Neural Activity in the Hippocampus and Perirhinal Cortex During Encoding Is Associated With the Durability of Episodic Memory

Studies examining medial temporal lobe (MTL) involvement in memory formation typically assess memory performance after a single, short delay. Thus, the relationship between MTL encoding activity and memory durability over time remains poorly characterized. To explore this relationship, we scanned participants using high-resolution functional imaging of the MTL as they encoded object pairs; using the remember/know paradigm, we then assessed memory performance for studied items both 10 min and 1 week later. Encoding trials were classified as either subsequently recollected across both delays, transiently recollected (i.e., recollected at 10 min but not after 1 week), consistently familiar, or consistently forgotten. Activity in perirhinal cortex (PRC) and a hippocampal subfield comprising the dentate gyrus and CA fields 2 and 3 reflected successful encoding only when items were recollected consistently across both delays. Furthermore, in PRC, encoding activity for items that later were consistently recollected was significantly greater than that for transiently recollected and consistently familiar items. Parahippocampal cortex, in contrast, showed a subsequent memory effect during encoding of items that were recollected after 10 min, regardless of whether they also were recollected after 1 week. These data suggest that MTL subfields contribute uniquely to the formation of memories that endure over time, and highlight a role for PRC in supporting subsequent durable episodic recollection

Episodic encoding is more than the sum of its parts: An fMRI investigation of multifeatural contextual encoding

Episodic memories are characterized by their contextual richness, yet little is known about how the various features comprising an episode are brought together in memory. Here we employed fMRI and a multidimensional source memory procedure to investigate processes supporting the mnemonic binding of item and contextual information. Volunteers were scanned while encoding items for which the contextual features (color and location) varied independently, allowing activity elicited at the time of study to be segregated according to whether both, one, or neither feature was successfully retrieved on a later memory test. Activity uniquely associated with successful encoding of both features was identified in the intra-parietal sulcus, a region strongly implicated in the support of attentionally mediated perceptual binding. The findings suggest that the encoding of disparate features of an episode into a common memory representation requires that the features be conjoined in a common perceptual representation when the episode is initially experienced

Activity in Both Hippocampus and Perirhinal Cortex Predicts the Memory Strength of Subsequently Remembered Information

SummaryIt has been suggested that hippocampal activity predicts subsequent recognition success when recognition decisions are based disproportionately on recollection, whereas perirhinal activity predicts recognition success when decisions are based primarily on familiarity. Another perspective is that both hippocampal and perirhinal activity are predictive of overall memory strength. We tested the relationship between brain activity during learning and subsequent memory strength. Activity in a number of cortical regions (including regions within the “default network”) was negatively correlated with subsequent memory strength, suggesting that this activity reflects inattention or mind wandering (and, consequently, poor memory). In contrast, activity in both hippocampus and perirhinal cortex positively correlated with the subsequent memory strength of remembered items. This finding suggests that both structures cooperate during learning to determine the memory strength of what is being learned

The Neural and Cognitive Basis of Cumulative Lifetime Familiarity Assessment

Perirhinal cortex (PrC) has been implicated as a brain region in the medial temporal lobes (MTL) that critically contributes to familiarity-based recognition memory, a process that allows for recognition to occur independently of contextual recollection. Informed by neurophysiological research in non-human primates, fMRI, as well as behavioural work in humans, the current thesis research tests the novel hypothesis that PrC cortex functioning also underlies the ability to assess cumulative lifetime familiarity with object concepts that are characterized by a lifetime of experiences. In Chapter 2, a patient (NB) with a left anterior temporal lobe (ATL) lesion that included PrC as well as an amnesic patient (HC) with a bilateral lesion to the hippocampus were tested on their ability to make lifetime familiarity judgements for object concepts (i.e., concrete nouns). Patient NB made abnormal familiarity ratings for objects concepts relative to matched controls, while patient HC produced ratings that did not differ from control participants. In Chapter 3, I tested healthy young adults on a frequency judgement task and lifetime familiarity task while they underwent fMRI. A region in the left PrC tracked both the perceived frequency of recent laboratory exposure as well as perceived lifetime familiarity. Finally, in Chapter 4, I tested whether indeed lifetime familiarity judgements are based on conceptual processing by making use of an associative priming paradigm. Associatively-related primes increased the perceived familiarity of object concepts while also reducing the latency of these judgements. Overall, the results from all three empirical chapters provides evidence that warrants an extension of PrC functioning to include the cumulative assessment of lifetime familiarity with object concepts

Content representation in the human medial temporal lobe

The transformation of sensory inputs into complex memory representations is fundamental to human experience; yet, little is known about how this crucial process is achieved. When you meet your friend at the new cafe in town, what part of the brain encodes this novel scene into long term memory? What part encoded your friend’s favorite t-shirt, so that the sight of it gives you a feeling of familiarity rather than surprise? It is well-established that the medial temporal lobe (MTL) is crucial to both processes, but the MTL is not a single homogeneous region. In fact, it is composed of several anatomically distinct subregions including hippocampus, perirhinal cortex (PRC) and parahippocampal cortex (PHC). However, the computations performed by each subregion to encode individual events is still unclear. The present research tests the central hypothesis that different forms of event content are transformed into memory by distinct subregions within the MTL. A critical barrier in the study of content representation thus far has been its focus on comparing univariate peak activations in a region to different stimulus materials. To go beyond this limited approach, we employed multivariate statistical analyses that takes into account how event content is represented by distributed activity in MTL subregions. First, we examine the content-specific contributions of MTL subregions to episodic encoding and retrieval. Then, we demonstrate how these distributed representations support memory-based prediction to resolve ambiguities in our environment.Neuroscienc

How event-based memories change as a function of forgetting and consolidation

Episodic memories are composed of multiple elements, from the people we encounter, the locations we visit, and the objects we interact with. These ‘episodes’ are thought to be stored in memory as coherent event representations and are associated with holistic recollection at retrieval, such that the retrieval of one element is dependent on the retrieval of all other elements from the same event. Evidence for this ‘dependency’ has been shown to emerge from the association between the event elements themselves. Critically, dependency is seen when participants learn three overlapping pairwise associations in a ‘closed-loop’, but not when participants learn only two out of the three possible associations in an ‘open-loop’, suggesting that all pairwise associations between event-elements need to be explicitly encoded for a coherent event representation to emerge. Here I asked whether the associative structure formed at encoding affects how event-based memories are retained over a period of forgetting and consolidation. Recently formed representations are susceptible to forgetting via interference and/or decay, but also undergo memory consolidation; becoming less susceptible to interference and/or decay. As such, retention for an event-based representation will reflect an interaction between forgetting and consolidation. This thesis presents evidence that closed-loops tend to be forgotten in an all-or-none manner, such that closed-loops are more likely to either be retained or forgotten in their entirety. In contrast, open-loops are associated with a more asymmetrical pattern of forgetting as a function of memory reactivation during sleep. Further, the thesis presents fMRI evidence that closed-loops continue to be retrieved in a coherent manner following a period of forgetting and consolidation. These findings suggest that the associative structure formed at encoding has a lasting impact on the coherence of the underlying memory representation

Category-Specific Item Recognition and the Medial Temporal Lobe

Much neuropsychological and neuroimaging research has been focused on the contributions of different medial temporal lobe (MTL) structures to recognition memory. The majority of these studies have linked perirhinal cortex (PrC) to item recognition, whereas the hippocampus and parahippocampal cortex (PhC) have primarily been associated with the recollection of contextual detail pertaining to a specific prior stimulus encounter. Here, I report results from three fMRI studies that examined the neural correlates of item recognition with a specific focus on the relationship between such signals and category-specific effects in the MTL. In Chapter 2, I reveal that category-specific representations in both PrC and PhC can be brought to bear on item recognition decisions. In Chapter 3, I examined the specific stimulus properties that determine the relative contributions of PrC and PhC to item recognition, with a focus on landmark suitability. The results from this study revealed item recognition signals for non-landmark objects in PrC and landmarks in PhC. In Chapter 4, I focused specifically on face recognition to characterize the manner in which PrC codes item-recognition signals and to further explore the issue of category-specificity with independent functional localizer data. Results from this study indicate that item recognition signals in PrC can be distributed across voxels with directionally heterogeneous response profiles. Further, these data also revealed that the voxels comprising these patterns respond preferentially to faces under passive viewing conditions. Taken together, these findings suggest that item recognition signals are represented in a distributed, category-specific manner within both PrC and PhC

Tangled Up in Confounds - Unravelling the Controversial Roles of MTL-structures in Familiarity and Recollection

Recognition memory is commonly divided into ‘knowing that you encountered something before’ (familiarity) and ‘remembering specific, accompanying details’ (recollection). To date, no consensus could be reached concerning the methodological validity, nor the neuronal correlates of familiarity and recollection within the medial temporal lobe. Specifically, a dual-process model and a multi-attribute hypothesis compete about the role of the hippocampus in solely recollection or both recollection and familiarity, while neither one provides conclusive arguments. The current paper aims at evaluation of the reasoning within this controversy and brings up a novel perspective as well as consequent research suggestions

Prior knowledge contribution to declarative learning. A study in amnesia, aging and Alzheimer's disease

L'étude expérimentale de la mémoire humaine a connu deux moments historiques dans les soixante dernières années. 1957 marque la découverte du rôle du lobe temporal interne bilatéral dans l'apprentissage conscient, déclaratif. 1997 marque la découverte de deux systèmes de mémoire déclarative, épisodique et sémantique. Ces découvertes résultent d'études de cas en neuropsychologie. Cette thèse s'inscrit dans la tradition neuropsychologique: sa genèse doit tout à un patient souffrant d'une forme atypique d'amnésie développementale, le patient KA. Son point de départ est une étude de cas approfondie, avec deux résultats surprenants. Malgré une amnésie sévère, KA dispose de connaissances sémantiques exceptionnelles. Par ailleurs, il montre des capacités préservées d'apprentissage explicite, mais uniquement pour des stimuli concrets, pas abstraits. En conséquence, cette thèse a exploré deux pistes de recherche. Premièrement, nous avons caractérisé les processus préservés d'apprentissage déclaratif et l'anatomie cérébrale chez ce patient. Deuxièmement, nous avons étudié le rôle des connaissances préalables dans l'apprentissage: comment ce que l'on sait influence ce dont nous nous souvenons ? Une première série d'expériences montre chez ce patient une atteinte sévère et sélective de l'ensemble du système hippocampique, alors que les structures sous- hippocampiques (cortex entorhinal, périrhinal et parahippocampique) sont préservées. Malgré une amnésie épisodique sévère, nous montrons des connaissances sémantiques supranormales et des aptitudes d'apprentissage explicite rapide. Ces aptitudes sont toutefois restreintes aux stimuli associés à des connaissances préalables. Une seconde série d'expériences explore l'hypothèse selon laquelle les connaissances préalables facilitent l'apprentissage en mémoire déclarative, même dans les situations où le lobe temporal interne est fragilisé, comme dans le vieillissement, ou lésé, comme chez le patient KA ou dans la maladie d'Alzheimer. Nos résultats suggèrent l'existence de processus d'apprentissage rapide en mémoire déclarative, indépendants du système hippocampique et sensibles à la présence de représentations préexistantes. Ces processus semblent affectés par la maladie d'Alzheimer, et ce en lien avec un défaut d'activité des régions sous-hippocampiques antérieures. A l'inverse, les sujets âgés sains peuvent utiliser les connaissances préalables et pourraient ainsi compenser le déclin de la mémoire associative. Ce travail s'accorde avec les modèles postulant une dissociation fonctionnelle au sein du lobe temporal interne pour l'apprentissage déclaratif. Il soutient les propositions neurocognitives et computationnelles récentes, suggérant une voie d'apprentissage néocortical rapide mobilisable dans certaines circonstances. Il met en exergue la dynamique des apprentissages en mémoire déclarative et notamment l'intrication fondamentale entre "savoir" et "se souvenir". Ce que je sais a un impact profond sur ce dont je vais me souvenir. Cette thèse permet d'envisager de nouveaux outils cognitifs pour le diagnostic de la maladie d'Alzheimer. De plus, il semble que des lésions temporales internes auront un impact distinct sur l'apprentissage selon le statut des informations à mémoriser en mémoire à long terme, offrant un regard nouveau sur les effets stimulus-dépendants dans l'amnésie. Une considération approfondie des connaissances préalables associées au contenu de nos expériences, et leur caractérisation détaillée, est requise pour affiner les modèles de la mémoire déclarative. Ces résultats apportent de nouvelles pistes de recherche quant aux circonstances épargnant l'apprentissage, notamment associatif, lors du vieillissement. Plus généralement, ils contribuent à la compréhension des déterminants d'un apprentissage réussi, en mettant l'accent sur les recouvrements entre processus de récupération et d'acquisition. Des applications potentielles en découlent dans le domaine éducatif.The experimental study of human memory has had two historic moments in the last sixty years. 1957 marks the discovery of the role of the medial temporal lobes in conscious learning. 1997 marks the discovery of two systems of declarative memory, namely episodic and semantic memories. These major breakthroughs are owed to clinical case studies in neuropsychology. This thesis follows on from the neuropsychological tradition: its genesis owes everything to a patient suffering from an atypical form of developmental amnesia, the patient KA. The starting point of this work was a thorough neuropsychological study of this patient. Two striking findings shortly arose. First, despite lifelong amnesia, KA had acquired exceptional levels of knowledge about the world. Second, remaining explicit learning abilities were restricted to meaningful, not meaningless, memoranda. As a consequence, we have investigated two research pathways in that thesis. First, we aimed at better characterizing preserved learning abilities and brain structure of the patient KA. Second, our goal was to explore how prior knowledge affects new declarative learning or, put simply, how do we learn what we know? In a first series of behavioural and neuroimaging experiments, we have shown in this patient a severe and selective damage of the whole extended hippocampal system, but preserved subhippocampal structures (entorhinal, perirhinal and parahippocampal cortex). The patient suffers from severe episodic amnesia, but we bring striking evidence for supranormal semantic knowledge as well as normal explicit learning skills. These skills were, however, restricted to familiar stimuli, that is, stimuli carrying pre-experimental knowledge. In a second series of behavioural and neuroimaging experiments, we explored the hypothesis that prior knowledge can facilitate new learning in declarative memory, even in aging or in situations where structures of the medial temporal lobe are or injured, as in amnesia or Alzheimer's disease. Our results suggest the existence of processes allowing fast learning in declarative memory, independently of the hippocampal system, and that are sensitive to the presence of pre-existing representations in long-term memory. Such learning processes appear to be selectively affected by Alzheimer's disease at the pre-dementia stage, in relation to a lack of activation of subhippocampal regions. In contrast, healthy elderly were able to rely on these learning processes to compensate for the decline in associative memory associated with aging. This work lends support to the models postulating a functional dissociation with respect to learning in declarative memory. It indeed strengthens recent neurocognitive and computational accounts that suggest a rapid neocortical learning path under certain circumstances. It highlights the dynamics of learning in declarative memory and in particular the fundamental entanglement between "knowing" and "remembering". What I know profoundly impacts what I will remember. The present thesis points towards new cognitive tools for the diagnosis of Alzheimer's disease. It further brings evidence that medial temporal lesions differentially impact learning depending on the status of the memoranda in long-term memory, which sheds a new light on material-specific effects in amnesia. Our work speaks for a thorough consideration of whether the contents of events have prior representations within long-term memory, and to further better characterize their nature if we are to better understand learning mechanisms. It also brings additional clues for a deeper understanding of how learning and memory can be preserved in aging. More generally, it contributes to a better understanding of the factors determining successful learning, with a focus on how retrieval and acquisition processes overlap during learning. Such findings have potential applications in the educational field