Spatial and temporal episodic memory retrieval recruit dissociable functional networks in the human brain

Imaging, electrophysiological studies, and lesion work have shown that the medial temporal lobe (MTL) is important for episodic memory; however, it is unclear whether different MTL regions support the spatial, temporal, and item elements of episodic memory. In this study we used fMRI to examine retrieval performance emphasizing different aspects of episodic memory in the context of a spatial navigation paradigm. Subjects played a taxi-driver game ("yellowcab"), in which they freely searched for passengers and delivered them to specific landmark stores. Subjects then underwent fMRI scanning as they retrieved landmarks, spatial, and temporal associations from their navigational experience in three separate runs. Consistent with previous findings on item memory, perirhinal cortex activated most strongly during landmark retrieval compared with spatial or temporal source information retrieval. Both hippocampus and parahippocampal cortex activated significantly during retrieval of landmarks, spatial associations, and temporal order. We found, however, a significant dissociation between hippocampal and parahippocampal cortex activations, with spatial retrieval leading to greater parahippocampal activation compared with hippocampus and temporal order retrieval leading to greater hippocampal activation compared with parahippocampal cortex. Our results, coupled with previous findings, demonstrate that the hippocampus and parahippocampal cortex are preferentially recruited during temporal order and spatial association retrieval--key components of episodic "source" memory.     

Imaging recollection and familiarity in the medial temporal lobe: a three-component model

The medial temporal lobe (MTL) plays a crucial role in supporting memory for events, but the functional organization of regions in the MTL remains controversial, especially regarding the extent to which different subregions support recognition based on familiarity or recollection. Here we review results from functional neuroimaging studies showing that, whereas activity in the hippocampus and posterior parahippocampal gyrus is disproportionately associated with recollection, activity in the anterior parahippocampal gyrus is disproportionately associated with familiarity. The results are consistent with the idea that the parahippocampal cortex (located in the posterior parahippocampal gyrus) supports recollection by encoding and retrieving contextual information, whereas the hippocampus supports recollection by associating item and context information. By contrast, perirhinal cortex (located in the anterior parahippocampal gyrus) supports familiarity by encoding and retrieving specific item information. We discuss the implications of a 'binding of item and context' (BIC) model for studies of recognition memory. This model argues that there is no simple mapping between MTL regions and recollection and familiarity, but rather that the involvement of MTL regions in these processes depends on the specific demands of the task and the type of information involved. We highlight several predictions for future imaging studies that follow from the BIC model.     

Distinct roles for medial temporal lobe structures in memory for objects and their locations

The ability to learn and retain novel information depends on a system of structures in the medial temporal lobe (MTL) including the hippocampus and the surrounding entorhinal, perirhinal, and parahippocampal cortices. Damage to these structures produces profound memory deficits; however, the unique contribution to memory of each of these structures remains unclear. Here we have used functional magnetic resonance imaging (fMRI) to determine whether the perirhinal and parahippocampal cortices show differential memory-related activity. Based on the distinct patterns of cortical input to these two areas, we reasoned that these structures might show differential activity for spatial and object recognition memory. In each of 11 subjects, we found that the perirhinal cortex was active during both spatial and object memory encoding, while the anterior parahippocampal cortex was active only during spatial encoding. These data support the idea that MTL structures make distinct contributions to recognition memory performance.     

The role of medial temporal lobe in item recognition and source recollection of emotional stimuli

Recent neuroimaging results suggest that distinct regions within the medial temporal lobe (MTL) may differentially support the episodic encoding of item and relational information for nonemotional stimuli (for a review, see Davachi, 2006). The present study was designed to assess whether these findings generalize to emotional stimuli. Behaviorally, we found that emotion reduced item recognition accuracy but did not reliably affect relational memory. fMRI analyses revealed that neutral and emotional words elicited distinct activation patterns within MTL regions predictive of subsequent memory. Consistent with previous findings for neutral words, hippocampal activation predicted later relational memory, whereas activation in the perirhinal cortex predicted successful item recognition. However, for emotional words, activation in the amygdala, hippocampus, and posterior parahippocampal cortex predicted item recognition only. These data suggest that MTL regions differentially support encoding of neutral and emotional stimuli.     

Content-specific source encoding in the human medial temporal lobe

Although the medial temporal lobe (MTL) is known to be essential for episodic encoding, the contributions of individual MTL subregions remain unclear. Data from recognition memory studies have provided evidence that the hippocampus supports relational encoding important for later episodic recollection, whereas the perirhinal cortex has been linked with encoding that supports later item familiarity. However, extant data also strongly implicate the perirhinal cortex in object processing and encoding, suggesting that perirhinal processes may contribute to later episodic recollection of object source details. To investigate this possibility, encoding activation in MTL subregions was analyzed on the basis of subsequent memory outcome while participants processed novel scenes paired with 1 of 6 repeating objects. Specifically, encoding activation correlating with later successful scene recognition memory was evaluated against that of source recollection for the object paired with the scene during encoding. In contrast to studies reporting a link between perirhinal cortex and item familiarity, it was found that encoding activation in the right perirhinal cortex correlates with successful recollection of the paired object. Furthermore, other MTL subregions also exhibited content-specific source encoding patterns of activation, suggesting that MTL subsequent memory effects are sensitive to stimulus category.     

A mini-review of fMRI studies of human medial temporal lobe activity associated with recognition memory.

This review considers event-related functional magnetic resonance imaging (fMRI) studies of human recognition memory that have or have not reported activations within the medial temporal lobes (MTL). For comparisons both between items at study (encoding) and between items at test (recognition), MTL activations are characterized as left/right, anterior/posterior, and hippocampus/surrounding cortex, and as a function of the stimulus material and relevance of item/source information. Though no clear pattern emerges, there are trends suggesting differences between item and source information, and verbal and spatial information, and a role for encoding processes during recognition tests. Important future directions are considered.     

A mini-review of fMRI studies of human medial temporal lobe activity associated with recognition memory

This review considers event-related functional magnetic resonance imaging (fMRI) studies of human recognition memory that have or have not reported activations within the medial temporal lobes (MTL). For comparisons both between items at study (encoding) and between items at test (recognition), MTL activations are characterized as left/right, anterior/posterior, and hippocampus/surrounding cortex, and as a function of the stimulus material and relevance of item/source information. Though no clear pattern emerges, there are trends suggesting differences between item and source information, and verbal and spatial information, and a role for encoding processes during recognition tests. Important future directions are considered.     

Neurophysiology of successful encoding and retrieval of source memory

Event-related potentials were recorded during encoding, to identify whether brain activity predicts subsequent retrieval of spatial source information, and during retrieval, to investigate the neural correlates of successful and unsuccessful spatial context recollection. The amplitude registered during encoding for study items that were later recognized and assigned a correct source judgment was more positive than the amplitude for recognized items given incorrect source judgments; this difference started 480 msec poststimulus, predominantly at central and anterior sites. During retrieval, the waveform was more positive from 250 to 1,600 msec poststimulus when the brain had retrieved episodic information successfully than when it had failed. These findings indicate that brain electrical activity recorded during the first presentation of an item within its context predicts the subsequent retrieval of the specific spatial context. During retrieval, brain activity differed quantitatively at anterior sites and qualitatively at posterior sites according to the accuracy of source memory.     

An fMRI study of long-term everyday memory using SenseCam

We used a novel automatic camera, SenseCam, to investigate recognition memory for real-life events at a 5-month retention interval. Using fMRI we assessed recollection and familiarity memory using the remember/know procedure. Recollection evoked no medial temporal lobe (MTL) activation compared to familiarity and new responses. Instead, recollection activated diverse regions in neocortex including medial prefrontal cortex. We observed decreased activation in anterior hippocampus/ anterior parahippocampal gyrus (aPHG) at 5 months compared to a 36-hour retention interval. Familiarity was associated with greater activation in aPHG and posterior parahippocampal gyrus (pPHG) than recollection and new responses. Familiarity activation decreased over time in anterior hippocampus/aPHG and posterior hippocampus/pPHG. The engagement of neocortical regions such as medial prefrontal cortex at a 5-month delay, together with the reduced MTL activation at 5 months relative to at 36 hours is in line with the assumptions of Consolidation theory. SenseCam provides a valuable technique for assessing the processes that underlie remote everyday recognition memory.     

The effects of unitization on familiarity-based source memory: testing a behavioral prediction derived from neuroimaging data

Performance on tests of source memory is typically based on recollection of contextual information associated with an item. However, recent neuroimaging results have suggested that the perirhinal cortex, a region thought to support familiarity-based item recognition, may support source attributions if source information is encoded as a feature of the relevant item (i.e., "unitized"). The authors hypothesized that familiarity may contribute to source memory performance if item and source information are unitized during encoding, whereas performance may rely more heavily on recollection if source information is encoded as an arbitrary contextual association. Three source recognition experiments examining receiver operating characteristics and response deadline performance indicated that familiarity makes a greater contribution to source memory if source and item information are unitized during encoding. These findings suggest that familiarity can contribute to source recognition and that its contribution depends critically on the way item and source information are initially processed.     

Modulation of retrieval processing reflects accuracy of emotional source memory

There is considerable evidence that encoding and consolidation of memory are modulated by emotion, but the retrieval of emotional memories is not well characterized. Here we manipulated the emotional context with which affectively neutral stimuli were associated during encoding, allowing us to examine neural activity associated with retrieval of emotional memories without confounding the emotional attributes of cue items and the retrieved context. Using a source memory procedure we were also able to compare how retrieval processing was modulated when the emotional encoding context was recollected or not. An interaction between emotional encoding context and accuracy of source memory revealed that successful retrieval of emotional context was associated with activity in left amygdala, and a left frontotemporal network including anterior insula, prefrontal cortex and cingulate. In contrast, when contextual retrieval was unsuccessful, items encoded in emotional contexts elicited enhanced activity in right amygdala and a right-lateralized network that included extrastriate visual areas. These findings indicate distinct effects of emotion on successful and unsuccessful retrieval of source information, including lateralization of amygdala responses.     

Dissociable contributions within the medial temporal lobe to encoding of object-location associations

The crucial role of the medial temporal lobe (MTL) in episodic memory is well established. Although there is little doubt that its anatomical subregions-the hippocampus, peri-, entorhinal and parahippocampal cortex (PHC)-contribute differentially to mnemonic processes, their specific functions in episodic memory are under debate. Data from animal, human lesion, and neuroimaging studies suggest somewhat contradictory perspectives on this functional specialization: a general participation in declarative memory, an exclusive involvement in associative mnemonic processes, and a specific contribution to spatial memory are reported for the hippocampus, adjacent cortices, and the PHC. A functional lateralization in humans dependent on the verbalizability of the material is also discussed herein. To further elucidate the differential contributions of the various MTL subregions to encoding, we employed an object-location association memory paradigm. The memory for each of the studied associations was tested twice: by the object, and by the location serving as retrieval cue. The memory accuracy in response to both cue types was also assessed parametrically. Brain activity during encoding which leads to different degrees of subsequent memory accuracy under the two retrieval conditions was compared. We found the bilateral posterior PHC to participate in encoding of both the object associated with a location and the location associated with an object. In contrast, activity in an area in the left anterior PHC and the right anterior MTL was only correlated with the memory for the location associated with an object.     

The role of the perirhinal cortex and hippocampus in learning, memory, and perception.

One traditional and long-held view of medial temporal lobe (MTL) function is that it contains a system of structures that are exclusively involved in memory, and that the extent of memory loss following MTL damage is simply related to the amount of MTL damage sustained. Indeed, human patients with extensive MTL damage are typically profoundly amnesic whereas patients with less extensive brain lesions centred upon the hippocampus typically exhibit only moderately severe anterograde amnesia. Accordingly, the latter observations have elevated the hippocampus to a particularly prominent position within the purported MTL memory system. This article reviews recent lesion studies in macaque monkeys in which the behavioural effects of more highly circumscribed lesions (than those observed to occur in human patients with MTL lesions) to different subregions of the MTL have been examined. These studies have reported new findings that contradict this concept of a MTL memory system. First, the MTL is not exclusively involved in mnemonic processes; some MTL structures, most notably the perirhinal cortex, also contribute to perception. Second, there are some forms of memory, including recognition memory, that are not always affected by selective hippocampal lesions. Third, the data support the idea that regional functional specializations exist within the MTL. For example, the macaque perirhinal cortex appears to be specialized for processing object identity whereas the hippocampus may be specialized for processing spatial and temporal relationships.     

The role of the perirhinal cortex and hippocampus in learning, memory, and perception

One traditional and long-held view of medial temporal lobe (MTL) function is that it contains a system of structures that are exclusively involved in memory, and that the extent of memory loss following MTL damage is simply related to the amount of MTL damage sustained. Indeed, human patients with extensive MTL damage are typically profoundly amnesic whereas patients with less extensive brain lesions centred upon the hippocampus typically exhibit only moderately severe anterograde amnesia. Accordingly, the latter observations have elevated the hippocampus to a particularly prominent position within the purported MTL memory system. This article reviews recent lesion studies in macaque monkeys in which the behavioural effects of more highly circumscribed lesions (than those observed to occur in human patients with MTL lesions) to different subregions of the MTL have been examined. These studies have reported new find-ings that contradict this concept of a MTL memory system. First, the MTL is not exclusively involved in mnemonic processes; some MTL structures, most notably the perirhinal cortex, also contribute to perception. Second, there are some forms of memory, including recognition memory, that are not always affected by selective hippocampal lesions. Third, the data support the idea that regional functional specializations exist within the MTL. For example, the macaque perirhinal cortex appears to be specialized for processing object identity whereas the hippocampus may be specialized for processing spatial and temporal relationships.     

The consolidation of object and context recognition memory involve different regions of the temporal lobe

These experiments investigated the involvement of several temporal lobe regions in consolidation of recognition memory. Anisomycin, a protein synthesis inhibitor, was infused into the hippocampus, perirhinal cortex, insular cortex, or basolateral amygdala of rats immediately after the sample phase of object or object-in-context recognition memory training. Anisomycin infused into perirhinal or insular cortices blocked long-term (24 h), but not short-term (90 min) object recognition memory. Infusions into the hippocampus or amygdala did not impair object recognition memory. Anisomycin infused into the hippocampus blocked long-term, but not short-term object-in-context recognition memory, whereas infusions administered into the perirhinal cortex, insular cortex, or amygdala did not affect object-in-context recognition memory. These results clearly indicate that distinct regions of the temporal lobe are differentially involved in long-term object and object-in-context recognition memory. Whereas perirhinal and insular cortices are required for consolidation of familiar objects, the hippocampus is necessary for consolidation of contextual information of recognition memory. Altogether, these results suggest that temporal lobe structures are differentially involved in recognition memory consolidation.     

Bi-hemispheric engagement in the retrieval of autobiographical episodes

Functional magnetic resonance imaging (fMRI) was used to study the neural correlates of neutral, stressful, negative and positive autobiographical memories. The brain activity produced by these different kinds of episodic memory did not differ significantly, but a common pattern of activation for different kinds of autobiographical memory was revealed that included (1) largely bilateral portions of the medial and superior temporal lobes, hippocampus and parahippocampus, (2) portions of the ventral, medial, superior and dorsolateral prefrontal cortex, (3) the anterior and posterior cingulate, including the retrosplenial, cortex, (4) the parietal cortex, and (5) portions of the cerebellum. The brain regions that were mainly activated constituted an interactive network of temporal and prefrontal areas associated with structures of the extended limbic system. The main bilateral activations with left-sided preponderance probably reflected reactivation of complex semantic and episodic self-related information representations that included previously experienced contexts. In conclusion, the earlier view of a strict left versus right prefrontal laterality in the retrieval of semantic as opposed to episodic autobiographical memory, may have to be modified by considering contextual variables such as task demands and subject variables. Consequently, autobiographical memory integration should be viewed as based on distributed bi-hemispheric neural networks supporting multi-modal, emotionally coloured components of personal episodes.     

Electrophysiological correlates of encoding and retrieving emotional events

This study examined the impact of emotional content on encoding and retrieval processes. Event-related potentials were recorded in a source recognition memory task. During encoding, a posterior positivity for positive and negative pictures (250-450 ms) that presumably reflects attentional capturing of emotionally valenced stimuli was found. Additionally, positive events, which were also rated as less arousing than negative events, gave rise to anterior and posterior slow wave activity as compared with neutral and negative events and also showed enhanced recognition memory. It is assumed that positive low-arousing events enter controlled and elaborated encoding processes that are beneficial for recognition memory performance. The high arousal of negative events may interfere with controlled encoding mechanisms and attenuate item recognition and the quality of remembering. Moreover, topographically distinct late posterior negativities were obtained for the retrieval of the context features location and time that support the view that this component reflects processes in service of reconstructing the study episode by binding together contextual details with an item and that varies with the kind of episodic detail to be retrieved.     

Decreased parahippocampal activity in associative priming: evidence from an event-related fMRI study

In recent years, there has been intense debate on the neural basis of associative priming, particularly on the role of the medial temporal lobe (MTL) in retrieving associative information without awareness. In this study, event-related fMRI was used while healthy subjects performed a perceptual identification task on briefly presented unrelated word pairs and an associative recognition memory task. Contamination of priming by explicit memory was successfully controlled, as associative priming and explicit memory were dissociated on the behavioral level. The fMRI results showed a functional dissociation within the MTL with respect to associative priming effects. The right parahippocampal cortex, but not the hippocampus, showed decreased activation for old vs. new pairs and old vs. recombined pairs (associative priming). The bilateral hippocampus and the right parahippocampal cortex were involved in explicit associative memory. These data provide evidence that subregions of the MTL participate in associative priming even when explicit involvement was controlled. Thus, different regions within the MTL play distinct roles in explicit and implicit associative memory.     

Neural correlates of autobiographical memory retrieval in children and adults

Autobiographical memory (AM) is a critically important form of memory for life events that undergoes substantial developmental changes from childhood to adulthood. Relatively little is known regarding the functional neural correlates of AM retrieval in children as assessed with fMRI, and how they may differ from adults. We investigated this question with 14 children ages 8–11 years and 14 adults ages 19–30 years, contrasting AM retrieval with semantic memory (SM) retrieval. During scanning, participants were cued by verbal prompts to retrieve previously selected recent AMs or to verify semantic properties of words. As predicted, both groups showed AM retrieval-related increased activation in regions implicated in prior studies, including bilateral hippocampus, and prefrontal, posterior cingulate, and parietal cortices. Adults showed greater activation in the hippocampal/parahippocampal region as well as prefrontal and parietal cortex, relative to children; age-related differences were most prominent in the first 8?sec versus the second 8?sec of AM retrieval and when AM retrieval was contrasted with semantic retrieval. This study is the first to characterise similarities and differences during AM retrieval in children and adults using fMRI.