Right amygdalar and temporofrontal activation during autobiographic, but not during fictitious memory retrieval

What distinguishes the recall of real-life experiences from that of self-created, fictitious emotionally laden information? Both kinds of information belong to the episodic memory system. Autobiographic memories constitute that part of the episodic memory system that is composed of significant life episodes, primarily of the distant past. Functional imaging was used to study the neural networks engaged in retrieving autobiographic and fictitious information of closely similar content. The principally activated brain regions overlapped considerably and constituted temporal and inferior prefrontal regions plus the cerebellum. Selective activations of the right amygdala and the right ventral prefrontal cortex (at the level of the uncinate fascicle interconnnecting prefrontal and temporopolar areas) were found when subtracting fictitious from autobiographic retrieval. Furthermore, distinct foci in the left temporal lobe were engaged. These data demonstrate that autobiographic memory retrieval uses (at least in non-brain damaged individuals) a network of right hemispheric ventral prefrontal and temporopolar regions and left hemispheric lateral temporal regions. It is concluded that it is the experiential character, its special emotional infiltration and its arousal which distinguishes memory of real-life from that of fictitious episodes. Consequently, our results point to the engagement of a bi-hemispheric network in which the right temporo-prefrontal hemisphere is likely to be responsible for the affective/arousal side of information retrieval and the left-hemispheric temporal gyrus for its engram-like representation. Portions of the neural activation found during retrieval might, however, reflect re-encoding processes as well.     

Distinguishing the neural correlates of episodic memory encoding and semantic memory retrieval

Episodic memory and semantic memory interact very closely. In particular, episodic memory encoding (EE) tends to elicit semantic memory retrieval (SR), and vice versa. Thus, similar activations for EE and SR in functional neuroimaging studies may reflect shared memory processes, or they may reflect the fact that EE and SR are usually confounded. To address this issue, we used a factorial functional magnetic resonance imaging approach to disentangle the neural correlates of EE and SR. Within the left temporal lobe, the hippocampus was associated with successful EE, whereas a posterior lateral region was associated with successful SR. Within the left inferior prefrontal cortex, a posterior region was involved in SR, a mid region was involved in both SR and EE, and an anterior region was involved in EE, but only when SR was also high. Thus, the neural correlates of EE and SR are dissociable but interact in specific brain regions.     

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.     

PET studies of encoding and retrieval: The HERA model

We review positron emission tomography (PET) studies whose results converge on the hemispheric encoding/retrieval asymmetry (HERA) model of the involvement of prefrontal cortical regions in the processes of human memory. The model holds that the left prefrontal cortex is differentially more involved in retrieval of information from semantic memory, and in simultaneously encoding novel aspects of the retrieved information into episodic memory, than is the right prefrontal cortex. The right prefrontal cortex, on the other hand, is differentially more involved in episodic memory retrieval than is the left prefrontal cortex. This general pattern holds for different kinds of information (e.g., verbal materials, pictures, faces) and a variety of conditions of encoding and retrieval.     

The neural regions sustaining episodic encoding and recognition of objects

In this functional MRI experiment, encoding of objects was associated with activation in left ventrolateral prefrontal/insular and right dorsolateral prefrontal and fusiform regions as well as in the left putamen. By contrast, correct recognition of previously learned objects (R judgments) produced activation in left superior frontal, bilateral inferior frontal, and right cerebellar regions, whereas correct rejection of distractor objects (N judgments) was associated with activation in bilateral prefrontal and anterior cingulate cortices, in right parietal and cerebellar regions, in the left putamen, and in the right caudate nucleus. The R minus N comparison showed activation in the left lateral prefrontal cortex and in bilateral cingulate cortices and precunei, while the N minus R comparison did not reveal any positive signal change. These results support the view that similar regions of the frontal lobe are involved in episodic encoding and retrieval processes, and that the successful episodic retrieval of newly learned objects is mainly based on a frontoparietal network.     

Mental time travel into the past and the future in healthy aged adults: an fMRI study

Remembering the past and envisioning the future rely on episodic memory which enables mental time travel. Studies in young adults indicate that past and future thinking share common cognitive and neural underpinnings. No imaging data is yet available in healthy aged subjects. Using fMRI, we scanned older subjects while they remembered personal events (PP: last 12 months) or envisioned future plans (FP: next 12 months). Behaviorally, both time-periods were comparable in terms of visual search strategy, emotion, frequency of rehearsal and recency of the last evocation. However, PP were more episodic, engaged a higher state of autonoetic consciousness and mental visual images were clearer and more numerous than FP. Neuroimaging results revealed a common network of activation (posterior cingulate cortex, precuneus, prefrontal cortex, hippocampus) reflecting the use of similar cognitive processes. Furthermore, the episodic nature of PP depended on hippocampal and visuo-spatial activations (occipital and angular gyri), while, for FP, it depended on the inferior frontal and lateral temporal gyri, involved in semantic memory retrieval. The common neural network and behavior suggests that healthy aged subjects thought about their future prospects in the past. The contribution of retrospective thinking into the future that engages the same network as the one recruited when remembering the past is discussed. Within this network, differential recruitment of specific areas highlights the episodic distinction between past and future mental time travel.     

Mapping Cognition to the Brain Through Neural Interactions

Brain imaging methods, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), provide a unique opportunity to study the neurobiology of human memory. As these methods can measure most of the brain, it is possible to examine the operations of large-scale neural systems and their relation to cognition. Two neuroimaging studies, one concerning working memory and the other episodic memory retrieval, serve as examples of application of two analytic methods that are optimised for the quantification of neural systems, structural equation modelling, and partial least squares. Structural equation modelling was used to explore shifting prefrontal and limbic interactions from the right to the left hemisphere in a delayed match-to-sample task for faces. A feature of the functional network for short delays was strong right hemisphere interactions between hippocampus, inferior prefrontal, and anterior cingulate cortices. At longer delays, these same three areas were strongly linked, but in the left hemisphere, which was interpreted as reflecting change in task strategy from perceptual to elaborate encoding with increasing delay. The primary manipulation in the memory retrieval study was different levels of retrieval success. The partial least squares method was used to determine whether the image-wide pattern of covariances of Brodmann areas 10 and 45/47 in right prefrontal cortex (RPFC) and the left hippocampus (LGH) could be mapped on to retrieval levels. Area 10 and LGH showed an opposite pattern of functional connectivity with a large expanse of bilateral limbic cortices that was equivalent for all levels of retrieval as well as the baseline task. However, only during high retrieval was area 45/47 included in this pattern. The results suggest that activity in portions of the RPFC can reflect either memory retrieval mode or retrieval success depending on other brain regions to which it is functionally linked, and imply that regional activity must be evaluated within the neural context in which it occurs. The general hypothesis that learning and memory are emergent properties of large-scale neural network interactions is discussed, emphasising that a region can play a different role across many functions and that role is governed by its interactions with anatomically related regions.     

Mapping cognition to the brain through neural interactions

Brain imaging methods, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), provide a unique opportunity to study the neurobiology of human memory. As these methods can measure most of the brain, it is possible to examine the operations of large-scale neural systems and their relation to cognition. Two neuroimaging studies, one concerning working memory and the other episodic memory retrieval, serve as examples of application of two analytic methods that are optimised for the quantification of neural systems, structural equation modelling, and partial least squares. Structural equation modelling was used to explore shifting prefrontal and limbic interactions from the right to the left hemisphere in a delayed match-to-sample task for faces. A feature of the functional network for short delays was strong right hemisphere interactions between hippocampus, inferior prefrontal, and anterior cingulate cortices. At longer delays, these same three areas were strongly linked, but in the left hemisphere, which was interpreted as reflecting change in task strategy from perceptual to elaborate encoding with increasing delay. The primary manipulation in the memory retrieval study was different levels of retrieval success. The partial least squares method was used to determine whether the image-wide pattern of covariances of Brodmann areas 10 and 45/47 in right prefrontal cortex (RPFC) and the left hippocampus (LGH) could be mapped on to retrieval levels. Area 10 and LGH showed an opposite pattern of functional connectivity with a large expanse of bilateral limbic cortices that was equivalent for all levels of retrieval as well as the baseline task. However, only during high retrieval was area 45/47 included in this pattern. The results suggest that activity in portions of the RPFC can reflect either memory retrieval mode or retrieval success depending on other brain regions to which it is functionally linked, and imply that regional activity must be evaluated within the neural context in which it occurs. The general hypothesis that learning and memory are emergent properties of large-scale neural network interactions is discussed, emphasising that a region can play a different role across many functions and that role is governed by its interactions with anatomically related regions.     

In Search of the Self: A Positron Emission Tomography Study

Abstract—Previous work using positron emission tomography (PET) has shown that memory encoding processes are associated with preferential activation of left frontal regions of the brain, whereas retrieval processes are associated predominantly with right frontal activations. One possible reason for the asymmetry is that episodic retrieval necessarily involves reference to the self, and the self-concept may be represented (at least partially) in right frontal regions. Accordingly, the present study investigated the possibility that encoding of self-related material might also activate right frontal areas. Eight right-handed volunteers judged trait adjectives under four separate PET scan conditions: (a) relevance to self, (b) relevance to a well-known public figure, (c) social desirability, and (d) number of syllables. The results showed that self-related encoding yielded left frontal activations similar to those associated with other types of semantic encoding, but also specific activations in the right frontal lobe. It is concluded that the concept of self involves both general schematic structures and further specific components involved in episodic memory retrieval.     

相继记忆模式：展现情节记忆形成脑机制的窗口

相继记忆模式在记忆形成的脑认知成像研究领域应用广泛,已成为研究者探究大脑形成记忆时活动的主要窗口。该文在介绍相继记忆模式及记忆形成过程的基础上,分析影响相继记忆效应大小和时空分布的因素,最后讨论内侧颞叶及前额叶神经网络中相关脑区如何分工、协同支持情节记忆形成。情节记忆多维度特性导致该神经网络中有关区域表现出不同形式的相继记忆效应,因此,该文提出有效分离这些脑区在记忆形成中如何分工及交互协同关系进行更为重要     

Adult age differences in visual word identification: functional neuroanatomy by positron emission tomography

Adult age differences in the neural systems mediating semantic (context-independent) memory were investigated using positron emission tomography (PET). Younger (20-29 years) and older (62-70 years) participants performed lexical decision (word/nonword discrimination) and nonsemantic (simple visual search) baseline tasks during PET scanning. Within the lexical decision task, display duration and presentation rate were varied across scans. The behavioral data suggested that although an age-related slowing was evident in visual feature and response processing, the retrieval of semantic/lexical information was similar for younger and older adults. For both age groups, lexical-related activation occurred in inferior prefrontal and occipitotemporal regions of the left hemisphere. Differential activation, as a function of age group, was observed in the left occipitotemporal pathway as a result of older adults' maintaining higher levels of neural activity in striate cortex (during visual search) and in inferior temporal cortex (during lexical decision). The prefrontal activation was similar for the two age groups. Thus, although this form of semantic memory retrieval does not undergo significant age-related decline, an age-related change in the associated pattern of neural activation is evident. These findings differ from previous neuroimaging studies of episodic (context-dependent) memory retrieval, which have suggested that age-related compensatory mechanisms are expressed primarily by greater activation of prefrontal regions for older adults than for younger adults.     

rTMS for PTSD: induced merciful oblivion or elimination of abnormal hypermnesia?

Neuroimaging studies and experimental data suggest that symptoms of posttraumatic stress disorder (PTSD) are associated with dysfunctions of neural circuits linking prefrontal cortex and the limbic system that have a role in autobiographic episodic memory. High-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral prefrontal cortex (DLPFC) has been suggested to be beneficial to patients with PTSD, transiently alleviating re-experiencing as well as avoidance reactions and associated anxiety symptoms. In healthy humans, converging evidence suggests that rTMS of the right DLPFC interferes with episodic memory retrieval. Hence, we hypothesize that daily applications of rTMS in PTSD patients may reduce access to the set of autobiographical stored events, that, if re-experienced, may cause the overt PTSD symptoms.     

Learning related modulation of functional retrieval networks in man

The medial temporal lobe has been implicated in studies of episodic memory tasks involving spatio-temporal context and object-location conjunctions. We have previously demonstrated that an increased level of practice in a free-recall task parallels a decrease in the functional activity of several brain regions, including the medial temporal lobe, the prefrontal, the anterior cingulate, the anterior insular, and the posterior parietal cortices, that in concert demonstrate a move from elaborate controlled processing towards a higher degree of automaticity. Here we report data from two experiments that extend these initial observations. We used a similar experimental approach but probed for effects of retrieval paradigms and stimulus material. In the first experiment we investigated practice related changes during recognition of object-location conjunctions and in the second during free-recall of pseudo-words. Learning in a neural network is a dynamic consequence of information processing and network plasticity. The present and previous PET results indicate that practice can induce a learning related functional restructuring of information processing. Different adaptive processes likely subserve the functional re-organisation observed. These may in part be related to different demands for attentional and working memory processing. It appears that the role(s) of the prefrontal cortex and the medial temporal lobe in memory retrieval are complex, perhaps reflecting several different interacting processes or cognitive components. We suggest that an integrative interactive perspective on the role of the prefrontal and medial temporal lobe is necessary for an understanding of the processing significance of these regions in learning and memory. It appears necessary to develop elaborated and explicit computational models for prefrontal and medial temporal functions in order to derive detailed empirical predictions, and in combination with an efficient use and development of functional neuroimaging approaches, to further the understanding of the processing significance of these regions in memory.     

Brain activation during episodic memory retrieval: sex differences

Behavioral studies have shown a tendency for women to outperform men on episodic memory tasks. Here, data from a series of positron emission tomography (PET) studies were analyzed to examine sex differences in brain activity associated with episodic memory retrieval (yes/no recognition). A total of 17 women and 17 men were included in the analyses. The strongest effect of the design was a retrieval-related increase in activity, involving right prefrontal and anterior cingulate regions, that was common to women and men. In addition, a significant task-by-sex interaction effect was observed which involved a distributed set of brain regions, including several frontal areas. These results suggest that while the neural correlate of episodic memory retrieval is largely the same for men and women, some differences do exist. Possible explanations for the observed differences are discussed, and it is concluded that biological and experiential factors jointly contribute to sex differences in brain activity.     

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.     

对人类不良记忆的修饰：来自记忆再巩固的证据

已经巩固的长时记忆被再次提取后, 进入一个记忆的不稳定期, 在此过程中, 记忆可被更新、强化、削弱甚至抹除, 这个过程称为再巩固。人类不良记忆再巩固研究揭示记忆激活后口服普萘洛尔(propranolol)或进行消退训练可削弱或抹除不良情绪记忆, 此过程中涉及杏仁核、海马、前额叶皮层等脑区的参与及其构成的神经环路的调控。当前临床上利用再巩固原理可通过药物治疗、行为干预或无创脑部刺激的方法改变不良记忆。然而, 由于其形成过程复杂并受多种因素影响, 未来研究应尽可能模拟临床中人类不良记忆形成的复杂环境, 深入探讨再巩固“边界问题”, 推动实验室研究向临床应用的转化。     

Prefrontal and hippocampal contributions to visual associative recognition: interactions between cognitive control and episodic retrieval

The ability to recover episodic associations is thought to depend on medial-temporal lobe mnemonic mechanisms and frontal lobe cognitive control processes. The present study examined the neural circuitry underlying non-verbal associative retrieval, and considered the consequences of successful retrieval on cognitive control demands. Event-related fMRI data were acquired while subjects retrieved strongly or weakly associated pairs of novel visual patterns in a two-alternative forced choice associative recognition paradigm. Behaviorally, successful retrieval of strongly associated relative to weakly associated pairs was more likely to be accompanied by conscious recollection of the pair's prior co-occurrence. At the neural level, right ventrolateral prefrontal cortex (VLPFC) and hippocampus were more active during successful retrieval of Strong than of Weak associations, consistent with a role in visual associative recollection. By contrast, Weak trials elicited greater activation in right anterior cingulate cortex (ACC), which may detect conflict between the similarly familiar target and foil stimuli in the absence of recollection. Consistent with this interpretation, stronger ACC activity was associated with weaker hippocampal and stronger right dorsolateral PFC (DLPFC) responses. Thus, recollection of relevant visual associations (hippocampus and VLPFC) results in lower levels of mnemonic conflict (ACC) and decreased familiarity-based monitoring demands (DLPFC). These findings highlight the interplay between cognitive control and episodic retrieval.     

Cognitive neuroscience of episodic memory encoding

This paper presents a cognitive neuroscientific perspective on how human episodic memories are formed. Convergent evidence from multiple brain imaging studies using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) suggests a role for frontal cortex in episodic memory encoding. Activity levels within frontal cortex can predict episodic memory encoding across a wide range of behavioral manipulations known to influence memory performance, such as those present during levels of processing and divided attention manipulations. Activity levels within specific frontal and medial temporal regions can even predict, on an item by item basis, whether an episodic memory is likely to form. Furthermore, separate frontal regions appear to participate in supplying code-specific information, including distinct regions which process semantic attributes of verbal information as well as right-lateralized regions which process nonverbal information. We hypothesize that activity within these multiple frontal regions provides a functional influence (input) to medical temporal regions that bind the information together into a lasting episodic memory trace.     

How does a child solve 7 + 8? Decoding brain activity patterns associated with counting and retrieval strategies

Cognitive development and learning are characterized by diminished reliance on effortful procedures and increased use of memory-based problem solving. Here we identify the neural correlates of this strategy shift in 7-9-year-old children at an important developmental period for arithmetic skill acquisition. Univariate and multivariate approaches were used to contrast brain responses between two groups of children who relied primarily on either retrieval or procedural counting strategies. Children who used retrieval strategies showed greater responses in the left ventrolateral prefrontal cortex; notably, this was the only brain region which showed univariate differences in signal intensity between the two groups. In contrast, multivariate analysis revealed distinct multivoxel activity patterns in bilateral hippocampus, posterior parietal cortex and left ventrolateral prefrontal cortex regions between the two groups. These results demonstrate that retrieval and counting strategies during early learning are characterized by distinct patterns of activity in a distributed network of brain regions involved in arithmetic problem solving and controlled retrieval of arithmetic facts. Our findings suggest that the reorganization and refinement of neural activity patterns in multiple brain regions plays a dominant role in the transition to memory-based arithmetic problem solving. Our findings further demonstrate how multivariate approaches can provide novel insights into fine-scale developmental changes in the brain. More generally, our study illustrates how brain imaging and developmental research can be integrated to investigate fundamental aspects of neurocognitive development.     

Episodic retrieval and the cortical binding of relational activity

Retrieval of episodic memories depends on the successful “re-collection” of event features, such as the time, place, people, thoughts, and feelings associated with a past experience.In neuroimaging studies, ventral regions of the posterior parietal cortex (vPPC) are particularly active when episodic memories are successfully retrieved. A review of the neural correlates of episodic retrieval is presented along with a new theory, cortical binding of relational activity (CoBRA). According to CoBRA, the vPPC acts as a convergence zone that binds episodic features stored in disparate neocortical regions. This process works in conjunction with other known mechanisms, such as those associated with the prefrontal cortex and medial temporal lobe.