Neural Correlates Of Episodic Memory Formation In Children And Adults

The medial temporal lobe (MTL) and prefrontal cortex (PFC) are two key brain regions that support episodic memory formation in both children and adults, but the functional developmental of these regions remains unclear. In this study, we investigated the development of neural correlates of episodic memory formation using functional MRI with a subsequent memory paradigm, administered to a cross-sectional sample of 83 children and adults. We found that MTL subregions showed an age-related increase in activation supporting memory formation of complex scenes. In addition, a functionally defined scene-sensitive region in the posterior MTL also showed similar increase and predicted better memory for complex scenes. Within the PFC we found age-related increase in both activation and deactivation that support memory formation. Finally, we found age-related increase in the functional connectivity between dorsal lateral PFC and posterior MTL regions. Taken together, these findings suggest that the continued functional development of the MTL and the PFC is crucial for age-related improvements in memory

Towards Improving Learning with Consumer-Grade, Closed-Loop, Electroencephalographic Neurofeedback

Learning is an enigmatic process composed of a multitude of cognitive systems that are functionally and neuroanatomically distinct. Nevertheless, two undeniable pillars which underpin learning are attention and memory; to learn, one must attend, and maintain a representation of, an event. Psychological and neuroscientific technologies that permit researchers to “mind-read” have revealed much about the dynamics of these distinct processes that contribute to learning. This investigation first outlines the cognitive pillars which support learning and the technologies that permit such an understanding. It then employs a novel task—the amSMART paradigm—with the goal of building a real-time, closed-loop, electroencephalographic (EEG) neurofeedback paradigm using consumergrade brain-computer interface (BCI) hardware. Data are presented which indicate the current status of consumer-grade BCI for EEG cognition classification and enhancement, and directions are suggested for the developing world of consumer neurofeedback

The effects of structural and functional damage to limbic structures on cognitive abilities

Functional and degenerative damage to regions of the limbic system are often associated with cognitive impairments in different aspects of memory. Neuroimaging studies in post-traumatic stress disorder (PTSD) and Alzheimer’s disease (AD) have reported selective hippocampal atrophy. Neuroimaging studies in panic disorder have also suggested reduced functional activity in the right parahippocampal gyrus. It is unclear whether this hippocampal damage is responsible for the emergence of selective neuropsychological deficits. Abnormal activity in limbic structures has also been reported in PTSD patients exposed to trauma-related stimuli. This thesis was concerned with examining the effects of structural and functional damage to the limbic system on selective cognitive abilities. The limbic structures under investigation included the hippocampus, parahippocampal gyrus, anterior cingulate cortex and amygdala. In order to investigate this issue, a series of neuropsychological and neuroimaging experiments were carried out using groups of patient populations, such as panic disorder, PTSD and AD, known to exhibit abnormalities to the limbic structures. An fMRI study, using the Color Stroop and Emotional Stroop task was also administered to PTSD patients and healthy controls.Results from the neuropsychological studies showed greater impairments in topographical/spatial memory compared to verbal memory in all groups of patients. In addition, voxel-based correlation analyses found that both PTSD and AD are associated with neuropsychological deficits in the area of visuo-spatial and topographical memory that may be explained by the regional brain atrophy in limbic structures. Abnormalities of the parahippocampal gyri and cingulate cortex and possibly the amygdalae in the fMRI study also suggested a dysregulation in limbic-cortical networks in PTSD. This thesis has demonstrated that damage to limbic structures might contribute to the cognitive abnormalities of panic disorder, PTSD and AD

Allocentric memory and hippocampal function

PhD ThesisApproximately one-third of trauma patients are coagulopathic on arrival to the emergency department. Acute traumatic coagulopathy and systemic inflammatory responses are serious secondary consequences of severe trauma and are linked to increased morbidity and mortality. Early tissue hypoxia is a major component in the aetiology of both complications. New resuscitation strategies are aimed at improving tissue oxygenation in the pre-hospital phase, and may attenuate coagulopathy and inflammatory sequelae. This is of particular importance in military personnel who suffer complex injuries, often from blast exposure, and may have extended evacuation times. This thesis evaluates the effect of a novel hybrid (NH) resuscitation strategy on coagulation and inflammation. Terminally anaesthetised pigs were randomised to one of two injury strands of haemorrhage +/- blast injury; initially resuscitated with 0.9% Saline to a hypotensive systolic blood pressure of 80mmHg for one hour. This was followed by either a return to a normotensive pressure (110mmHg) (NH) or a continuation at the hypotensive level. Over both injury strands NH significantly reduced Prothrombin Time, PT (mean proportion of baseline: 1.40±0.05 vs. 1.80±0.09; p=0.001) and interleukin-6 (IL6) levels (mean 1106±153 vs. 429±79 pg/ml; p=0.001) compared to the hypotensive groups. PT was positively correlated with IL6 (p=0.002) and base deficit (p=0.0004). These findings indicate that improving tissue oxygenation reduces the coagulation derangement and the pro-inflammatory response. No difference in coagulopathy was found between injury strands although blast did cause greater inflammation. Early identification of coagulopathic casualties is essential and a separate feasibility field study was preformed to assess the use of thromboelastometry in a deployed military hospital, evaluating the degree of coagulopathy in battlefield casualties and to monitor the coagulation status during the resuscitation process. In conclusion, NH attenuated the acute traumatic coagulopathy and inflammatory responses and therefore should be considered when an extended casualty evacuation is enforced

Neural processes underpinning episodic memory

Episodic memory is the memory for our personal past experiences. Although numerous functional magnetic resonance imaging (fMRI) studies investigating its neural basis have revealed a consistent and distributed network of associated brain regions, surprisingly little is known about the contributions individual brain areas make to the recollective experience. In this thesis I address this fundamental issue by employing a range of different experimental techniques including neuropsychological testing, virtual reality environments, whole brain and high spatial resolution fMRI, and multivariate pattern analysis. Episodic memory recall is widely agreed to be a reconstructive process, one that is known to be critically reliant on the hippocampus. I therefore hypothesised that the same neural machinery responsible for reconstruction might also support ‘constructive’ cognitive functions such as imagination. To test this proposal, patients with focal damage to the hippocampus bilaterally were asked to imagine new experiences and were found to be impaired relative to matched control participants. Moreover, driving this deficit was a lack of spatial coherence in their imagined experiences, pointing to a role for the hippocampus in binding together the disparate elements of a scene. A subsequent fMRI study involving healthy participants compared the recall of real memories with the construction of imaginary memories. This revealed a fronto-temporo-parietal network in common to both tasks that included the hippocampus, ventromedial prefrontal, retrosplenial and parietal cortices. Based on these results I advanced the notion that this network might support the process of ‘scene construction’, defined as the generation and maintenance of a complex and coherent spatial context. Furthermore, I argued that this scene construction network might underpin other important cognitive functions besides episodic memory and imagination, such as navigation and thinking about the future. It is has been proposed that spatial context may act as the scaffold around which episodic memories are built. Given the hippocampus appears to play a critical role in imagination by supporting the creation of a rich coherent spatial scene, I sought to explore the nature of this hippocampal spatial code in a novel way. By combining high spatial resolution fMRI with multivariate pattern analysis techniques it proved possible to accurately determine where a subject was located in a virtual reality environment based solely on the pattern of activity across hippocampal voxels. For this to have been possible, the hippocampal population code must be large and non-uniform. I then extended these techniques to the domain of episodic memory by showing that individual memories could be accurately decoded from the pattern of activity across hippocampal voxels, thus identifying individual memory traces. I consider these findings together with other recent advances in the episodic memory field, and present a new perspective on the role of the hippocampus in episodic recollection. I discuss how this new (and preliminary) framework compares with current prevailing theories of hippocampal function, and suggest how it might account for some previously contradictory data

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

Effects of Social and Non-Social Interpretations of Complex Images on Human Eye Movement and Brain Activation

Communicating and interacting with others is an essential part of our daily routines as humans. Performing these actions appropriately requires the ability to identify, extract, and process salient social cues from the environment. The subsequent application of such knowledge is important for inferring and predicting the behavior of other people. The eyes and brain must work together to fixate and process only the most critical social signals within a scene while passing over and / or completely ignoring other aspects of the scene. While brain activation to isolated presentations of objects and people presentations have been characterized, information about the brain\u27s activation patterns to more comprehensive scenes containing multiple categories of information is limited. Furthermore, little is known about how different interpretations of a scene might alter how that scene is viewed or how the brain responds to that scene. Therefore, the studies presented herein used a combination of infrared eye tracking and functional magnetic resonance imaging techniques to investigate the eye movement and brain activation patterns to socially- and non-socially-relevant interpretations of the same set of complex stimuli. Eye tracking data showed that each gaze pattern was consistent with viewing and attending to only one category of information (people or objects) despite both categories being present in all images. Functional magnetic resonance imaging revealed that a region of the right superior temporal sulcus was selectively activated by the social condition compared to the non-social condition, an area known for its role in social tasks. Brain activation in response to the non-social condition was located in many of the same regions associated with the recognition and processing of visual objects presented in isolation. Taken together, these results demonstrate that in healthy adults, eye movement and brain activation patterns to identical scenes change markedly as a function of attentional focus and interpretation intention. Utilizing realistic and complex stimuli to study the eye gaze and neural activation patterns associated with processing social versus non-social information in the healthy brain is an important step towards understanding the deficits present in individuals with social cognition disorders like autism and schizophrenia