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See detail[18F]UCB-H AS A BRAIN SV2A RADIOTRACER: A FIRST CLINICAL TRIAL
Bahri, Mohamed Ali ULg; Bastin, Christine ULg; Aerts, Joël ULg et al

Poster (2014, May 27)

[18F]UCB-H is a fluorine-18 radiolabelled PET imaging tracer with a high affinity for the synaptic vesicle protein 2A (SV2A). This protein, involved in vesicle trafficking and widely distributed in the ... [more ▼]

[18F]UCB-H is a fluorine-18 radiolabelled PET imaging tracer with a high affinity for the synaptic vesicle protein 2A (SV2A). This protein, involved in vesicle trafficking and widely distributed in the brain, represents the binding site and the primary mechanism of the antiepileptic drug levetiracetam. Levetiracetam has recently been suggested to reduce synaptic deficits in a mouse Alzheimer’s disease model and to improve cognition in patients with amnestic mild cognitive impairment, suggesting a possible role for this protein in synaptic integrity. The objective of this study was to investigate the cerebral distribution of [18F]UCB-H in healthy human volunteers. Dynamic PET imaging of the head of four healthy volunteers was performed over 100 minutes after injection of 170.4 ± 24.9 MBq of GMP produced [18F]UCB-H. The input function was acquired by arterial blood sampling during the dynamic PET acquisition. Blood data analysis showed a consistent tracer amount in whole blood and plasma indicating a very low degree of binding of the tracer to the red blood cells. Unchanged [18F]UCB-H fraction in plasma follows a bi-exponential behavioral decrease with a starting fraction of 92% of the injected amount of the tracer, measured at 3 min post injection. This fraction decreases to about 50% at 10 min post injection. The [18F]UCB-H PET data revealed a high and rapid uptake in the grey matter structures, matching the known ubiquitous distribution of SV2A in the brain. The kinetics of the tracer in the brain was characterized by an initial high uptake phase followed by rapid washout allowing the standard compartmental modeling (1-tissue compartment, 2-tissue compartment, and Logan graphical analysis). The three models gave consistent results. The two-tissue compartment model fitted the experimental data best and provided a total distribution volume of [18F]UCB-H in the brain greater than 7 mL/cm3 and a specific distribution volume around 3 mL/cm3. Our results indicate that [18F]UCB-H is a new radiotracer for brain SV2A proteins suitable for human studies. Further studies are warranted to assess SV2A modifications in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailThe Neural Correlates of Re-cancellation Behaviors in Unilateral Neglect: A Neuropsychological Approach
Wansard, Murielle ULg; Bastin, Christine ULg; Meulemans, Thierry ULg

Poster (2014, April)

The present study focused on re-cancellation behaviors in unilateral neglect (i.e., the tendency to search repeatedly items located on the right side in visual search tasks), and used a neuropsychological ... [more ▼]

The present study focused on re-cancellation behaviors in unilateral neglect (i.e., the tendency to search repeatedly items located on the right side in visual search tasks), and used a neuropsychological approach to identify the cerebral correlates of this deficit. Fourteen patients suffering from left neglect and 14 elderly age-matched controls performed a cancellation task without visual feedback. Neglect patients cancelled fewer targets than controls, and re-cancelled an abnormally high number of targets. Lesion maps were used to compare the location of brain damage in neglect patients with the highest versus the lowest percentage of re-cancellations. Anatomical data revealed that the right insula is commonly damaged in 5 out of 6 patients with the highest re-cancellation percentage, but is spared in the subgroup of patients with the lowest re-cancellation percentage. These results suggest that damage to the right insula may contribute to pathological visual search in spatial neglect, possibly by reducing interaction between the ventral and dorsal attention network (the latter being more directly involved in spatial processes). [less ▲]

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See detailEarly neuropsychological detection of Alzheimer's disease
Bastin, Christine ULg

Conference (2014, March 06)

Considering that brain pathology due to Alzheimer’s disease starts many years before the clinical symptoms become evident, subtle cognitive changes may exist already in the predementia phase. Different ... [more ▼]

Considering that brain pathology due to Alzheimer’s disease starts many years before the clinical symptoms become evident, subtle cognitive changes may exist already in the predementia phase. Different approaches have been used to detect initial cognitive impairments indicative of Alzheimer’s disease. One approach is the assessment of the predictive power of neuropsychological tools in characterizing patients with stable mild cognitive impairment (MCI) versus MCI patients who subsequently develop Alzheimer’s disease. Another approach is the longitudinal evaluation of large cohorts of older adults in population-based studies. Findings from several studies suggest that a memory test that ensures deep encoding of information and assesses retrieval with free as well as cued recall is a useful tool to distinguish patients at an early stage of Alzheimer disease from MCI non-converters. Impaired semantic memory has also been proposed as a neuropsychological marker of predementia Alzheimer’s disease. Beyond the memory domain, category verbal fluency has been shown to predict progression to Alzheimer’s disease. Moreover, combining neuropsychological scores of memory and executive functions and neuroimaging data allows a better discrimination between stable MCI and converters than neuroimaging data alone. Altogether, it is possible to detect cognitive changes that are predictive of the typical form of probable Alzheimer’s disease already in the predementia stage. Such at risk people are thought to be the best target for therapeutic interventions. [less ▲]

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See detailCombining PET images and neuropsychological test data for automatic diagnosis of Alzheimer’s disease
Segovia-Román, Fermín ULg; Bastin, Christine ULg; Salmon, Eric ULg et al

in PLoS ONE (2014), 9(2),

In recent years, several approaches to develop computer aided diagnosis (CAD) systems for dementia have been proposed. Some of these systems analyze neurological brain images by means of machine learning ... [more ▼]

In recent years, several approaches to develop computer aided diagnosis (CAD) systems for dementia have been proposed. Some of these systems analyze neurological brain images by means of machine learning algorithms in order to find the patterns that characterize the disorder, and a few combine several imaging modalities to improve the diagnostic accuracy. However, they usually do not use neuropsychological testing data in that analysis. The purpose of this work is to measure the advantages of using not only neuroimages as data source in CAD systems for dementia but also neuropsychological scores. To this aim, we compared the accuracy rates achieved by systems that use neuropsychological scores beside the imaging data in the classification step and systems that use only one of these data sources. In order to address the small sample size problem and facilitate the data combination, a dimensionality reduction step (implemented using three different algorithms) was also applied on the imaging data. After each image is summarized in a reduced set of image features, the data sources were combined and classified using three different data combination approaches and a Support Vector Machine classifier. That way, by testing different dimensionality reduction methods and several data combination approaches, we aim not only highlighting the advantages of using neuropsychological scores in the classification, but also implementing the most accurate computer system for early dementia detention. The accuracy of the CAD systems were estimated using a database with records from 46 subjects, diagnosed with MCI or AD. A peak accuracy rate of 89% was obtained. In all cases the accuracy achieved using both, neuropsychological scores and imaging data, was substantially higher than the one obtained using only the imaging data. [less ▲]

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See detailEffet de l’âge et du type d’encodage en mémoire épisodique
Hagelstein, Catherine; François, Sarah ULg; Manard, Marine ULg et al

Poster (2014)

Introduction. Lors du vieillissement, on observe une diminution des capacités mémoire épisodique (a), se caractérisant par une diminution de la recollection (b). Dans cette étude, nous nous sommes ... [more ▼]

Introduction. Lors du vieillissement, on observe une diminution des capacités mémoire épisodique (a), se caractérisant par une diminution de la recollection (b). Dans cette étude, nous nous sommes intéressés à l'influence des consignes d'encodage, intentionnelles ou incidentes, sur la performance de participants jeunes et âgés à une tâche de mémoire épisodique. Méthodologie. Vingt volontaires jeunes (18-30 ans) et 20 volontaires âgés (61-72 ans) ont participé à cette expérience. Le matériel se composait de 300 dessins en noir et blanc représentant des objets de la vie courante. La tâche se déroulait en deux étapes. Lors de la phase d'encodage, 100 items étaient présentés une seule fois (condition «difficile») et 100 autres items étaient présentés deux fois (condition «facile»). Lors de la reconnaissance, les items de la phase d’encodage étaient à nouveaux présentés, ainsi que 100 nouveaux items. Dans chaque groupe d'âge, la moitié des participants effectuait la tâche d'encodage en recevant une consigne d'encodage incident (jugement sur la taille de l'objet) tandis qu'il était explicitement demandé à l'autre moitié de mémoriser les objets qui leur étaient présentés en vue d'un test de mémoire (encodage intentionnel). Lors de la reconnaissance, les participants effectuaient un jugement de type Recollection-Familiarité pour les items qu'ils estimaient avoir vu précédemment. Nous avons réalisé des ANOVAs afin de tester l'influence des consignes, du groupe d'âge et du nombre de répétitions de l'item d'une part sur le pourcentage de réponses de type Recollection et d'autre part sur le pourcentage de réponses de type Familiarité (p<0,05). Résultats et discussion. Les analyses montrent un effet significatif de l'âge, avec un pourcentage de réponses correctes de type "recollection" plus élevé chez les sujets jeunes, tandis qu'on observe un plus grand pourcentage de réponses correctes de type "familiarité" chez les sujets âgés. De plus, les résultats montrent que les stimuli présentés deux fois produisent plus de réponses de type "recollection" que ceux présentés une seule fois. Finalement, les données suggèrent également que, pour la condition "facile" uniquement, dans le groupe de sujets âgés, les consignes d'encodage intentionnel mènent à plus de recollection et moins de familiarité. Ces résultats sont compatibles avec les travaux montrant que les personnes âgées ont des difficultés à mettre spontanément en place des stratégies d'encodage élaboré, et qu'elles ont besoin de davantage de soutien (ici sous la forme d'une deuxième exposition au matériel) pour mener à bien un encodage profond lorsqu'elles y sont encouragées par des instructions d'apprentissage intentionnel (c). Références (a) Cappell, K. A., Gmeindl, L., & Reuter-Lorenz, P. A. (2010). Age differences in prefontal recruitment during verbal working memory maintenance depend on memory load. Cortex, 46(4), 462-473. doi: 10.1016/j.cortex.2009.11.009 (b) Bugaiska, A., Clarys, D., Jarry, C., Taconnat, L., Tapia, G., Vanneste, S., & Isingrini, M. (2007). The effect of aging in recollective experience: the processing speed and executive functioning hypothesis. Consciousness and Cognition, 16(4), 797-808. doi: 10.1016/j.concog.2006.11.007 (c) Froger, C., Bouazzaoui, B., Isingrini, M., & Taconnat, L. (2012). Study time allocation deficit of older adults: the role of environmental support at encoding? Psychology and Aging, 27(3), 577-588. doi: 10.1037/a0026358 [less ▲]

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See detailEffet de l’âge sur l’encodage en mémoire épisodique en fonction de l’expérience recollective à la reconnaissance: étude en IRMf
François, Sarah ULg; Angel, Lucie; Salmon, Eric ULg et al

Conference (2014)

Introduction. Il est désormais communément admis que l'avancée en âge s'accompagne d'un déclin en mémoire épisodique. Plus précisément, il semblerait que, contrairement aux processus de familiarité, les ... [more ▼]

Introduction. Il est désormais communément admis que l'avancée en âge s'accompagne d'un déclin en mémoire épisodique. Plus précisément, il semblerait que, contrairement aux processus de familiarité, les processus de recollection soient particulièrement touchés (a). Chez les sujets âgés, l'encodage semble requérir une activation préfrontale bilatérale lorsqu'il est réussi, tandis que chez les sujets jeunes cette activation est latéralisée à gauche (b). Dans cette étude, nous nous sommes intéressés aux différences d'activité cérébrale entre participants jeunes et âgés lors de l'encodage en fonction du statut attribué à l'item au moment de la reconnaissance (Recollection ou Familiarité). Méthodologie. Vingt sujets jeunes (entre 19 et 29 ans) et 19 sujets âgés (entre 60 et 78 ans) ont été confrontés, lors d'un examen en IRMf, à des stimuli visuels représentant des objets à propos desquels ils devaient effectuer des jugements de taille. Lors d'une seconde phase, on présentait à nouveau aux volontaires les stimuli de la phase d'encodage ainsi que des items distracteurs. Il leur était demandé de déterminer lesquels étaient nouveaux et lesquels avaient été présentés précédemment. Parmi ces derniers, les participants effectuaient également un jugement de type Recollection- Familiarité. Les analyses statistiques ont été réalisées au moyen du logiciel SPM8, avec un plan évènementiel comparant les modifications d’activité cérébrale entre nos deux groupes de sujets lors de l’encodage (1) pour les items ayant donné lieu à un processus de recollection lors de la phase de reconnaissance par rapport à ceux associés à de la familiarité (processus de Recollection), (2) pour les items associés à de la familiarité lors de la reconnaissance par rapport à ceux non-reconnus (processus de Familiarité). Résultats. La mise en jeu de processus de recollection lors de la récupération est spécifiquement associée lors de l'encodage, chez les sujets âgés à des augmentations d'activité au niveau du gyrus frontal moyen droit, des gyri cingulaire et paracingulaire médians gauches, ainsi qu'au niveau du précuneus de manière bilatérale. Par contre, aucune activité cérébrale plus importante lors de l’encodage n’était observée dans le groupe de sujets âgés pour les items ayant induit un processus de familiarité lors de la récupération Discussion. Parmi ces régions, le précuneus semble intervenir pour favoriser des processus compensatoires permettant aux seniors d’améliorer la richesse de l’encodage, ainsi qu’il a été précédemment suggéré pour les processus de recollection lors de la récupération(c). Au contraire, les processus de familiarité, moins exigeants en ressources attentionnelles, ne semblent pas recruter de tels processus de compensation. Références (a) Bugaiska, A., Clarys, D., Jarry, C., Taconnat, L., Tapia, G., Vanneste, S., & Isingrini, M. (2007). The effect of aging in recollective experience: the processing speed and executive functioning hypothesis. Consciousness and Cognition, 16(4), 797-808. doi: 10.1016/j.concog.2006.11.007 (b) Duverne, S., Motamedinia, S., & Rugg, M. D. (2009). The relationship between aging, performance, and the neural correlates of successful memory encoding. Cerebral Cortex, 19(3), 733-744. doi: 10.1093/cercor/bhn122 (c) Angel, L., Bastin, C., Genon, S., Balteau, E., Phillips, C., Luxen, A., . . . Collette, F. (2013). Differential effects of aging on the neural correlates of recollection and familiarity. Cortex, 49(6), 1585-1597. doi: 10.1016/j.cortex.2012.10.002 [less ▲]

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See detailVisual neglect: Is there a relationship between impaired spatial working memory and re-cancellation?
Wansard, Murielle ULg; Meulemans, Thierry ULg; Gillet, Sophie ULg et al

in Experimental Brain Research (2014)

In visual search tasks, neglect patients tend to explore and repeatedly re-cancel stimuli on the ipsilesional side, as if they did not realize that they had previously examined the rightward locations ... [more ▼]

In visual search tasks, neglect patients tend to explore and repeatedly re-cancel stimuli on the ipsilesional side, as if they did not realize that they had previously examined the rightward locations favoured by their lateral bias. The aim of this study was to explore the hypothesis that a spatial working memory deficit explains these ipsilesional re-cancellation errors in neglect patients. For the first time, we evaluated spatial working memory and re-cancellation through separate and independent tasks in a group of patients with right hemisphere damage and a diagnosis of left neglect. Results showed impaired spatial working memory in neglect patients. Compared to the control group, neglect patients cancelled fewer targets and made more re-cancellations both on the left side and on the right side. The spatial working memory deficit appears to be related to re-cancellations, but only for some neglect patients. Alternative interpretations of re-exploration of space are discussed. [less ▲]

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See detailEarly neuropsychological detection of Alzheimer's disease
Bastin, Christine ULg; Salmon, Eric ULg

in European Journal of Clinical Nutrition (2014), 68

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See detailCortical and subcortical contributions to state- and strength-based perceptual judgments
Aly, Mariam; Wansard, Murielle ULg; Segovia-Román, Fermín ULg et al

in Neuropsychologia (2014), 64

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See detailFunctional connectivity and recognition of familiar faces in Alzheimer’s disease
Kurth, Sophie ULg; Bahri, Mohamed Ali ULg; Moyse, Evelyne ULg et al

in Frontiers in Human Neuroscience (2014)

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See detailThe Role of Memory Traces Quality in Directed Forgetting: A Comparison of Young and Older Participants
Collette, Fabienne ULg; Grandjean, Julien; Lorant, Caroline ULg et al

in Psychologica Belgica (2014), 54(4), 310-327

The presence of a reduced directed-forgetting (DF) effect in normal aging has been frequently observed with the item method. These results were interpreted as age-related difficulties in inhibiting the ... [more ▼]

The presence of a reduced directed-forgetting (DF) effect in normal aging has been frequently observed with the item method. These results were interpreted as age-related difficulties in inhibiting the processing of irrelevant information. However, since the performance of older adults is usually lower on items to remember, the age effect on DF abilities could also be interpreted as reflecting memory problems. Consequently, the present study aimed at investigating the influence of memory traces quality on the magnitude of the DF effects in normal aging. We predicted that increasing the quality of memory traces (by increasing presentation times at encoding) would be associated with attenuated DF effects in older participants due to the increased difficulty of inhibiting highly activated memory traces. A classical item-method DF paradigm was administered to 48 young and 48 older participants under short and long encoding conditions. Memory performance for information to memorize and to suppress was assessed with recall and recognition procedures, as well as with a Remember/Know/Guess (RKG) paradigm. The results indicated that, when memory traces are equated between groups, DF effects observed with the recall, recognition and RKG procedures are of similar amplitude in both groups (all ps>0.05). This suggests that the decreased DF effect previously observed in older adults might not actually depend on their inhibitory abilities but may rather reflect quantitative and qualitative differences in episodic memory functioning. [less ▲]

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See detailCognitive and neuroimaging evidence of impaired interaction between Self and memory in Alzheimer’s disease
Genon, Sarah ULg; Bahri, Mohamed Ali ULg; Collette, Fabienne ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2014), 51

In human cognition, self and memory processes strongly interact, as evidenced by the memory advantage for self-referential materials (Self Reference Effect (SRE) and Self Reference Recollection Effect ... [more ▼]

In human cognition, self and memory processes strongly interact, as evidenced by the memory advantage for self-referential materials (Self Reference Effect (SRE) and Self Reference Recollection Effect (SRRE)). The current study examined this interaction at the behavioural level and its neural correlates in patients with Alzheimer’s disease (AD). Healthy older controls (HC) and AD patients performed trait-adjectives judgements either for self-relevance or for other-relevance (encoding phase). In a first experiment, the encoding and subsequent yes-no recognition phases were administrated in an MRI scanner. Brain activation as measured by fMRI was examined during self-relevance judgements and anatomical images were used to search for correlation between the memory advantage for self-related items and grey matter density (GMD). In a second experiment, participants described the retrieval experience that had driven their recognition decisions (familiarity vs. recollective experience). The behavioural results revealed that the SRE and SRRE were impaired in AD patients compared to HC participants. Furthermore, verbal reports revealed that the retrieval of self-related information was preferentially associated with the retrieval of contextual details, such as source memory in the HC participants, but less so in the AD patients. Our imaging findings revealed that both groups activated the medial prefrontal cortex (MPFC) at encoding during self-relevance judgments. However, the variable and limited memory advantage for self-related information was associated with GMD in the lateral prefrontal cortex in the AD patients, a region supporting high-order processes linking self and memory. These findings suggest that even if AD patients engage MPFC during self-referential judgments, the retrieval of self-related memories is qualitatively and quantitatively impaired in relation with altered high-order processes in the lateral PFC. [less ▲]

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See detailExploration of unitization processes in episodic memory in Alzheimer's disease
Delhaye, Emma ULg; Salmon, Eric ULg; Bastin, Christine ULg

in Frontiers in Human Neuroscience (2014)

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