a small fraction of neurons exhibited strong responding to a given repeated word and that each repeated word elicited strong responding in a different small fraction of neurons. This finding reflects sparse distributed coding. The remaining large fraction of neurons exhibited a concurrent reduction in firing rates relative to novel words. The observed pattern accords with longstanding predictions that have previously received scant support from single-cell recordings from human hippocampus., Competing Interests: The authors declare no conflict of interest.

Hippocampal lesions often produce temporally graded retrograde amnesia (TGRA), whereby recent memory is impaired more than remote memory. This finding has provided support for the process of systems consolidation. However, temporally graded memory impairment has not been observed with the watermaze task, and the findings have been inconsistent with context fear conditioning. One possibility is that large hippocampal lesions indirectly disrupt (by retrograde degeneration) the function of areas that project to the hippocampus that are important for task performance or thought to be important for storing consolidated memories. We developed a discrete lesion targeting area CA1, the sole output of the hippocampus to neocortex, and tested the effects of this lesion on recent and remote memory in the watermaze task, in context fear conditioning, and in trace fear conditioning. In all three tasks, recent and remote memory were similarly impaired after CA1 lesions. We discuss factors that help to illuminate these findings and consider their relevance to systems consolidation., (© 2017 Ocampo et al.; Published by Cold Spring Harbor Laboratory Press.)

There has been interest in the idea that medial temporal lobe (MTL) structures might be especially important for spatial processing and spatial memory. We tested the proposal that the MTL has a specific role in topographical memory as assessed in tasks of scene memory where the viewpoint shifts from study to test. Building on materials used previously for such studies, we administered three different tasks in a total of nine conditions. Participants studied a scene depicting four hills of different shapes and sizes and made a choice among four test images. In the Rotation task, the correct choice depicted the study scene from a shifted perspective. MTL patients succeeded when the study and test images were presented together but failed the moment the study scene was removed (even at a 0-s delay). In the No-Rotation task, the correct choice was a duplicate of the study scene. Patients were impaired to the same extent in the No-Rotation and Rotation tasks after matching for difficulty. Thus, an inability to accommodate changes in viewpoint does not account for patient impairment. In the Nonspatial-Perceptual task, the correct choice depicted the same overall coloring as the study scene. Patients were intact at a 2-s delay but failed at longer, distraction-filled delays. The different results for the spatial and nonspatial tasks are discussed in terms of differences in demand on working memory. We suggest that the difficulty of the spatial tasks rests on the neocortex and on the limitations of working memory, not on the MTL., Competing Interests: The authors declare no conflict of interest.

A central idea about the organization of declarative memory and the function of the hippocampus is that the hippocampus provides for the coding of relationships between items. A question arises whether this idea refers to the process of forming long-term memory or whether, as some studies have suggested, memory for relations might depend on the hippocampus even at short retention intervals and even when the task falls within the province of short-term (working) memory. The latter formulation appears to place the operation of relational memory into conflict with the idea that working memory is independent of medial temporal lobe (MTL) structures. In this report, the concepts of relational memory and working memory are discussed in the light of a simple demonstration experiment. Patients with MTL lesions successfully learned and recalled two word pairs when tested directly after learning but failed altogether when tested after a delay. The results do not contradict the idea that the hippocampus has a fundamental role in relational memory. However, there is a need for further elaboration and specification of the idea in order to explain why patients with MTL lesions can establish relational memory in the short term but not in long-term memory. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Eye movements can reflect memory. For example, participants make fewer fixations and sample fewer regions when viewing old versus new scenes (the repetition effect). It is unclear whether the repetition effect requires that participants have knowledge (awareness) of the old-new status of the scenes or if it can occur independent of knowledge about old-new status. It is also unclear whether the repetition effect is hippocampus-dependent or hippocampus-independent. A complication is that testing conscious memory for the scenes might interfere with the expression of unconscious (unaware), experience-dependent eye movements. In experiment 1, 75 volunteers freely viewed old and new scenes without knowledge that memory for the scenes would later be tested. Participants then made memory judgments and confidence judgments for each scene during a surprise recognition memory test. Participants exhibited the repetition effect regardless of the accuracy or confidence associated with their memory judgments (i.e., the repetition effect was independent of their awareness of the old-new status of each scene). In experiment 2, five memory-impaired patients with medial temporal lobe damage and six controls also viewed old and new scenes without expectation of memory testing. Both groups exhibited the repetition effect, even though the patients were impaired at recognizing which scenes were old and which were new. Thus, when participants viewed scenes without expectation of memory testing, eye movements associated with old and new scenes reflected unconscious, hippocampus-independent memory. These findings are consistent with the formulation that, when memory is expressed independent of awareness, memory is hippocampus-independent., (Published by Cold Spring Harbor Laboratory Press.)

We administered map-reading tasks in which participants navigated an array of marks on the floor by following paths on hand-held maps that made up to nine turns. The burden on memory was minimal because the map was always available. Nevertheless, because the map was held in a fixed position in relation to the body, spatial computations were continually needed to transform map coordinates into geographical coordinates as participants followed the maps. Patients with lesions limited to the hippocampus (n = 5) performed similar to controls at all path lengths (experiment 1). They were also intact at executing single moves to an adjacent location, even when trials began by facing in a direction that put the map coordinates and geographical coordinates into conflict (experiment 2). By contrast, one patient with large medial temporal lobe (MTL) lesions performed poorly overall in experiment 1 and poorly in experiment 2 when trials began by facing in the direction that placed the map coordinates and geographical coordinates in maximal conflict. Directly after testing, all patients were impaired at remembering factual details about the task. The findings suggest that the hippocampus is not needed to carry out the spatial computations needed for map reading and navigating from maps. The impairment in map reading associated with large MTL lesions may depend on damage in or near the parahippocampal cortex., Competing Interests: The authors declare no conflict of interest.

In earlier work, patients with hippocampal damage successfully path integrated, apparently by maintaining spatial information in working memory. In contrast, rats with hippocampal damage were unable to path integrate, even when the paths were simple and working memory might have been expected to support performance. We considered possible ways to understand these findings. We tested rats with either hippocampal lesions or lesions of medial prefrontal cortex (mPFC) on three tasks of spatial or nonspatial memory: path integration, spatial alternation, and a nonspatial alternation task. Rats with mPFC lesions were impaired on both spatial and nonspatial alternation but performed normally on path integration. By contrast, rats with hippocampal lesions were impaired on path integration and spatial alternation but performed normally on nonspatial alternation. We propose that rodent neocortex is limited in its ability to construct a coherent spatial working memory of complex environments. Accordingly, in tasks such as path integration and spatial alternation, working memory cannot depend on neocortex alone. Rats may accomplish many spatial memory tasks by relying on long-term memory. Alternatively, they may accomplish these tasks within working memory through sustained coordination between hippocampus and other cortical brain regions such as mPFC, in the case of spatial alternation, or parietal cortex in the case of path integration. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

The hippocampus is important for autobiographical memory, but its role is unclear. In the study, patients with hippocampal damage and controls were taken on a 25-min walk on the University of California, San Diego, campus during which 11 planned events occurred. Memory was tested directly after the walk. In addition, a second group of controls took the same walk and were tested after 1 mo. Patients with hippocampal damage remembered fewer details than controls tested directly after the walk but remembered a similar number of details as controls tested after 1 mo. Notably, the details that were reported by patients had the characteristics of episodic recollection and included references to particular places and events. Patients exhibited no special difficulty remembering spatial details in comparison with nonspatial details. Last, whereas both control groups tended to recall the events of the walk in chronological order, the order in which patients recalled the events was unrelated to the order in which they occurred. The findings illuminate the role of the hippocampus in autobiographical memory and in the spatial and nonspatial aspects of episodic recollection., Competing Interests: The authors declare no conflict of interest.

In two experiments, patients with damage to the medial temporal lobe (MTL) and healthy controls produced detailed autobiographical narratives as they remembered past events (recent and remote) and imagined future events (near and distant). All recent events occurred after the onset of memory impairment. The first experiment aimed to replicate the methods of Race et al. [Race E, Keane MM, Verfaellie M (2011) J Neurosci 31(28):10262-10269]. Transcripts from that study were kindly made available for independent analysis, which largely reproduced the findings from that study. Our patients produced marginally fewer episodic details than controls. Patients from the earlier study were more impaired than our patients. Patients in both groups had difficulty in returning to their narratives after going on tangents, suggesting that anterograde memory impairment may have interfered with narrative construction. In experiment 2, the experimenter used supportive questioning to help keep participants on task and reduce the burden on anterograde memory. This procedure increased the number of details produced by all participants and rescued the performance of our patients for the distant past. Neither of the two patient groups had any special difficulty in producing spatial details. The findings suggest that constructing narratives about the remote past and the future does not depend on MTL structures, except to the extent that anterograde amnesia affects performance. The results further suggest that different findings about the status of autobiographical memory likely depend on differences in the location and extent of brain damage in different patient groups., Competing Interests: In 2013, Dr. Kirwan kindly administered some tests to two patients he had access to. Subsequently, he was a middle author on the resulting PNAS paper [Smith CN, et al. (2014) When recognition memory is independent of hippocampal function. Proc Natl Acad Sci 111(27):9935–9940]. The authors do not regard this as a conflict of interest, as Dr. Kirwan had no part in the planning, interpretation, or writing, and did not participate in any discussions about the project.

Recent studies have asked whether activity in the medial temporal lobe (MTL) and the neocortex can distinguish true memory from false memory. A frequent complication has been that the confidence associated with correct memory judgments (true memory) is typically higher than the confidence associated with incorrect memory judgments (false memory). Accordingly, it has often been difficult to know whether a finding is related to memory confidence or memory accuracy. In the current study, participants made recognition memory judgments with confidence ratings in response to previously studied scenes and novel scenes. The left hippocampus and 16 other brain regions distinguished true and false memories when confidence ratings were different for the two conditions. Only three regions (all in the parietal cortex) distinguished true and false memories when confidence ratings were equated. These findings illustrate the utility of taking confidence ratings into account when identifying brain regions associated with true and false memories. Neural correlates of true and false memories are most easily interpreted when confidence ratings are similar for the two kinds of memories., (Published by Cold Spring Harbor Laboratory Press.)

Conscious memory for a new experience is initially dependent on information stored in both the hippocampus and neocortex. Systems consolidation is the process by which the hippocampus guides the reorganization of the information stored in the neocortex such that it eventually becomes independent of the hippocampus. Early evidence for systems consolidation was provided by studies of retrograde amnesia, which found that damage to the hippocampus-impaired memories formed in the recent past, but typically spared memories formed in the more remote past. Systems consolidation has been found to occur for both episodic and semantic memories and for both spatial and nonspatial memories, although empirical inconsistencies and theoretical disagreements remain about these issues. Recent work has begun to characterize the neural mechanisms that underlie the dialogue between the hippocampus and neocortex (e.g., "neural replay," which occurs during sharp wave ripple activity). New work has also identified variables, such as the amount of preexisting knowledge, that affect the rate of consolidation. The increasing use of molecular genetic tools (e.g., optogenetics) can be expected to further improve understanding of the neural mechanisms underlying consolidation., (Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.)

We evaluated two different perspectives about the function of the human hippocampus--one that emphasizes the importance of memory and another that emphasizes the importance of spatial processing and scene construction. We gave tests of boundary extension, scene construction, and memory to patients with lesions limited to the hippocampus or large lesions of the medial temporal lobe. The patients were intact on all of the spatial tasks and impaired on all of the memory tasks. We discuss earlier studies that associated performance on these spatial tasks to hippocampal function. Our results demonstrate the importance of medial temporal lobe structures for memory and raise doubts about the idea that these structures have a prominent role in spatial cognition.

The idea that memory is not a single mental faculty has a long and interesting history but became a topic of experimental and biologic inquiry only in the mid-20th century. It is now clear that there are different kinds of memory, which are supported by different brain systems. One major distinction can be drawn between working memory and long-term memory. Long-term memory can be separated into declarative (explicit) memory and a collection of nondeclarative (implicit) forms of memory that include habits, skills, priming, and simple forms of conditioning. These memory systems depend variously on the hippocampus and related structures in the parahippocampal gyrus, as well as on the amygdala, the striatum, cerebellum, and the neocortex. This work recounts the discovery of declarative and nondeclarative memory and then describes the nature of declarative memory, working memory, nondeclarative memory, and the relationship between memory systems., (Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.)

Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with perirhinal lesions were impaired and did not exhibit the normal preference for exploring the odd object. Notably, rats with hippocampal lesions exhibited the same impairment. Thus, the deficit is unlikely to illuminate functions attributed specifically to perirhinal cortex. Both lesion groups were able to acquire visual discriminations involving the same objects used in the oddity task. Patients with hippocampal damage or larger medial temporal lobe lesions were intact in a similar oddity task that allowed participants to explore objects quickly using eye movements. We suggest that humans were able to rely on an intact working memory capacity to perform this task, whereas rats (who moved slowly among the objects) needed to rely on long-term memory., (© 2015 Hales et al.; Published by Cold Spring Harbor Laboratory Press.)

The entorhinal cortex provides the primary cortical projections to the hippocampus, a brain structure critical for memory. However, it remains unclear how the precise firing patterns of medial entorhinal cortex (MEC) cells influence hippocampal physiology and hippocampus-dependent behavior. We found that complete bilateral lesions of the MEC resulted in a lower proportion of active hippocampal cells. The remaining active cells had place fields, but with decreased spatial precision and decreased long-term spatial stability. In addition, MEC rats were as impaired in the water maze as hippocampus rats, while rats with combined MEC and hippocampal lesions had an even greater deficit. However, MEC rats were not impaired on other hippocampus-dependent tasks, including those in which an object location or context was remembered. Thus, the MEC is not necessary for all types of spatial coding or for all types of hippocampus-dependent memory, but it is necessary for the normal acquisition of place memory.

Hippocampal damage has been thought to result in broad memory impairment. Recent studies in humans, however, have raised the possibility that recognition memory for faces might be spared. In five experiments we investigated face recognition in patients with hippocampal lesions (H) or large medial temporal lobe (MTL) lesions, including patients where neurohistological information was available. Recognition of novel faces was unequivocally intact in H patients but only at a short retention interval. Recognition memory for words, buildings, inverted faces, and famous faces was impaired. For MTL patients, recognition memory was impaired for all materials and across all retention intervals. These results indicate that structures other than the hippocampus, perhaps the perirhinal cortex, can support face recognition memory in H patients under some conditions. The fact that the faces were novel when recognition memory was intact does not fully account for our findings. We propose that the role of the hippocampus in recognition memory is related to how recognition decisions are accomplished. In typical recognition tasks, participants proceed by forming an association between a study item and the study list, and the recognition decision is later made based on whether participants believe the item was on the study list. We suggest that face recognition is an exception to this principle and that, at short retention intervals, participants can make their recognition decisions without making explicit reference to the study list. Important features of faces that might make face recognition exceptional are that they are processed holistically and are difficult to verbally label.