Evidence for a specific role of the anterior hippocampal region in successful associative encoding

It has been well established that the hippocampal formation plays a critical role in the formation of memories. However, functional specialization within the hippocampus remains controversial. Using functional magnetic resonance imaging (fMRI) during a face-name associative encoding task, followed by a postscan recognition test for face memory and face-name pair memory, we investigated the roles of anterior and posterior hippocampal regions in successful encoding of associations and items. Whole-brain and region of interest (ROI) analyses revealed that the anterior hippocampal formation showed increased activation for subsequently remembered face-name associations compared with pairs that were forgotten. In contrast, the posterior hippocampal formation showed activation above baseline during attempted encoding of face-name pairs, but no evidence of differential activation based on subsequent memory. Furthermore, exploratory whole-brain analyses revealed that a parahippocampal region, most likely corresponding to perirhinal cortex, showed subsequent memory effects for faces. These data provide evidence for functional specialization within the hippocampal formation based on the associative nature of the stimuli and subsequent memory.     

Distinct hippocampal regions make unique contributions to relational memory

Neuroscientific research has shown that the hippocampus is important for binding or linking together the various components of a learning event into an integrated memory. In a prior study, we demonstrated that the anterior hippocampus is involved in memory for the relations among informational elements to a greater extent that it is involved in memory for individual elements (Giovanello et al., 2004. Hippocampus 14:5-8). In the current study, we extend those findings by further specifying the role of anterior hippocampus during relational memory retrieval. Specifically, anterior hippocampal activity was observed during flexible retrieval of learned associations, whereas posterior hippocampal activity was detected during reinstatement of study episodes. These findings suggest a functional dissociation across the long axis of human hippocampus based on the nature of the mnemonic process rather than the stage of memory processing or type of stimulus.     

Changing the criteria for old/new recognition judgments can modulate activity in the anterior hippocampus

Numerous functional magnetic resonance imaging (fMRI) studies have reported that the medial temporal lobe (MTL) is activated to a greater extent when subjects encounter novel items as compared with familiar ones. However, it remains unclear whether the novelty signals in the MTL are modulated by the criteria for old/new recognition judgments. In this study, we used fMRI to test our hypothesis that when subjects encounter items similar to previously encountered ones, the novelty signals in the MTL will differ depending on whether the subjects focus on the perceptual features or the semantic aspects of the items. The subjects studied a series of photographs and were later asked to make a recognition judgment of (a) Same items (items identical to those seen during encoding), (b) Similar items (items similar to but not identical to those seen during encoding), and (c) New items (unstudied items) in two types of tasks: Perceptual and Semantic. The subjects judged whether the items were perceptually identical to those seen during encoding in the Perceptual task and whether the items were semantically identical to those seen during encoding in the Semantic task. The left anterior hippocampus was activated when subjects were presented with New items relative to Same items in both tasks. In addition, the hippocampal activity in response to the Similar items was increased only in the Perceptual, but not the Semantic task. Our results indicate that the novelty signals in the hippocampus can be modulated by criteria for old/new recognition judgments.     

Hippocampal, parahippocampal and occipital-temporal contributions to associative and item recognition memory: an fMRI study

The temporal lobe regions involved in memory retrieval were examined using fMRI. During an associative recognition test, participants made memory judgments about the study color of previously presented drawings of objects, and during item recognition tests they made old/new judgments about previously studied objects or new objects. Associative recognition compared with old item recognition led to activations in bilateral hippocampal and parahippocampal regions, as well as in the left middle occipital gyrus. Old item recognition compared with new item recognition led to activation in the left middle occipital gyrus and the left middle temporal gyrus, and relative deactivations in bilateral hippocampal regions. The results indicate that partially distinct temporal lobe regions are involved during recognition memory for item and associative information.     

Neuronal activity in the hippocampus during delayed non-match to sample performance in rats: evidence for hippocampal processing in recognition memory.

Neuronal activity in the CA1 of rats was explored with regard to functional correlates of performance in an odor-guided continuous delayed non-match to sample task. Although different CA1 cells fired in association with each identifiable trial event, these analyses focused on cells that fired selectively during the period of odor cue sampling and response generation. The firing patterns of many of these cells reflected the match or non-match comparison between current and previous odor cues independent of the particular stimuli that composed those comparisons. Such cells were more prevalent in sessions when performance was highly accurate. Hippocampal cells did not demonstrate stimulus-evoked firing that persisted through the memory delay, nor did they fire differentially to session-novel vs. repeated odor presentations. These results suggest that the hippocampus contributes to recognition memory by processing comparisons between current information and representations of previous stimuli stored in parahippocampal and neocortical structures.     

Autobiographical memory in semantic dementia: A longitudinal fMRI study

Whilst patients with semantic dementia (SD) are known to suffer from semantic memory and language impairments, there is less agreement about whether memory for personal everyday experiences, autobiographical memory, is compromised. In healthy individuals, functional MRI (fMRI) has helped to delineate a consistent and distributed brain network associated with autobiographical recollection. Here we examined how the progression of SD affected the brain's autobiographical memory network over time. We did this by testing autobiographical memory recall in a SD patient, AM, with fMRI on three occasions, each one year apart, during the course of his disease. At the outset, his autobiographical memory was intact. This was followed by a gradual loss in recollective quality that collapsed only late in the course of the disease. There was no evidence of a temporal gradient. Initially, AM's recollection was supported by the classic autobiographical memory network, including atrophied tissue in hippocampus and temporal neocortex. This was subsequently augmented by up-regulation of other parts of the memory system, namely ventromedial and ventrolateral prefrontal cortex, right lateral temporal cortex, and precuneus. A final step-change in the areas engaged and the quality of recollection then preceded the collapse of autobiographical memory. Our findings inform theoretical debates about the role of the hippocampus and neocortical areas in supporting remote autobiographical memories. Furthermore, our results suggest it may be possible to define specific stages in SD-related memory decline, and that fMRI could complement MRI and neuropsychological measures in providing more precise prognostic and rehabilitative information for clinicians and carers.     

Medial temporal lobe activation during context-dependent relational processes in episodic retrieval: an fMRI study. Functional magnetic resonance imaging

Previous studies have reported that the medial temporal lobe (MTL) structures contribute to the processing of relations among multiple stimuli in episodic encoding. There have been few studies, however, on the episodic retrieval requiring processing of relations among multiple components that was involved in our events. We used functional magnetic resonance imaging (fMRI) to investigate neural activities during the retrieval of relations within an organized episode and the recognition of an episodic component. Healthy, normal participants memorized 50 four-scene comic strips before fMRI scanning. In the retrieval phase with fMRI scanning, participants were engaged in three tasks: a visual identification (VI) task, a story recall (SR) task, and a picture recognition (PRe) task. In the VI task, participants were asked to judge whether they could identify at least one female character in the two scenes presented vertically. In the SR task, participants were shown the first and last scenes from strips memorized previously and asked to judge whether or not the two scenes were from the same strip. In the PRe task, participants were shown two scenes and asked to judge whether they both belonged to the memorized scenes. The two contrasts of SR with VI and PRe with VI demonstrated some commonly activated areas, such as the bilateral middle frontal gyrus and cerebellum. More importantly, the SR task differentially activated the bilateral parahippocampal gyrus, whereas the PRe task differentially activated right prefrontal areas, including the inferior frontal and precentral gyri. The results suggest that the activity of the MTL structures may be strongly associated with episodic memory retrieval requiring context-dependent relational processing.     

EEG and fMRI evidence for autobiographical memory reactivation in empathy

Empathy relies on the ability to mirror and to explicitly infer others'' inner states. Theoretical accounts suggest that memories play a role in empathy, but direct evidence of reactivation of autobiographical memories (AM) in empathy is yet to be shown. We addressed this question in two experiments. In Experiment 1, electrophysiological activity (EEG) was recorded from 28 participants. Participants performed an empathy task in which targets for empathy were depicted in contexts for which participants either did or did not have an AM, followed by a task that explicitly required memory retrieval of the AM and non‐AM contexts. The retrieval task was implemented to extract the neural fingerprints of AM and non‐AM contexts, which were then used to probe data from the empathy task. An EEG pattern classifier was trained and tested across tasks and showed evidence for AM reactivation when participants were preparing their judgement in the empathy task. Participants self‐reported higher empathy for people depicted in situations they had experienced themselves as compared to situations they had not experienced. A second independent fMRI experiment replicated this behavioural finding and showed increased activation for AM compared to non‐AM in the brain networks underlying empathy: precuneus, posterior parietal cortex, superior and inferior parietal lobule, and superior frontal gyrus. Together, our study reports behavioural, electrophysiological, and fMRI evidence that robustly supports AM reactivation in empathy.     

Gradual acquisition of visuospatial associative memory representations via the dorsal precuneus

Activation of parietal cortex structures like the precuneus is commonly observed during explicit memory retrieval, but the role of parietal cortices in encoding has only recently been appreciated and is still poorly understood. Considering the importance of the precuneus in human visual attention and imagery, we aimed to assess a potential role for the precuneus in the encoding of visuospatial representations into long‐term memory. We therefore investigated the acquisition of constant versus repeatedly shuffled configurations of icons on background images over five subsequent days in 32 young, healthy volunteers. Functional magnetic resonance imaging was conducted on Days 1, 2, and 5, and persistent memory traces were assessed by a delayed memory test after another 5 days. Constant compared to shuffled configurations were associated with significant improvement of position recognition from Day 1 to 5 and better delayed memory performance. Bilateral dorsal precuneus activations separated constant from shuffled configurations from Day 2 onward, and coactivation of the precuneus and hippocampus dissociated recognized and forgotten configurations, irrespective of condition. Furthermore, learning of constant configurations elicited increased functional coupling of the precuneus with dorsal and ventral visual stream structures. Our results identify the precuneus as a key brain structure in the acquisition of detailed visuospatial information by orchestrating a parieto–occipito–temporal network.     

Differential development of relational memory and pattern separation

Researchers have taken a number of different approaches in their exploration of hippocampal function. One approach seeks to describe hippocampal function by probing the memory representations that the hippocampus supports. Another approach focuses on the role of the hippocampus in pattern separation and completion. Each of these approaches to understanding hippocampal function utilizes a distinct set of specialized tasks, and both of these task sets are known to be sensitive to changes in hippocampal function with age and disease status. But the question remains whether the tasks utilized in these two approaches tap into the same aspects of hippocampal function. We explored this question in the context of hippocampal development. Preadolescent children (N = 73) and young adults (N = 41) completed an identical battery of cognitive tasks consisting of a spatial reconstruction relational memory task, the mnemonic similarity task (MST)—an object‐based pattern separation task, and a novel hybrid task—the Object Discrimination and Distribution (ODD) Task—designed to integrate and simultaneously tax pattern separation and spatial relational memory. Children did not demonstrate impairments in lure discrimination relative to young adults on either the object‐based pattern separation task or for aspects of the ODD task that required pattern separation in the absence of relational memory demands but performed more poorly across aspects of tasks that required relational binding.     

Effects of aging on true and false memory formation: an fMRI study

Compared to young, older adults are more likely to forget events that occurred in the past as well as remember events that never happened. Previous studies examining false memories and aging have shown that these memories are more likely to occur when new items share perceptual or semantic similarities with those presented during encoding. It is theorized that decreased item-specific encoding and increased gist encoding contribute to these age differences in memory performance. The current study used a modified version of the Deese–Roediger–McDermott (DRM) paradigm to investigate the neural correlates of true and false memory encoding. Results indicated that, compared to young, older adults showed reduced activity in medial temporal lobes (MTL), left ventrolateral prefrontal cortex (VLPFC), and visual cortices associated with subsequent true memories. Despite these decreases older adults showed increased activity in right VLPFC and left superior temporal gyrus (STG) for subsequent true memories. Age-related increases in STG were also associated with subsequent false memories. Results support the theory that older adults engage in less item-specific encoding and greater gist encoding, and that these increases in gist encoding support both subsequent true and false memories. Furthermore, results extend findings of reduced frontal asymmetry in aging, often found in block designs, to the subsequent memory paradigm. Results suggest that greater bilateral frontal activity during encoding in aging are not just task-related, but may be associated with subsequent successful memory performance.     

Associative memory encoding and recognition in schizophrenia: an event-related fMRI study.

BACKGROUND: We used an event-related functional Magnetic Resonance Imaging (fMRI) approach to examine the neural basis of the selective associative memory deficit in schizophrenia. METHODS: Fifteen people with schizophrenia and 18 controls were scanned during a pair and item memory encoding and recognition task. During encoding, subjects studied items and pairs of visual objects. In a subsequent retrieval task, participants performed an item recognition memory test (old/new decisions) and an associative recognition test (intact/rearranged decisions). The fMRI analysis of the recognition data was restricted to correct items only and a random effects model was used. RESULTS: At the behavioral level, both groups performed equally well on item recognition, whereas people with schizophrenia demonstrated lower performance on associative recognition relative to the control group. At the brain level, the comparison between associative and item encoding revealed greater activity in the control group in the left prefrontal cortex and cingulate gyrus relative to the schizophrenia group. During recognition, greater left dorsolateral prefrontal and right inferior prefrontal activations were observed in the control group relative to the schizophrenia group. CONCLUSION: This fMRI study implicates the prefrontal cortex among other brain regions as the basis for the selective associative memory encoding and recognition deficit seen in schizophrenia.     

The influence of emotional distraction on verbal working memory: an fMRI investigation comparing individuals with schizophrenia and healthy adults

The ability to maintain information over short periods of time (i.e., working memory) is critically important in a variety of cognitive functions including language, planning, and decision-making. Recent functional Magnetic Resonance Imaging (fMRI) research with healthy adults has shown that brain activations evoked during the delay interval of working memory tasks can be reduced by the presentation of distracting emotional events, suggesting that emotional events may take working-memory processes momentarily offline. Both executive function and emotional processing are disrupted in schizophrenia, and here we sought to elucidate the effect of emotional distraction upon brain activity in schizophrenic and healthy adults performing a verbal working memory task. During the delay period between the memoranda and memory probe items, emotional and neutral distractors differentially influenced brain activity in these groups. In healthy adults, the hemodynamic response from posterior cingulate, orbital frontal cortex, and the parietal lobe strongly differentiated emotional from neutral distractors. In striking contrast, schizophrenic adults showed no significant differences in brain activation when processing emotional and neutral distractors. Moreover, the influence of emotional distractors extended into the memory probe period in healthy, but not schizophrenic, adults. The results suggest that although emotional items are highly salient for healthy adults, emotional items are no more distracting than neutral ones to individuals with schizophrenia.     

Evidence for a virtual human analog of a rodent relational memory task: a study of aging and fMRI in young adults

A radial maze concurrent spatial discrimination learning paradigm consisting of two stages was previously designed to assess the flexibility property of relational memory in mice, as a model of human declarative memory. Aged mice and young adult mice with damage to the hippocampus, learned accurately Stage 1 of the task which required them to learn a constant reward location in a specific set of arms (i.e., learning phase). In contrast, they were impaired relative to healthy young adult mice in a second stage when faced with rearrangements of the same arms (i.e., flexibility probes). This mnemonic inflexibility in Stage 2 is thought to derive from insufficient relational processing by the hippocampus during initial learning (Stage 1) which favors stimulus-response learning, a form of procedural learning. This was proposed as a model of the selective declarative and relational memory decline classically described in elderly people. As a first step to examine the validity of this model, we adapted this protocol to humans using a virtual radial-maze. (1) We showed that performance in the flexibility probes in young and older adults positively correlated with performance in a wayfinding task, suggesting that our paradigm assesses relational memory. (2) We demonstrated that older healthy participants displayed a deficit in the performance of the flexibility probes (Stage 2), similar to the one previously seen in aged mice. This was associated with a decline in the wayfinding task. (3) Our fMRI data in young adults confirmed that hippocampal activation during early discrimination learning in Stage 1 correlated with memory flexibility in Stage 2, whereas caudate nucleus activation in Stage 1 negatively correlated with subsequent flexibility. By enabling relational memory assessment in mice and humans, our radial-maze paradigm provides a valuable tool for translational research.     

Lateral entorhinal cortex is necessary for associative but not nonassociative recognition memory

The lateral entorhinal cortex (LEC) provides one of the two major input pathways to the hippocampus and has been suggested to process the nonspatial contextual details of episodic memory. Combined with spatial information from the medial entorhinal cortex it is hypothesised that this contextual information is used to form an integrated spatially selective, context‐specific response in the hippocampus that underlies episodic memory. Recently, we reported that the LEC is required for recognition of objects that have been experienced in a specific context (Wilson et al. (2013) Hippocampus 23:352‐366). Here, we sought to extend this work to assess the role of the LEC in recognition of all associative combinations of objects, places and contexts within an episode. Unlike controls, rats with excitotoxic lesions of the LEC showed no evidence of recognizing familiar combinations of object in place, place in context, or object in place and context. However, LEC lesioned rats showed normal recognition of objects and places independently from each other (nonassociative recognition). Together with our previous findings, these data suggest that the LEC is critical for associative recognition memory and may bind together information relating to objects, places, and contexts needed for episodic memory formation. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

Regional brain activations predicting subsequent memory success: an event-related fMRI study of the influence of encoding tasks

We determined the brain regions that were differentially sensitive to two, randomly inter-mixed tasks: Deep Encoding, in which subjects processed items according to their meaning (is the word pleasant or unpleasant?) and Shallow Encoding, in which items were processed according to two underlined letters in the word (are the letters in alphabetical order?). The former task was associated with activations in a set of brain regions including left lateral prefrontal cortex (PFC) and left medial temporal cortex. The latter showed relatively greater activation in right PFC. Both findings are consistent with predictions made on the basis of previous functional neuroimaging work. Following scanning, each subject underwent a recognition memory task. The results of these provided the basis for a further sub-division of encoding events, according to whether they were predictive of subsequent recognition success or not. Unsurprisingly, recognition performance was greater for words that had been deeply encoded. For both encoding conditions, words that were subsequently recognised were associated with greater activation in a sub-set of regions identified by the deep versus shallow contrast. These included left PFC and medial temporal regions. In left PFC this performance-predicting activation was significantly greater for the deep encoding condition. Our results support previous studies suggesting a role for left PFC and medial temporal cortex in episodic memory encoding. They provide more evidence, too, for a less consistent finding: the interaction between the encoding task and the success of subsequent recognition.     

Understanding medial temporal activation in memory tasks: evidence from fMRI of encoding and recognition in a case of transient global amnesia

We used fMRI to examine the activation patterns of patient AE during encoding and recognition of visual scenes during an episode of transient global amnesia (TGA) and 3 months later. Controls (n = 5) showed bilateral (R > L) activation in parahippocampal and fusiform gyri during encoding and right-sided activation in the same regions associated with recognition of previously viewed scenes. AE showed a similar pattern at follow-up. During acute TGA, when performance was profoundly impaired, AE showed no medial temporal activation associated with encoding of new scenes or recognition of old scenes. In both contrasts, the percent signal change in relevant medial temporal regions was more than three standard deviations below the control sample mean. She did, however, show striking bilateral hippocampal activation for recognition attempts (old + new scenes > baseline) even though retrieval was unsuccessful (55% recognition accuracy). This finding was unique to AE on this occasion. This is the first study to document normalization of both encoding and recognition activation patterns in TGA. Furthermore, the strong hippocampal activation during unsuccessful retrieval highlights important issues in interpreting memory-related activations, particularly in dysfunctional systems.     

Neural correlates of recognition memory for emotional faces and scenes

We examined the influence of emotional valence and type of item to be remembered on brain activity during recognition, using faces and scenes. We used multivariate analyses of event-related fMRI data to identify whole-brain patterns, or networks of activity. Participants demonstrated better recognition for scenes vs faces and for negative vs neutral and positive items. Activity was increased in extrastriate cortex and inferior frontal gyri for emotional scenes, relative to neutral scenes and all face types. Increased activity in these regions also was seen for negative faces relative to positive faces. Correct recognition of negative faces and scenes (hits vs correct rejections) was associated with increased activity in amygdala, hippocampus, extrastriate, frontal and parietal cortices. Activity specific to correctly recognized emotional faces, but not scenes, was found in sensorimotor areas and rostral prefrontal cortex. These results suggest that emotional valence and type of visual stimulus both modulate brain activity at recognition, and influence multiple networks mediating visual, memory and emotion processing. The contextual information in emotional scenes may facilitate memory via additional visual processing, whereas memory for emotional faces may rely more on cognitive control mediated by rostrolateral prefrontal regions.