The Neuroimaging of Long-term Memory Encoding Processes

There needs to be more crosstalk between the lesion and functional neuroimaging memory literatures. This is illustrated by a discussion of episode and fact encoding. The lesion literature suggests several hypotheses about which brain regions underlie the storage of episode and fact information, which can be explored by functional neuroimaging. These hypotheses have been underexplored because neuroimaging studies of encoding have been insufficiently hypothesis-driven and have not controlled encoding-related processes sufficiently well to allow clear interpretations of results to be made. Nevertheless, there is good evidence that certain kinds of associative encoding and/or consolidation are sufficient to activate the medial temporal lobes, and preliminary evidence that some kinds of associative priming may reduce activation of this region. It remains to be proved that attentional orienting to certain kinds of novel information activates the medial temporal lobes. Evidence is growing that the HERA model, developed from neuroimaging rather than lesion data, requires modification and that frontal cortex encoding activations are probably caused by executive processes that are important in effortful memory processing. Neuroimaging studies allow the detection of encoding-related activations in previously unexpected brain regions (e.g. parietal lobes) and, in turn, these findings can be explored with lesion studies.     

Storage of verbal associations is sufficient to activate the left medial temporal lobe

Neuroimaging studies have shown that memory encoding activates the medial temporal lobe (MTL). Many believe that these activations are related to novelty but it remains unproven which is critical - novelty detection or the rich associative encoding it triggers. We examined MTL activation during verbal associative encoding using functional magnetic resonance imaging. First, associative encoding activated left posterior MTL more than single word encoding even though novelty detection was matched, indicating not only that associative encoding activates the MTL particularly strongly, but also that activation does not require novelty detection. Moreover, it remains to be convincingly shown that novelty detection alone does produce such activation. Second, repetitive associative encoding produced less MTL activation than initial associative encoding, indicating that priming of associative information reduces MTL activation. Third, re-encoding familiar associations in a well-established way had a minimal effect on both memory and MTL activation, indicating that MTL activation reflects storage of associations, not merely their initial representation.     

Storage of verbal associations is sufficient to activate the left medial temporal lobe

Neuroimaging studies have shown that memory encoding activates the medial temporal lobe (MTL). Many believe that these activations are related to novelty but it remains unproven which is critical - novelty detection or the rich associative encoding it triggers. We examined MTL activation during verbal associative encoding using functional magnetic resonance imaging. First, associative encoding activated left posterior MTL more than single word encoding even though novelty detection was matched, indicating not only that associative encoding activates the MTL particularly strongly, but also that activation does not require novelty detection. Moreover, it remains to be convincingly shown that novelty detection alone does produce such activation. Second, repetitive associative encoding produced less MTL activation than initial associative encoding, indicating that priming of associative information reduces MTL activation. Third, re-encoding familiar associations in a well-established way had a minimal effect on both memory and MTL activation, indicating that MTL activation reflects storage of associations, not merely their initial representation.     

Neural correlates of successful and unsuccessful verbal memory encoding

Recent neuroimaging studies suggest that episodic memory encoding involves a network of neocortical structures which may act interdependently with medial temporal lobe (mTL) structures to promote the formation of durable memories, and that activation in certain structures is modulated according to task performance. Functional magnetic resonance imaging (fMRI) was used to determine the neural structures recruited during a verbal episodic encoding task and to examine the relationship between activation during encoding and subsequent recognition memory performance across subjects. Our results show performance-correlated activation during encoding both in neocortical and medial temporal structures. Neocortical activations associated with later successful and unsuccessful recognition memory were found to differ not only in magnitude, but also in hemispheric laterality. These performance-related hemispheric effects, which have not been previously reported, may correspond to between-subject differences in encoding strategy.     

Associative memory and the medial temporal lobes

Associative recognition and recall depend on structures in the medial temporal lobes (MTLs). There is disagreement about whether associative memory is functionally heterogeneous, whether it is functionally distinct from intra-item associative memory and how the MTLs contribute to this kind of memory. Despite an increase in research on associative memory, work has lacked a theoretical framework to guide design and interpretation of studies. One view provides a useful framework by postulating that associative memories differ in the degree to which their informational components converge in MTL structures that create familiarity-supporting or recollection-supporting memory representations. Using this framework, we consider psychological, lesion and functional imaging evidence, highlighting how informational convergence in the brain underlies the associative nature of both memory and perception.     

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.     

Neural correlates underlying true and false associative memories

Despite the fact that associative memory studies produce a large number of false memories, neuroimaging analyses utilizing this paradigm typically focus only on neural activity mediating successful retrieval. The current study sought to expand on this prior research by examining the neural basis of both true and false associative memories. Though associative false memories are substantially different than those found in semantic or perceptual false memory paradigms, results suggest that associative false memories are mediated by similar neural mechanisms. Specifically, we found increased frontal activity that likely represents enhanced monitoring and evaluation compared to that needed for true memories and correct rejections. Results also indicated that true, and not false associative memories, are mediated by neural activity in the MTL, specifically the hippocampus. Finally, while activity in early visual cortex distinguished true from false memories, a lack of neural differences between hits and correct rejections failed to support previous findings suggesting that activity in early visual cortex represents sensory reactivation of encoding-related processing.     

Lateral and medial prefrontal contributions to emotion generation by semantic elaboration during episodic encoding

Memories for emotion-laden stimuli are remembered more accurately than those for neutral stimuli. Although this enhancement reflects stimulus-driven modulation of memory by emotions, functional neuroimaging evidence of the interacting mechanisms between emotions generated by intentional processes, such as semantic elaboration, and memory is scarce. The present fMRI study investigated how encoding-related activation is modulated by emotions generated during the process of semantic elaboration. During encoding with fMRI, healthy young adults viewed neutral (target) pictures either passively or with semantic elaboration. In semantic elaboration, participants imagined background stories related to the pictures. Encoding trials with semantic elaboration were subdivided into conditions in which participants imagined negative, positive, or neutral stories. One week later, memories for target pictures were tested. In behavioral results, memories for target pictures were significantly enhanced by semantic elaboration, compared to passive viewing, and the memory enhancement was more remarkable when negative or positive stories were imagined. fMRI results demonstrated that activations in the left inferior frontal gyrus and dorsal medial prefrontal cortex (dmPFC) were greater during the encoding of target pictures with semantic elaboration than those with passive viewing, and that these activations further increased during encoding with semantic elaboration of emotional stories than of neutral stories. Functional connectivity between the left inferior frontal gyrus and dmPFC/hippocampus during encoding significantly predicted retrieval accuracies of memories encoded with self-generated emotional stories. These findings suggest that networks including the left inferior frontal region, dmPFC, and hippocampus could contribute to the modulation of memories encoded with the emotion generation.     

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.     

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.     

The multiple neural networks of familiarity: A meta-analysis of functional imaging studies

Recent research has demonstrated the critical role of the feeling of familiarity in recognition memory. Various neuroimaging paradigms have been developed to identify the brain regions that sustain the processing of familiarity; however, there is still considerable controversy about the functional significance of each brain region implicated in familiarity-based retrieval. Here, we focused on the differences between paradigms that assess familiarity, with or without the encoding phase. We used the activation likelihood estimation (ALE) algorithm to conduct a whole-brain meta-analysis of neuroimaging studies that involved a familiarity task. Sixty-nine studies, performed in healthy subjects to determine the specific functions of the identified regions in familiarity processing, were finally selected. Distinct subanalyses were performed according to the experimental procedures used in the original studies. The ALE clusters that were highlighted revealed common activations for paradigms with and without encoding in the prefrontal cortex and in the parietal cortex. Additionally, supplementary activations related to specific familiarity (i.e., without the encoding phase) were observed in the limbic system (i.e., the amygdala, hippocampus, cingulate cortex, and insula) and in the associative sensory areas. The differences in the reported findings for different procedures are possibly due to differences in the concept of familiarity. To aid the exploration of the neural correlates of familiarity in future studies, the strengths and weaknesses of these experimental procedures are critically discussed.     

Lateralized spatial and object memory encoding in entorhinal and perirhinal cortices

The perirhinal and entorhinal cortices are critical components of the medial temporal lobe (MTL) declarative memory system. Study of their specific functions using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI), however, has suffered from severe magnetic susceptibility signal dropout resulting in poor temporal signal-to-noise (tSNR) and thus weak BOLD signal detectability. We have demonstrated that higher spatial resolution in the z-plane leads to improved BOLD fMRI signal quality in the anterior medial temporal lobes when using a 16-element surface coil array at 3 T (Tesla). Using this technique, the present study investigated the roles of the anterior medial temporal lobe, particularly the entorhinal and perirhinal cortices, in both object and spatial memory. Participants viewed a series of fractal images and were instructed to encode either the object's identity or location. Object and spatial recognition memory were tested after 18-sec delays. Both the perirhinal and entorhinal cortices were active during the object and spatial encoding tasks. In both regions, object encoding was biased to the left hemisphere, whereas spatial encoding was biased to the right. A similar hemispheric bias was evident for recognition memory. Recent animal studies suggest functional dissociations among regions of the entorhinal cortex for spatial vs. object processing. Our findings suggest that this process-specific distinction may be expressed in the human brain as a hemispheric division of labor.     

一体化促进联结记忆的作用机制：熟悉性和回想加工

当两个或两个以上项目进行一体化编码时, 熟悉性也能够支持联结再认, 这一观点已经得到大量研究证据的支持。然而, 关于一体化如何影响联结再认和构成联结的单个项目再认仍存在分歧。通过回顾现有研究发现：(1)一体化一致性是调节一体化与联结再认关系的重要因素; (2)认知资源有限和新/旧词语义相关性是影响一体化对项目再认作用的重要因素; (3)一体化的发生机制存在“项目假说”、“图式假说”以及“精细加工假说”三种可能的理论解释。未来研究不仅需要控制一体化一致性, 还可以比较不同一体化方式的作用大小以及探索一体化效应的毕生发展规律。     

Imaging the medial temporal lobe: exploring new dimensions

Cognitive scientists have used developments in functional imaging to explore the role of the medial temporal lobe (MTL) in memory formation. Lesion studies have suggested that separate MTL subregions make distinct contributions to memory. Functional imaging of these distinct contributions, however, remains a challenge, because the proximity of the MTL substructures tests the spatial resolution limits of current techniques. Recent findings using electrophysiological measures of neural activity highlight the importance of using information from other imaging modalities. Integrating the different modalities of neuroimaging with lesion studies, and, further, combining modalities within experiments, will provide new insights into the function of MTL subregions.     

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     

Single-item memory, associative memory, and the human hippocampus

We tested recognition memory for items and associations in memory-impaired patients with bilateral lesions thought to be limited to the hippocampal region. In Experiment 1 (Combined memory test), participants studied words and then took a memory test in which studied words, new words, studied word pairs, and recombined word pairs were presented in a mixed order. In Experiment 2 (Separated memory test), participants studied single words and then took a memory test involving studied word and new words. In a separate test, they studied word pairs and then took a memory test involving studied word pairs and recombined word pairs. In both experiments, patients were impaired at memory for single items as well as memory for associations, suggesting that the hippocampus is important for both of these memory functions. In Experiment 1, patients appeared to be more impaired at associative memory than item memory. In Experiment 2, patients were similarly impaired at associative memory and item memory. These different findings are considered, including the fact that in Experiment 1 the results depended on the fact that controls produced unexpectedly low false-alarm rates to recombined pairs. We discuss single-item and associative memory from the perspective that the hippocampus and adjacent cortex work cooperatively to signal recognition and that simple dichotomies do not adequately describe the division of labor within the medial temporal lobe.     

从认知神经的角度看内隐记忆和外显记忆的分离

当前的一些理论观点认为,内隐记忆和外显记忆依赖于两种不同的记忆系统,它们与大脑的不同区域相联系。该文通过回顾以往相关研究,从神经心理学及神经成像两方面对两种记忆系统的分离现象进行概述：在神经心理学领域发现的证据表明内隐记忆在神经解剖上与外显记忆是分离的;使用fMRI和PET技术,研究者观察到与内隐记忆有关的枕颞区及左下前额区中衰减的神经活动,以及与外显记忆有关的内侧颞区、前额皮层和后内侧顶皮层中增强的活动;使用ERP技术,研究也发现了两种记忆神经系统在时空上的不同特征     

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.     

The retrosplenial contribution to human navigation: a review of lesion and neuroimaging findings

The clinical and neuroimaging literatures are surveyed in order to collate for the first time the available data on retrosplenial involvement in human navigation. Several notable features emerge from consideration of the case reports of relatively pure topographical disorientation in the presence of a retrosplenial lesion. The majority of cases follow damage to the right retrosplenial cortex, with Brodmann's area 30 apparently compromised in most cases. All patients displayed impaired learning of new routes, and defective navigation in familiar environments complaining they could not use preserved landmark recognition to aid orientation. The deficit generally resolved within eight weeks of onset. The majority of functional neuroimaging studies involving navigation or orientation in large-scale space also activate the retrosplenial cortex, usually bilaterally, with good concordance in the locations of the voxel of peak activation across studies, again with Brodmann's area 30 featuring prominently. While there is strong evidence for right medial temporal lobe involvement in navigation, it now seems that the inputs the hippocampus and related structures receive from and convey to right retrosplenial cortex have a similar spatial preference, while the left medial temporal and left retrosplenial cortices seem primarily concerned with more general aspects of episodic memory.