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.     

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.     

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.     

Contributions of the medial temporal lobe to declarative memory retrieval: manipulating the amount of contextual retrieval

We investigated how the hippocampus and its adjacent mediotemporal structures contribute to contextual and noncontextual declarative memory retrieval by manipulating the amount of contextual information across two levels of the same contextual dimension in a source memory task. A first analysis identified medial temporal lobe (MTL) substructures mediating either contextual or noncontextual retrieval. A linearly weighted analysis elucidated which MTL substructures show a gradually increasing neural activity, depending on the amount of contextual information retrieved. A hippocampal engagement was found during both levels of source memory but not during item memory retrieval. The anterior MTL including the perirhinal cortex was only engaged during item memory retrieval by an activity decrease. Only the posterior parahippocampal cortex showed an activation increasing with the amount of contextual information retrieved. If one assumes a roughly linear relationship between the blood-oxygenation level-dependent (BOLD) signal and the associated cognitive process, our results suggest that the posterior parahippocampal cortex is involved in contextual retrieval on the basis of memory strength while the hippocampus processes representations of item-context binding. The anterior MTL including perirhinal cortex seems to be particularly engaged in familiarity-based item recognition. If one assumes departure from linearity, however, our results can also be explained by one-dimensional modulation of memory strength.     

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.     

Color and context: An ERP study on intrinsic and extrinsic feature binding in episodic memory

Episodic memory for intrinsic item and extrinsic context information is postulated to rely on two distinct types of representation: object and episodic tokens. These provide the basis for familiarity and recollection, respectively. Electrophysiological indices of these processes (ERP old-new effects) were used together with behavioral data to test these assumptions. We manipulated an intrinsic object feature (color; Experiment 1) and a contextual feature (background; Experiments 1 and 2). In an inclusion task (Experiment 1), the study-test manipulation of color affected object recognition performance and modulated ERP old-new effects associated with both familiarity and recollection. In contrast, a contextual manipulation had no effect, although both intrinsic and extrinsic information was available in a direct feature (source memory) test. When made task relevant (exclusion task; Experiment 2), however, context affected the ERP recollection effect, while still leaving the ERP familiarity effect uninfluenced. We conclude that intrinsic features bound in object tokens are involuntarily processed during object recognition, thus influencing familiarity, whereas context features bound in episodic tokens are voluntarily accessed, exclusively influencing recollection. Figures depicting all the electrodes analyzed are available in an online supplement at www.psychonomic.org/archive.     

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.     

Is associative recognition more impaired than item recognition memory in Schizophrenia? A meta-analysis

Item recognition memory judgment can be based on two processes: item familiarity and/or the conscious recollection of the initial event. On the other hand, associative recognition relies preferably on conscious recollection. Since evidence points to a specific deficit of conscious recollection in schizophrenia, these patients could show greater impairment during associative recognition tasks relative to item recognition tasks. A meta-analysis of 23 studies of recognition memory in schizophrenia was conducted to test this hypothesis. The impairment is indeed 20% greater (p=0.04) for associative recognition relative to item recognition. This study supports the hypothesis of a specific conscious recollection deficit underlying episodic memory impairment in schizophrenia.     

Associative recognition processes are modulated by the semantic unitizability of memoranda

Although memory of episodic associations is generally considered to be recollective in nature, it has been suggested that when stimuli are experienced as a unit, familiarity processes might contribute to their subsequent associative recognition. To investigate the effect of semantic relatedness during episodic encoding on the processes of retrieval of associative information, we had participants interactively encode pairs of object pictures, vertically arranged so as to suggest a functional or configural relationship between them. Half the pairs were independently judged to be of related objects (e.g., a lamp over a table) and half of unrelated objects (e.g., a key-ring over an apple). At test, participants discriminated between intact, recombined, and new pairs while event related potentials (ERPs) were recorded. In an early ERP marker of retrieval success generally associated with familiarity processes, differences related to associative memory only emerged for related pairs, while differences associated with item memory emerged for both related and unrelated pairs. In contrast, in a later ERP effect associated with recollection, differences related to associative memory emerged for both related and unrelated pairs. These findings may indicate that retrieval of episodic associations formed between two semantically related visual stimuli can be supported by familiarity-related processes.     

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.     

Recognition memory and prefrontal cortex: dissociating recollection and familiarity processes using rTMS

Recognition memory can be supported by both the assessment of the familiarity of an item and by the recollection of the context in which an item was encountered. The neural substrates of these memory processes are controversial. To address these issues we applied repetitive transcranial magnetic stimulation (rTMS) over the right and left dorsolateral prefrontal cortex (DLPFC) of healthy subjects performing a remember/know task. rTMS disrupted familiarity judgments when applied before encoding of stimuli over both right and left DLPFC. rTMS disrupted recollection when applied before encoding of stimuli over the right DLPFC. These findings suggest that the DLPFC plays a critical role in recognition memory based on familiarity as well as recollection.     

跨领域项目间联结记忆中项目提取和关系提取的分离：一项事件相关电位研究

使用ERPs技术, 探讨跨领域项目间联结记忆中项目提取和关系提取的差异。学习阶段, 系列呈现面孔-事件动词材料, 让被试识记面孔、事件动词以及两者之间的关系; 测验阶段, 要求被试对成对刺激进行“相同”、“重组”或“新”判断。结果发现：提取阶段, 刺激呈现后约200 ms, “相同”、“重组”和“新”3种条件下的ERPs开始出现分离, 存在“相同/新”、“重组/新”和“相同/重组”三类新旧效应。在200~300 ms, “相同/新”和“重组/新”两类新旧效应表现在前额和额区皮层; 在300~500 ms, 这两类新旧效应广泛地分布在从前到后各个脑区皮层; 在500~700 ms, “相同/新”新旧效应出现在额-顶区皮层, 而无“重组/新”新旧效应; 在700~1400 ms, 这两类新旧效应发生在前额和额区皮层; 在上述4个时段, “相同/重组”关系新旧效应都发生在额中-中央-顶区皮层。从这些结果可以推知：跨领域项目间联结再认中, 项目新旧效应和关系新旧效应同时出现, 但是关系提取比项目提取较晚完成; 额中-中央-顶区皮层关系新旧效应反映了对项目间关系的回忆加工; 而700 ms以后, 前额、额区皮层新旧效应可能反映了项目之间关系提取过程的执行加工功能。     

不同情绪背景下来源记忆的ERPs研究*

使用事件相关电位(ERP)技术和测试来源记忆的多键范式,探讨不同情绪效价背景下来源提取的认知神经机制。学习阶段,同时呈现汉字和3种效价情绪图片(重叠);测验阶段,只呈现汉字,要求被试进行四键判断：旧字且背景为中性,旧字且背景为正性,旧字且背景为负性,新字。结果发现：在提取阶段,刺激呈现后300~500 ms,3种情绪背景下来源判断正确项目和来源判断错误项目都比新项目诱发了更正的ERPs(即都存在新旧效应),这一结果反映出刺激呈现后300~500 ms 是一个早期的项目提取阶段,它独立于来源提取。并且,在中性背景下,两种新旧效应没有差别;而在正性和负性背景下,来源判断正确项目的新旧效应显著大于来源判断错误项目。说明相比于中性背景,情绪背景下被试可能更早对来源信息产生熟悉感。在500~650 ms,3种情绪背景下都存在来源判断正确项目的新旧效应,在来源判断错误项目和新项目之间没有显著差异,来源正确与来源错误有显著的新旧效应差异,但二者在头皮分布上是类似的,这反映了晚期的来源提取过程。同时来源正确的新旧效应在这两个时段有显著不同的头皮分布,表明这两个时段有不同加工过程。另外,在500~650 ms,存在显著的情绪效应,正性背景下正确判断来源诱发的ERPs比中性和负性背景下的更正,而且来源判断错误条件下没有情绪效应。综上所述,来源正确和来源错误可能仅仅反映了大脑激活在量上的不同,并不能推断两者存在质的差异;大脑神经活动的早期不仅反映了对记忆项目的熟悉性,而且也受情绪效应的影响,500 ms之后大脑神经活动反映的是对记忆项目回想的过程,这一回想过程也与情绪效应有关,受到情绪效应的调节。     

物体颜色对情景记忆的影响

本研究采用ERP技术和学习-再认范式考察视觉输入的颜色和记忆中的物体颜色知识一致性对情景记忆编码和提取的影响。结果显示, 在对物体图片进行编码时颜色不一致图片诱发更大N400, 而提取阶段则对颜色一致图片有更多熟悉性加工(实验1); 物体名称能够更快激活典型颜色知识, 对颜色一致名称有更多细节回想(LPC更正) (实验2)。实验结果表明, 颜色一致促进知觉水平的记忆编码, 而阻碍语义水平编码。同时, 颜色一致促进物体图片提取(知觉水平)中的熟悉性和回想过程; 而对物体名称提取(概念水平)的促进作用仅表现在回想上。此外, 颜色与物体名称有着密切联系, 同样影响物体的语义表征, 支持激活-扩散模型理论。本研究从知觉和概念水平上为揭示物体颜色在联结记忆中的作用提供了证据。     

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     

Effects of modality on the neural correlates of encoding processes supporting recollection and familiarity

Prior research has demonstrated that the neural correlates of successful encoding ("subsequent memory effects") partially overlap with neural regions selectively engaged by the on-line demands of the study task. The primary goal of the present experiment was to determine whether this overlap is associated solely with encoding processes supporting later recollection, or whether overlapping subsequent memory and study condition effects are also evident when later memory is familiarity-based. Subjects (N = 17) underwent fMRI scanning while studying a series of visually and auditorily presented words. Memory for the words was subsequently tested with a modified Remember/Know procedure. Auditorily selective subsequent familiarity effects were evident in bilateral temporal regions that also responded preferentially to auditory items. Although other interpretations are possible, these findings suggest that overlap between study condition-selective subsequent memory effects and regions selectively sensitive to study demands is not uniquely associated with later recollection. In addition, modality-independent subsequent memory effects were identified in several cortical regions. In every case, the effects were greatest for later recollected items, and smaller for items later recognized on the basis of familiarity. The implications of this quantitative dissociation for dual-process models of recognition memory are discussed.     

ROC in animals: Uncovering the neural substrates of recollection and familiarity in episodic recognition memory

It is a consensus that familiarity and recollection contribute to episodic recognition memory. However, it remains controversial whether familiarity and recollection are qualitatively distinct processes supported by different brain regions, or whether they reflect different strengths of the same process and share the same support. In this review, I discuss how adapting standard human recognition memory paradigms to rats, performing circumscribed brain lesions and using receiver operating characteristic (ROC) methods contributed to solve this controversy. First, I describe the validation of the animal ROC paradigms and report evidence that familiarity and recollection are distinct processes in intact rats. Second, I report results from rats with hippocampal dysfunction which confirm this finding and lead to the conclusion that the hippocampus supports recollection but not familiarity. Finally, I describe a recent study focusing on the medial entorhinal cortex (MEC) that investigates the contribution of areas upstream of the hippocampus to recollection and familiarity.     

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.     

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 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.