Neural correlates of successful encoding of semantically and phonologically mediated inter-item associations

This experiment investigated whether the neural correlates of inter-item associative encoding vary according to study task. At study, pairs of unrelated words were subjected to either semantic or phonological relational judgments. Test items comprised studied word pairs (intact), pairs comprised of words belonging to different study pairs (rearranged), and novel pairs. The test requirement was to discriminate between these different classes of test item. fMRI was employed to contrast the neural activity elicited by studied pairs that were correctly endorsed as intact on the later associative recognition test, as opposed to pairs for which associative information was unavailable. In contrast to prior findings for the encoding of single items, there was no evidence that the loci of subsequent associative memory effects varied according to study task. Instead, in both tasks, pairs that were later correctly endorsed as intact elicited enhanced activity in mid- and ventral regions of the left ventrolateral prefrontal cortex (VLPFC). These findings were accompanied by extensive task-invariant reversed subsequent memory effects in medial and lateral parietal and frontal cortices. The findings suggest that the left VLPFC may play a domain-general role in the encoding of item-item associations, and in addition highlight the importance of elucidating the functional significance of reversed subsequent memory effects.     

Transperceptual encoding and retrieval processes in memory: a PET study of visual and haptic objects

An important objective of functional neuroimaging research is to identify neuroanatomical correlates of memory processes such as encoding and retrieval. In typical studies directed at this goal, however, the to-be-remembered information has been presented in a single perceptual modality. Under these conditions it is not known whether the observed brain activity reflects the studied memory process as such or only the memory process in the given modality. The positron emission tomography (PET) study reported here was designed to identify brain regions involved in encoding and retrieval processes specific to visual and haptic modalities, as well as those common to the two modalities. These latter, common regions, were assumed to be associated with "transperceptual" encoding and retrieval processes. Abstract three-dimensional objects, difficult to describe verbally, served as to-be-remembered materials. A multivariate partial least squares analysis of the PET data revealed that transperceptual encoding processes activated right medial temporal lobe, superior prefrontal cortex bilaterally, and posterior inferior temporal gyrus bilaterally. Transperceptual recognition activations were observed in two right orbitofrontal regions and in anterior cingulate. These results provide initial evidence that some processes involved in memory encoding and retrieval operate beyond perceptual processes and in that sense are transperceptual.     

Putting names to faces: successful encoding of associative memories activates the anterior hippocampal formation

The ability to form associations between previously unrelated items of information, such as names and faces, is an essential aspect of episodic memory function. The neural substrate that determines success vs. failure in learning these associations remains to be elucidated. Using event-related functional MRI during the encoding of novel face-name associations, we found that successfully remembered face-name pairs showed significantly greater activation in the anterior hippocampal formation bilaterally and left inferior prefrontal cortex, compared to pairs that were forgotten. Functional connectivity analyses revealed significant correlated activity between the right and left hippocampus and neocortical regions during successful, but not attempted, encoding. These findings suggest that anterior regions of the hippocampal formation, in particular, are crucial for successful associative encoding and that the degree of coordination between hippocampal and neocortical activity may predict the likelihood of subsequent memory.     

Dissociating intentional learning from relative novelty responses in the medial temporal lobe

The establishment of a role for medial temporal lobe (MTL) structures in episodic memory has led to an investigative focus on the specific contributions and interactions between constituent MTL regions, including the hippocampus and surrounding medial temporal cortices. By dissociating an intentional stimulus-category learning condition from a passive viewing condition, we demonstrate, using fMRI, that novelty- and familiarity-driven responses in human anterior and posterior hippocampus, respectively, only occur during intentional learning. With increasing familiarity of stimulus-category associations, there is a shift in neuronal responses from anterior to posterior hippocampal regions. This anterior/posterior response gradient may reflect a weighting of functional hippocampal architecture related to encoding of novel and retrieval of familiar information. By contrast, perirhinal cortex is engaged by novel stimuli irrespective of task, highlighting this region as a component of a generic familiarity discrimination system. By introducing distinct stimulus types, we further demonstrate that these MTL responses are independent of stimulus complexity. Different patterns of activity for intentional learning vs. passive viewing indicate that intentional encoding/retrieval of stimulus-category associations and automatic novelty/familiarity assessment of stimuli are processed in anatomically dissociable neuronal ensembles within the MTL memory system.     

Distinct neural correlates of associative working memory and long-term memory encoding in the medial temporal lobe

Increasing evidence suggests a role for the hippocampus not only in long-term memory (LTM) but also in relational working memory (WM) processes, challenging the view of the hippocampus as being solely involved in episodic LTM. However, hippocampal involvement reported in some neuroimaging studies using "classical" WM tasks may at least partly reflect incidental LTM encoding. To disentangle WM processing and LTM formation we administered a delayed-match-to-sample associative WM task in an event-related fMRI study design. Each trial of the WM task consisted of four pairs of faces and houses, which had to be maintained during a delay of 10s. This was followed by a probe phase consisting of three consecutively presented pairs; for each pair participants were to indicate whether it matched one of the pairs of the encoding phase. After scanning, an unexpected recognition-memory (LTM) task was administered. Brain activity during encoding was analyzed based on WM and LTM performance. Hence, encoding-related activity predicting WM success in the absence of successful LTM formation could be isolated. Furthermore, regions critical for successful LTM formation for pairs previously correctly processed in WM were analyzed. Results showed that the left parahippocampal gyrus including the fusiform gyrus predicted subsequent accuracy on WM decisions. The right anterior hippocampus and left inferior frontal gyrus, in contrast, predicted successful LTM for pairs that were previously correctly classified in the WM task. Our results suggest that brain regions associated with higher-level visuo-perceptual processing are involved in successful associative WM encoding, whereas the anterior hippocampus and left inferior frontal gyrus are involved in successful LTM formation during incidental encoding.     

Effects of semantic relatedness on age-related associative memory deficits: the role of theta oscillations

Growing evidence suggests that age-related deficits in associative memory are alleviated when the to-be-associated items are semantically related. Here we investigate whether this beneficial effect of semantic relatedness is paralleled by spatio-temporal changes in cortical EEG dynamics during incidental encoding. Young and older adults were presented with faces at a particular spatial location preceded by a biographical cue that was either semantically related or unrelated. As expected, automatic encoding of face-location associations benefited from semantic relatedness in the two groups of age. This effect correlated with increased power of theta oscillations over medial and anterior lateral regions of the prefrontal cortex (PFC) and lateral regions of the posterior parietal cortex (PPC) in both groups. But better-performing elders also showed increased brain-behavior correlation in the theta band over the right inferior frontal gyrus (IFG) as compared to young adults. Semantic relatedness was, however, insufficient to fully eliminate age-related differences in associative memory. In line with this finding, poorer-performing elders relative to young adults showed significant reductions of theta power in the left IFG that were further predictive of behavioral impairment in the recognition task. All together, these results suggest that older adults benefit less than young adults from executive processes during encoding mainly due to neural inefficiency over regions of the left ventrolateral prefrontal cortex (VLPFC). But this associative deficit may be partially compensated for by engaging preexistent semantic knowledge, which likely leads to an efficient recruitment of attentional and integration processes supported by the left PPC and left anterior PFC respectively, together with neural compensatory mechanisms governed by the right VLPFC.     

An examination of the effects of stimulus type, encoding task, and functional connectivity on the role of right prefrontal cortex in recognition memory

Right anterior prefrontal cortex and other brain areas are active during memory retrieval but the role of prefrontal cortex and how it interacts with these other regions to mediate memory function remain unclear. To explore these issues we used positron emission tomography to examine the effects of stimulus material and encoding task on brain activity during visual recognition, assessing both task-related changes and functional connectivity. Words and pictures of objects were encoded using perceptual and semantic strategies, resulting in better memory for semantically encoded items. There was no significant effect of prior encoding strategy on brain activity during recognition. Right anterior prefrontal cortex was equally active during recognition of both types of stimuli irrespective of initial encoding strategy. Regions whose activity was positively correlated with activity in right anterior prefrontal cortex included widespread areas of prefrontal and inferior temporal cortices bilaterally. Activity in this entire network of regions was negatively correlated with recognition accuracy of semantically encoded items. These results suggest that initial encoding task has little impact on the set of brain regions that is active during subsequent recognition. Right anterior prefrontal cortex appears to be involved in retrieval mode, reflected in its equivalent activity across conditions differing in both stimulus type and encoding task, and also in retrieval effort, shown by the negative correlation between its functional connectivity and individual differences in recognition accuracy.     

The hippocampal region is involved in successful recognition of both remote and recent famous faces

There is currently a debate regarding the precise role of medial temporal regions in memory, in particular regarding the time scale of their involvement in conscious recollection of information stored in long-term memory. Using event-related fMRI, we have attempted to contribute to this debate by identifying brain regions associated with the successful recognition of famous faces from two different periods: "Old" faces of people who became famous in the 1960s-1970s and "Recent" faces of people who became famous in the 1990s. We demonstrate that the hippocampus is involved in the successful recognition of famous faces from both periods and does not appear to distinguish between these two periods. We also highlight a network of brain regions, including the left prefrontal cortex, the retrosplenial cortex, the temporo-parietal junction, the caudate and the right cerebellum, which is activated in association with successful recognition of famous faces. Finally, an analysis of the results obtained during a post hoc episodic recognition task shows the specific involvement of anterior hippocampus in the successful encoding of the unfamiliar faces, which were presented during the fame decision task, suggesting a functional distinction between anterior and posterior parts of the hippocampus, the former being specifically involved in successful episodic encoding and the latter being associated with successful retrieval of semantic information.     

Material-specific lateralization of memory encoding in the medial temporal lobe: blocked versus event-related design

Lesion-deficit studies have provided evidence for a functional dissociation between the left medial temporal lobe (MTL) mediating verbal memory encoding and right MTL mediating non-verbal memory encoding. While a small number of functional MRI studies have demonstrated similar findings, none has looked specifically for material-specific lateralization using subsequent memory effects. In addition, in many fMRI studies, encoding activity has been located in posterior MTL structures, at odds with lesion-deficit and positron emission tomography (PET) evidence. In this study, we used an event-related fMRI memory encoding paradigm to demonstrate a material-specific lateralization of encoding in the medial temporal lobes of ten healthy control subjects. Activation was left-lateralized for word encoding, bilateral for picture encoding, and right-lateralized for face encoding. Secondly, we demonstrated the locations of activations revealed using an event-related analysis to be more anterior than those revealed using a blocked analysis of the same data. This suggests that anterior MTL structures underlie memory encoding as judged by subsequent memory effects, and that more posterior activity detected in other fMRI studies is related to deficiencies of blocked designs in the analysis of memory encoding.     

Probing the transformation of discontinuous associations into episodic memory: an event-related fMRI study

Using event-related functional magnetic resonance imaging, we identified brain regions involved in storing associations of events discontinuous in time into long-term memory. Participants were scanned while memorizing item-triplets including simultaneous and discontinuous associations. Subsequent memory tests showed that participants remembered both types of associations equally well. First, by constructing the contrast between the subsequent memory effects for discontinuous associations and simultaneous associations, we identified the left posterior parahippocampal region, dorsolateral prefrontal cortex, the basal ganglia, posterior midline structures, and the middle temporal gyrus as being specifically involved in transforming discontinuous associations into episodic memory. Second, we replicated that the prefrontal cortex and the medial temporal lobe (MTL) especially the hippocampus are involved in associative memory formation in general. Our findings provide evidence for distinct neural operation(s) that supports the binding and storing discontinuous associations in memory. We suggest that top-down signals from the prefrontal cortex and MTL may trigger reactivation of internal representation in posterior midline structures of the first event, thus allowing it to be associated with the second event. The dorsolateral prefrontal cortex together with basal ganglia may support this encoding operation by executive and binding processes within working memory, and the posterior parahippocampal region may play a role in binding and memory formation.     

Emotional context during encoding of neutral items modulates brain activation not only during encoding but also during recognition

In general, encoding of neutral material includes the context in which the respective material is learned. The effect of emotional context on successfully encoded neutral material has been investigated only recently in few studies, but the main underlying mechanisms are still fairly unknown. In the present study, we investigated the effect of positive and negative emotional context on encoding and later recognition of neutral items. We could demonstrate that brain activation not only during encoding but also during recognition of neutral items depended on the emotional valence of the encoding context. Whereas activation of medial temporal lobe structures during encoding specifically predicted subsequent memory when learning appears in a positive emotional context, activation of the anterior temporal cortex in a region with afferent input to the amygdala predicted memory for material learned in negative context. Recognition of items encoded in positive emotional context revealed activation of hippocampal and medial prefrontal regions, recognition of items encoded in negative emotional context revealed activation of the caudate nucleus. We assume that our findings reflect the recruitment of different brain circuits depending on the emotional context during learning.     

Dissociating state and item components of recognition memory using fMRI

Cognitive functions such as memory retrieval involve a combination of state- and item-related processes. State-related processes are sustained throughout a task (e.g., "retrieval mode" associated with ongoing goals), whereas item-related processes are transient and allied to individual stimuli (e.g., "retrieval success" associated with the recovery of information from memory). The present study employed a mixed "blocked and event-related" experimental design to identify neural mechanisms that support state- and item-related processes during a recognition memory task. Subjects alternated between blocks of fixation and recognition memory (discriminating between old and new words). Critically, event-related procedures were embedded within the recognition blocks, including the jittering of sequential trials. This design ensures that the temporal profiles of state- and item-related activity differ and consequently renders them separable; without this procedure item-related activity would summate to produce a state-like response. Results suggest three classes of brain region support recognition memory, exhibiting: (1) predominantly transient activity (including regions in medial parietal, lateral parietal, and anterior left frontal cortex) reflecting item-related processing associated with "retrieval success," (2) predominantly sustained activity (including decreased activity in bilateral parahippocampal cortex) reflecting state-related processing associated with "retrieval mode," (3) concurrent sustained and transient activity (including regions in left middle frontal gyrus, bilateral frontal operculum, and medial frontal gyrus), reflecting a combination of state- and item-related processing. The present findings support the idea that recognition memory tasks are dependent upon a combination of state- and item-related processes that have dissociable neural correlates identifiable using fMRI. Moreover, the mixed "blocked and event-related" design employed here provides a general procedure for separating state- and item-related processes.     

Activation reduction in anterior temporal cortices during repeated recognition of faces of personal acquaintances

Repeated recognition of the face of a familiar individual is known to show semantic repetition priming effect. In this study, normal subjects were repeatedly presented faces of their colleagues, and the effect of repetition on the regional cerebral blood flow change was measured using positron emission tomography. They repeated a set of three tasks: the familiar-face detection (F) task, the facial direction discrimination (D) task, and the perceptual control (C) task. During five repetitions of the F task, familiar faces were presented six times from different views in a pseudorandom order. Activation reduction through the repetition of the F tasks was observed in the bilateral anterior (anterolateral to the polar region) temporal cortices which are suggested to be involved in the access to the long-term memory concerning people. The bilateral amygdala, the hypothalamus, and the medial frontal cortices, were constantly activated during the F tasks, and considered to be associated with the behavioral significance of the presented familiar faces. Constant activation was also observed in the bilateral occipitotemporal regions and fusiform gyri and the right medial temporal regions during perception of the faces, and in the left medial temporal regions during the facial familiarity detection task, which are consistent with the results of previous functional brain imaging studies. The results have provided further information about the functional segregation of the anterior temporal regions in face recognition and long-term memory.     

Processing of famous faces and medial temporal lobe event-related potentials: a depth electrode study

The present study aims at analyzing the modulation of two types of event-related potentials originating from the human medial temporal lobe, the rhinal AMTL-N400 and the hippocampal P600 by the processing of famous faces. Therefore, we used a face recognition paradigm in which subjects had to discriminate the faces of famous persons from the faces of non-famous persons. Eleven patients with unilateral medial temporal lobe epilepsy undergoing intrahippocampal depth electrode recording for presurgical evaluation participated in this study. Event-related potentials (ERP) were recorded while a sequence of famous and non-famous faces was presented to the patients. The presentation of each face was repeated. The faces evoked N400-like potentials (anterior medial temporal lobe N400, AMTL-N400) in the rhinal cortex and P600-like potentials in the hippocampus. ERPs elicited by famous faces were contrasted with ERPs elicited by non-famous faces. The first presentation of famous faces elicited an enhanced AMTL-N400 and an enhanced hippocampal P600 in comparison to the second presentations of the famous faces or the (first and second presentation of the) non-famous faces. This findings are discussed in terms of associative semantic memory processes and the retrieval of person-specific information from long-term memory stores triggered by the processing of famous faces.     

Electrophysiological evidence for the effect of interactive imagery on episodic memory: encouraging familiarity for non-unitized stimuli during associative recognition

Episodic memory depends upon multiple processes, including familiarity and recollection. Although associative recognition tasks are traditionally viewed as requiring recollection, recent research suggests a role for familiarity if to-be-remembered stimuli are perceived as unitized. Here we use event-related potentials (ERPs) to examine the relationship between stimulus properties and encoding strategy on the engagement of familiarity during associative recognition. Participants studied word pairs containing an association (e.g. traffic-jam) or an unassociated semantic relationship (e.g. violin-guitar), using either item or interactive imagery. At test, participants were required to recognize if word pairs were presented in the same pairing as study, were rearranged, or new. We hypothesized that adopting a strategy of interactive imagery during encoding (i.e. encouraging unitization) would enhance familiarity for unassociated word pairs but would have no effect on association pairs because they are already perceived as unitized. As expected, overall recognition performance was better for word pairs encoded with interactive imagery, and for association than semantic word pairs. ERPs recorded at test revealed an interaction between encoding strategy and stimulus properties. Association word pairs elicited similar bilateral frontal (familiarity) and left parietal (recollection) old/new effects following item and interactive imagery. By contrast, for semantic word pairs, the left parietal effect was equivalent across conditions, but the bilateral frontal effect was enhanced for the interactive imagery condition. The ERP results suggest that an encoding strategy of interactive imagery can enhance familiarity during associative recognition, but this effect is ultimately dependent on the properties of the stimuli to-be-remembered and the nature of the representations that underlie them.     

Reactivation of medial temporal lobe and occipital lobe during the retrieval of color information: A positron emission tomography study

It is widely accepted that memory traces of an event include various types of information about the content of the event and about the circumstances in which the individual experienced it. However, how these various types of information are stored and later retrieved is poorly understood. One hypothesis postulates that the retrieval of specific event information reactivates regions that were active during the encoding of this information, with the aid of binding functions of the medial temporal lobe (MTL) structures. We used positron emission tomography to identify the brain regions related to the encoding and retrieval of color information. Specifically, we assessed whether overlapping activity was found in both the MTL structures and color-related cortical regions during the encoding and retrieval of color information attached with meaningless shapes. During the study, subjects were asked to encode colored (red or green) and achromatic random shapes. At subsequent testing, subjects were presented with only achromatic shapes, which had been presented with or without colors during encoding, and were engaged in retrieval tasks of shapes and colors. Overlapping activity was found in the MTL and occipital lobe (the lingual and inferior occipital gyri) in the right hemisphere during the encoding and retrieval of meaningless shapes with color information compared with those without color information. Although there are some limitations to be considered, the present findings seem to support the view that the retrieval of specific event information is associated with reactivation of both the MTL structures and the regions involved during encoding of the information.     

Time-dependent neural activations related to recognition of people's names in emotional and neutral face-name associative learning: an fMRI study

Previous data have indicated that the left anterior temporal lobe contributes to the retrieval of familiar people's names, and that the extended network including the bilateral anterior temporal lobe plays an important role in the retrieval of newly learned people's names. However, there has been no direct evidence for time-dependent change in brain activation in face-name associations. In addition, previous studies have demonstrated that emotional information such as emotional faces may contribute to the organization of long-lasting episodic memory. In the present study, we investigated the activations related to the recognition of people's names in the context of emotional and neutral face-name associative learning. Before fMRI scanning, subjects learned face-name associations that included emotionally positive and neutral facial expressions. In immediate (5 min later) and delayed (2 weeks later) recognition with fMRI scanning, subjects were presented with studied faces with two names, and were asked to choose the correct associative name learned previously. Recognition-related activations were identified in the anterior part of bilateral temporal lobe for immediate recognition and only in the left temporal lobe for delayed recognition. Further analysis confirmed the time-dependent change in activation of the right anterior temporal lobe. Activation related to the processing of faces with positive expressions were observed in the left periamygdaloid area and temporal pole, although emotional information did not have an influence on task performance in this study. These findings suggest that the neural network involving the bilateral temporal lobe contributes to the retrieval of newly learned people's names, and that the left temporal lobe has a crucial and stable role in retrieval of people's names from faces, whereas the role of the right temporal lobe in retrieval of people's names may decrease with the time course.     

Verbal episodic memory impairment in Alzheimer's disease: a combined structural and functional MRI study

Anatomical and functional MRI images were acquired in a group of healthy elderly subjects (n = 11) and a group of patients diagnosed with probable Alzheimer's disease, from mild to moderate severity (n = 8). During functional sessions, verbal episodic Encoding and Recognition tasks were presented to subjects. Both groups were compared in terms of gray matter volume and cerebral activation. Furthermore, in the AD group, correlations between hippocampal gray matter volume and whole-brain activations were examined. When compared to healthy controls, AD patients presented significant gray matter atrophy as well as reduced activations during Encoding and Recognition in the medial temporal lobes and inferior parietal/superior temporal associative areas. In the same regions, the fMRI activity elicited by the Recognition task was positively correlated with hippocampal gray matter volume. Moreover, an increase of left prefrontal activity during Encoding and Recognition was observed in AD patients relative to controls and was correlated with memory performance. This additional activity elicited by episodic memory processes was not found to correlate with the degree of medial temporal atrophy in our group of patients. Our study shows that function in brain regions critical to episodic memory is altered in AD. During episodic Recognition, these functional changes may closely correlate with the progressive structural changes observed in the hippocampal region.     

Recognition memory for studied words is determined by cortical activation differences at encoding but not during retrieval

Prior work has shown that when responses to incidentally encoded words are sorted, subsequently remembered words elicit greater left prefrontal BOLD signal change relative to forgotten words. Similarly, low-frequency words elicit greater activation than high-frequency words in the same left prefrontal regions, contributing to their better subsequent memorability. This study examined the relative contribution of encoding and retrieval processes to the correct recognition of target words. A mixture of high- and low-frequency words was incidentally encoded. Scanning was performed at encoding as well as during retrieval. During encoding, greater activation in the left prefrontal and anterior cingulate regions predicted a higher proportion of hits for low-frequency words. However, data acquired during recognition showed that word frequency did not modulate activation in any of the areas tracking successful recognition. This result demonstrates that under some circumstances, the recognition of studied words is determined purely by processes that are active during encoding. In contrast to the finding for hits, activation associated with correctly rejected foils was modulated by word frequency, being higher for high-frequency words in the left lateral parietal and anterior prefrontal regions. These findings were replicated in two further experiments, one in which the number of test items at recognition was doubled and another where encoding strength for high-frequency words was varied (once vs. 10 times). These results indicate that word frequency modulates activity in the left lateral parietal and anterior prefrontal regions contingent on whether the item involved is correctly recognized as a target or a foil. This observation is consistent with a dual process account of episodic memory.     

Effective auditory-verbal encoding activates the left prefrontal and the medial temporal lobes: A generalization to illiterate subjects.

Recent event-related FMRI studies indicate that the prefrontal (PFC) and the medial temporal lobe (MTL) regions are more active during effective encoding than during ineffective encoding. The within-subject design and the use of well-educated young college students in these studies makes it important to replicate these results in other study populations. In this PET study, we used an auditory word-pair association cued-recall paradigm and investigated a group of healthy upper middle-aged/older illiterate women. We observed a positive correlation between cued-recall success and the regional cerebral blood flow of the left inferior PFC (BA 47) and the MTLs. Specifically, we used the cued-recall success as a covariate in a general linear model and the results confirmed that the left inferior PFC and the MTL are more active during effective encoding than during ineffective encoding. These effects were observed during encoding of both semantically and phonologically related word pairs, indicating that these effects are robust in the studied population, that is, reproducible within group. These results generalize the results of Brewer et al. (1998, Science 281, 1185-1187) and Wagner et al. (1998, Science 281, 1188-1191) to an upper middle aged/older illiterate population. In addition, the present study indicates that effective relational encoding correlates positively with the activity of the anterior medial temporal lobe regions.