The neural basis of episodic memory: evidence from functional neuroimaging

We review some of our recent research using functional neuroimaging to investigate neural activity supporting the encoding and retrieval of episodic memories, that is, memories for unique events. Findings from studies of encoding indicate that, at the cortical level, the regions responsible for the effective encoding of a stimulus event as an episodic memory include some of the regions that are also engaged to process the event 'online'. Thus, it appears that there is no single cortical site or circuit responsible for episodic encoding. The results of retrieval studies indicate that successful recollection of episodic information is associated with activation of lateral parietal cortex, along with more variable patterns of activity in dorsolateral and anterior prefrontal cortex. Whereas parietal regions may play a part in the representation of retrieved information, prefrontal areas appear to support processes that act on the products of retrieval to align behaviour with the demands of the retrieval task.     

The Cognitive Control of Memory: Age Differences in the Neural Correlates of Successful Remembering and Intentional Forgetting

Successful memory encoding depends on the ability to intentionally encode relevant information (via differential encoding) and intentionally forget that which is irrelevant (via inhibition). Both cognitive processes have been shown to decline in aging and are theorized to underlie age-related deficits in the cognitive control of memory. The current study uses the Directed Forgetting paradigm in conjunction with fMRI to investigate age-related differences in both cognitive processes, with the specific aim of elucidating neural evidence supporting these theorized deficits. Results indicate relatively preserved differential encoding, with age differences consistent with previous models of age-related compensation (i.e., increased frontal and bilateral recruitment). Older adults did display noticeable differences in the recruitment of brain regions related to intentional forgetting, specifically exhibiting reduced activity in the right superior prefrontal cortex, a region shown to be critical to inhibitory processing. However, older adults exhibited increased reliance on processing in right inferior parietal lobe associated with successful forgetting. Activity in this region was negatively correlated with activity in the medial temporal lobe, suggesting a shift in the locus of inhibition compared to the frontally mediated inhibition observed in younger adults. Finally, while previous studies found intentional and incidental forgetting to be dissociable in younger adults, this differentiation appears to be reduced in older adults. The current results are the first to provide neural evidence for an age-related reduction in processes that support intentional forgetting.     

Retrieval Intention Modulates the Effects of Directed Forgetting Instructions on Recollection

The neurocognitive basis of memory retrieval is often examined by investigating brain potential old/new effects, which are differences in brain activity between successfully remembered repeated stimuli and correctly rejected new stimuli in a recognition test. In this study, we combined analyses of old/new effects for words with an item-method directed-forgetting manipulation in order to isolate differences between the retrieval processes elicited by words that participants were initially instructed to commit to memory and those that participants were initially instructed to forget. We compared old/new effects elicited by to-be-forgotten (TBF) words with those elicited by to-be-remembered (TBR) words in both an explicit-memory test (a recognition test) and an implicit-memory test (a lexical-decision test). Behavioral results showed clear directed forgetting effects in the recognition test, but not in the lexical decision test. Mirroring the behavioral findings, analyses of brain potentials showed evidence of directed forgetting only in the recognition test. In this test, potentials from 450–650 ms (P600 old/new effects) were more positive for TBR relative to TBF words. By contrast, P600 effects evident during the lexical-decision test did not differ in magnitude between TBR and TBF items. When taken in the context of prior studies that have linked similar parietal old/new effects to the recollection of episodic information, these data suggest that directed-forgetting effects manifest primarily in greater episodic retrieval by TBR than TBF items, and that retrieval intention may be important for these directed-forgetting effects to occur.     

Directed Forgetting of Negative Self-Referential Information Is Difficult: An fMRI Study

A large body of evidence suggested that both emotion and self-referential processing can enhance memory. However, it remains unclear how these two factors influence directed forgetting. This study speculates that directed forgetting of negative self-referential memory is more difficult than forgetting of other-referential memory. To verify this speculation, we combined the directed forgetting paradigm with the self-reference task. The behavioral result suggested that although both self-referential and other-referential information can be directly forgotten, less self-referential information can be forgotten than other-referential information. At the neural level, the forget instruction strongly activated the frontal cortex, suggesting that directed forgetting is not memory decay but an active process. In addition, compared with the negative other-referential information, forgetting of the negative self-referential information were associated with a more widespread activation, including the orbital frontal gyrus (BA47), the inferior frontal gyrus (BA45, BA44), and the middle frontal gyrus. Our results suggest that forgetting of the self-referential information seems to be a more demanding and difficult process.     

When more means less: neural activity related to unsuccessful memory encoding

The neural correlates of memory encoding have been studied by contrasting neural activity elicited by items at the time of learning according to whether they were later remembered or forgotten [1]. Previous studies have focused on regions where neural activity is greater for subsequently remembered items [2-8]. Here, we describe regions where activity is greater for subsequently forgotten items. In two experiments that employed the same incidental learning task, activity in an overlapping set of cortical regions (posterior cingulate, inferior and medial parietal, and dorsolateral prefrontal) was associated with failure on a subsequent memory test.     

Dissociating memory retrieval processes using fMRI: evidence that priming does not support recognition memory

We employed event-related fMRI to constrain cognitive accounts of memory retrieval. Studies of explicit retrieval reveal that lateral and medial parietal, dorsal middle frontal gyrus, and anterior prefrontal cortex respond more for studied than new words, reflecting a correlate of "retrieval success." Studies of implicit memory suggest left temporal cortex, ventral and dorsal inferior frontal gyrus respond less for studied than new words, reflecting a correlate of "conceptual priming." In the present study, responses for old and new items were compared during performance on explicit recognition (old/new judgement) and semantic (abstract/concrete judgement) tasks. Regions associated with priming were only modulated during the semantic task, whereas regions associated with retrieval success were modulated during both tasks. These findings constrain functional-anatomic accounts of the networks, suggesting that processes associated with priming do not support explicit recognition judgments.     

Identifying distinct components in the cerebral treatment of visual sexual information through functional neuroimaging

For now several years, the growing developement of neuroimaging techniques such as Positron Emission Tomography (PET) or functional Magnetic Resonance Imaging (fMRI) allowed a better understanding of neural processes involved in human emotions and goal-directed behaviors. In particular, several studies are now available on the neural correlates of male sexual arousal. A neurobehavioral model of neural processes involved in sexual arousal has been proposed (Redouté et al., 2000) comprising: i) a cognitive component; ii) an emotional component; iii) a motivational component and iv) an autonomic component. Among other regions, several cerebral areas have been found to be linked to: 1) the cognitive component which comprises: i) the orbitofrontal cortex involved in attentional processes directed toward the target and the superior parietal lobules; ii) the inferior parietal lobules involved in motor imagery processes; 2) the motivational component which involves the caudal part of the anterior cingulate cortex, related to motor preparation processes; 3) the autonomic component: concurrent measures of cerebral activations by functional neuroimaging and of erectile response by penile plethysmography allow the demonstration of the involvement of the hypothalamus, the insula, and the rostral part of the anterior cingulate cortex in this component.     

Dissociable Temporo-Parietal Memory Networks Revealed by Functional Connectivity during Episodic Retrieval

Episodic memory retrieval most often recruits multiple separate processes that are thought to involve different temporal regions. Previous studies suggest dissociable regions in the left lateral parietal cortex that are associated with the retrieval processes. Moreover, studies using resting-state functional connectivity (RSFC) have provided evidence for the temporo-parietal memory networks that may support the retrieval processes. In this functional MRI study, we tested functional significance of the memory networks by examining functional connectivity of brain activity during episodic retrieval in the temporal and parietal regions of the memory networks. Recency judgments, judgments of the temporal order of past events, can be achieved by at least two retrieval processes, relational and item-based. Neuroimaging results revealed several temporal and parietal activations associated with relational/item-based recency judgments. Significant RSFC was observed between one parahippocampal region and one left lateral parietal region associated with relational recency judgments, and between four lateral temporal regions and another left lateral parietal region associated with item-based recency judgments. Functional connectivity during task was found to be significant between the parahippocampal region and the parietal region in the RSFC network associated with relational recency judgments. However, out of the four tempo-parietal RSFC networks associated with item-based recency judgments, only one of them (between the left posterior lateral temporal region and the left lateral parietal region) showed significant functional connectivity during task. These results highlight the contrasting roles of the parahippocampal and the lateral temporal regions in recency judgments, and suggest that only a part of the tempo-parietal RSFC networks are recruited to support particular retrieval processes.     

Hippocampal involvement in human topographical memory: evidence from functional imaging.

Functional brain imaging in humans is beginning to reveal a network of brain regions that subserve topographical learning: the medial parietal lobe, the posterior cingulate gyrus, occipitotemporal areas, the parahippocampal gyrus and the right hippocampus. These findings illuminate the patient lesion literature where all of these brain regions have been implicated at one time or another in cases of topographical disorientation. Once topographical information is acquired, the neuroanatomy that supports its use from either episodic or semantic memory is similar to that activated during encoding. The specific contributions of extrahippocampal regions within the topographical memory system are being revealed, such as the role of the right parahippocampal gyrus in object-in-place encoding. The right hippocampus is clearly involved in processing spatial layouts over long as well as short time-courses, and participates in both the encoding and the retrieval of topographical memory. The ventromedial orbitofrontal cortex is recruited when information in the topographical memory system is not sufficient to produce direct navigation to a goal place.     

Costs of acquiring and forgetting information affect spatial memory and its susceptibility to interference

Acquiring and storing information in memory is constrained by the limited capacity of attentional and short-term memory systems. Therefore, processes that prioritize information for storage in memory according to its survival value to the organism are likely to have evolved. Information incurring energy or time costs to acquire, or if forgotten, should be stored and retrieved more effectively than information that is less costly to acquire or forget. We manipulated the costs of acquiring and forgetting information in an eight-arm radial maze memory task for pigs, Sus scrofa, by placing ropes at the entrance to arms, which pigs had to walk over incurring an extra 2-3-s time cost for each arm entry. Each day each pig (N=16) made a sampling visit to the maze to find food in four arms, followed by a 10-min retention interval, and a recall visit in which visits to the four previously empty arms were reinforced. Baited arms were varied daily. Pigs were divided into four groups and exposed to ropes (costs) either during sampling only, recall only, both or neither. Exposure to costs during sampling visits decreased errors during recall visits. This was probably the result of enhanced attention to and encoding of information during sampling. When all groups were performing equally well, retroactive interference treatments revealed hidden differences between them. Groups experiencing costs during recall tests were least susceptible to interference effects, probably because of more considered use of retrieved information. Both memory encoding and retrieval processes may thus be modulated by even small costs of obtaining or forgetting information.     

Task and content modulate amygdala-hippocampal connectivity in emotional retrieval

The ability to remember emotional events is crucial for adapting to biologically and socially significant situations. Little is known, however, about the nature of the neural interactions supporting the integration of mnemonic and emotional information. Using fMRI and dynamic models of effective connectivity, we examined regional neural activity and specific interactions between brain regions during a contextual memory retrieval task. We independently manipulated emotional context and relevance of retrieved emotional information to task demands. We show that retrieval of emotionally valenced contextual information is associated with enhanced connectivity from hippocampus to amygdala, structures crucially involved with encoding of emotional events. When retrieval of emotional information is relevant to current behavior, amygdala-hippocampal connectivity increases bidirectionally, under modulatory influences from orbitofrontal cortex, a region implicated in representation of affective value and behavioral guidance. Our findings demonstrate that both memory content and behavioral context impact upon large scale neuronal dynamics underlying emotional retrieval.     

Parietal and hippocampal contribution to topokinetic and topographic memory.

This paper reviews the involvement of the parietal cortex and the hippocampus in three kinds of spatial memory tasks which all require a memory of a previously experienced movement in space. The first task compared, by means of positron emission tomography (PET) scan techniques, the production, in darkness, of self-paced saccades (SAC) with the reproduction, in darkness, of a previously learned sequence of saccades to visual targets (SEQ). The results show that a bilateral increase of activity was seen in the depth of the intraparietal sulcus and the medial superior parietal cortex (superior parietal gyrus and precuneus) together with the frontal sulcus but only in the SEQ task, which involved memory of the previously seen targets and possibly also motor memory. The second task is the vestibular memory contingent task, which requires that the subject makes, in darkness, a saccade to the remembered position of a visual target after a passively imposed whole-body rotation. Deficits in this task, which involves vestibular memory, were found predominantly in patients with focal vascular lesions in the parieto-insular (vestibular) cortex, the supplementary motor area-supplementary eye field area, and the prefrontal cortex. The third task requires mental navigation from the memory of a previously learned route in a real environment (the city of Orsay in France). A PET scan study has revealed that when subjects were asked to remember visual landmarks there was a bilateral activation of the middle hippocampal regions, left inferior temporal gyrus, left hippocampal regions, precentral gyrus and posterior cingulate gyrus. If the subjects were asked to remember the route, and their movements along this route, bilateral activation of the dorsolateral cortex, posterior hippocampal areas, posterior cingulate gyrus, supplementary motor areas, right middle hippocampal areas, left precuneus, middle occipital gyrus, fusiform gyrus and lateral premotor area was found. Subtraction between the two conditions reduced the activated areas to the left hippocampus, precuneus and insula. These data suggest that the hippocampus and parietal cortex are both involved in the dynamic aspects of spatial memory, for which the name ''topokinetic memory'' is proposed. These dynamic aspects could both overlap and be different from those involved in the cartographic and static aspects of ''topographic'' memory.     

Recurrent activity in higher order, modality non-specific brain regions: a Granger causality analysis of autobiographic memory retrieval

It has been proposed that the workings of the brain are mainly intrinsically generated recurrent neuronal activity, with sensory inputs as modifiers of such activity in both sensory and higher order modality non-specific regions. This is supported by the demonstration of recurrent neuronal activity in the visual system as a response to visual stimulation. In contrast recurrent activity has never been demonstrated before in higher order modality non-specific regions. Using magneto-encephalography and Granger causality analysis, we tested in a paralimbic network the hypothesis that stimulation may enhance causal recurrent interaction between higher-order, modality non-specific regions. The network includes anterior cingulate/medial prefrontal and posterior cingulate/medial parietal cortices together with pulvinar thalami, a network known to be effective in autobiographic memory retrieval and self-awareness. Autobiographic memory retrieval of previous personal judgments of visually presented words was used as stimuli. It is demonstrated that the prestimulus condition is characterized by causal, recurrent oscillations which are maximal in the lower gamma range. When retrieving previous judgments of visually presented adjectives, this activity is dramatically increased during the stimulus task as ascertained by Granger causality analysis. Our results confirm the hypothesis that stimulation may enhance causal interaction between higher order, modality non-specific brain regions, exemplified in a network of autobiographical memory retrieval.     

Grey and White Matter Correlates of Recent and Remote Autobiographical Memory Retrieval – Insights from the Dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer''s disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer''s disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events.     

fMRI reveals how pain modulates visual object processing in the ventral visual stream

It is well known that pain attracts attention and interferes with cognition. Given that the mechanisms behind this phenomenon are largely unknown, we used functional magnetic resonance imaging and presented visual objects with or without concomitant pain stimuli. To test for the specificity of pain, we compared this modulatory effect with a previously established modulatory effect of working memory on visual object processing. Our data showed a comparable behavioral effect of both types of modulation and identified the lateral occipital complex (LOC) as the site of modulation in the ventral visual stream, for both pain and working memory. However, the sources of these modulatory effects differed for the two processes. Whereas the source of modulation for working memory could be attributed to the parietal cortex, the modulatory effect of pain was observed in the rostral anterior cingulate cortex (rACC), an area ideally suited to link pain perception and attentional control.     

Monitoring the mind: the neurocognitive correlates of metamemory

Memory performance in everyday life is often far from perfect and therefore needs to be monitored and controlled by metamemory evaluations, such as judgments of learning (JOLs). JOLs support monitoring for goal-directed modification of learning. Behavioral studies suggested retrieval processes as providing a basis for JOLs. Previous functional imaging research on JOLs found a dissociation between processes underlying memory prediction, located in the medial prefrontal cortex (mPFC), and actual encoding success, located in the medial temporal lobe. However, JOL-specific neural correlates could not be identified unequivocally, since JOLs were given simultaneously with encoding. Here, we aimed to identify the neurocognitive basis of JOLs, i.e., the cognitive processes and neural correlates of JOL, separate from initial encoding. Using functional magnetic resonance imaging (fMRI), we implemented a face-name paired associative design. In general, we found that actual memory success was associated with increased brain activation of the hippocampi bilaterally, whereas predicted memory success was accompanied by increased activation in mPFC, orbital frontal and anterior cingulate cortices. Masking brain activation during predicted memory success with activation during retrieval success revealed BOLD increases of the mPFC. Our findings indicate that JOLs actually incorporate retrieval processes.     

Different Roles of COMT and HTR2A Genotypes in Working Memory Subprocesses

Working memory is linked to the functions of the frontal areas, in which neural activity is mediated by dopaminergic and serotonergic tones. However, there is no consensus regarding how the dopaminergic and serotonergic systems influence working memory subprocesses. The present study used an imaging genetics approach to examine the interaction between neurochemical functions and working memory performance. We focused on functional polymorphisms of the catechol-O-methyltransferase (COMT) Val¹⁵⁸Met and serotonin 2A receptor (HTR2A) -1438G/A genes, and devised a delayed recognition task to isolate the encoding, retention, and retrieval processes for visual information. The COMT genotypes affected recognition accuracy, whereas the HTR2A genotypes were associated with recognition response times. Activations specifically related to working memory were found in the right frontal and parietal areas, such as the middle frontal gyrus (MFG), inferior frontal gyrus (IFG), anterior cingulate cortex (ACC), and inferior parietal lobule (IPL). MFG and ACC/IPL activations were sensitive to differences between the COMT genotypes and between the HTR2A genotypes, respectively. Structural equation modeling demonstrated that stronger connectivity in the ACC-MFG and ACC-IFG networks is related to better task performance. The behavioral and fMRI results suggest that the dopaminergic and serotonergic systems play different roles in the working memory subprocesses and modulate closer cooperation between lateral and medial frontal activations.     

Mirroring intentional forgetting in a shared-goal learning situation

Background

Intentional forgetting refers to the surprising phenomenon that we can forget previously successfully encoded memories if we are instructed to do so. Here, we show that participants cannot only intentionally forget episodic memories but they can also mirror the “forgetting performance” of an observed model.

Methodology/Principal Findings

In four experiments a participant observed a model who took part in a memory experiment. In Experiment 1 and 2 observers saw a movie about the experiment, whereas in Experiment 3 and 4 the observers and the models took part together in a real laboratory experiment. The observed memory experiment was a directed forgetting experiment where the models learned two lists of items and were instructed either to forget or to remember the first list. In Experiment 1 and 3 observers were instructed to simply observe the experiment (“simple observation” instruction). In Experiment 2 and 4, observers received instructions aimed to induce the same learning goal for the observers and the models (“observation with goal-sharing” instruction). A directed forgetting effect (the reliably lower recall of to-be-forgotten items) emerged only when models received the “observation with goal-sharing” instruction (P<.001 in Experiment 2, and P<.05 in Experiment 4), and it was absent when observers received the “simple observation” instruction (P>.1 in Experiment 1 and 3).

Conclusion

If people observe another person with the same intention to learn, and see that this person is instructed to forget previously studied information, then they will produce the same intentional forgetting effect as the person they observed. This seems to be a an important aspect of human learning: if we can understand the goal of an observed person and this is in line with our behavioural goals then our learning performance will mirror the learning performance of the model.     

Differential roles for parietal and occipital cortices in visual working memory

Visual working memory (VWM) is known as a highly capacity-limited cognitive system that can hold 3-4 items. Recent studies have demonstrated that activity in the intraparietal sulcus (IPS) and occipital cortices correlates with the number of representations held in VWM. However, differences among those regions are poorly understood, particularly when task-irrelevant items are to be ignored. The present fMRI-based study investigated whether memory load-sensitive regions such as the IPS and occipital cortices respond differently to task-relevant information. Using a change detection task in which participants are required to remember pre-specified targets, here we show that while the IPS exhibited comparable responses to both targets and distractors, the dorsal occipital cortex manifested significantly weaker responses to an array containing distractors than to an array containing only targets, despite that the number of objects presented was the same for the two arrays. These results suggest that parietal and occipital cortices engage differently in distractor processing and that the dorsal occipital, rather than parietal, activity appears to reflect output of stimulus filtering and selection based on behavioral relevance.     

Common prefrontal regions coactivate with dissociable posterior regions during controlled semantic and phonological tasks

One of the most ubiquitous findings in functional neuroimaging research is activation of left inferior prefrontal cortex (LIPC) during tasks requiring controlled semantic retrieval. Here we show that LIPC participates in the controlled retrieval of nonsemantic representations as well as semantic representations. Results also demonstrate that LIPC coactivates with dissociable posterior regions depending on the information retrieved: activating with left temporal cortex during the controlled retrieval of semantics and with left posterior frontal and parietal cortex during the controlled retrieval of phonology. Correlation of performance to LIPC activation suggests a processing role associated with mapping relatively ambiguous stimulus-to-representation relationships during both semantic and phonological tasks. These findings suggest that LIPC participates in controlled processing across multiple information domains collaborating with dissociable posterior regions depending upon the kind of information retrieved.