References of "SALMON, Eric"
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See detailThe neural basis of temporal order processing in past and future thought
D'Argembeau, Arnaud ULg; Jeunehomme, Olivier; Majerus, Steve ULg et al

in Journal of Cognitive Neuroscience (in press)

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See detailEvaluation of [18F]UCB-H as a novel PET tracer for synaptic vesicle protein 2A in the brain.
Warnock, Geoffrey; Aerts, Joël ULg; Bahri, Mohamed Ali ULg et al

in Journal of Nuclear Medicine (The) (in press)

Synaptic vesicle 2 (SV2) proteins are critical to proper nervous system function and are involved in vesicle trafficking. The SV2A isoform has been identified as the binding site of the antiepileptic ... [more ▼]

Synaptic vesicle 2 (SV2) proteins are critical to proper nervous system function and are involved in vesicle trafficking. The SV2A isoform has been identified as the binding site of the antiepileptic levetiracetam (LEV), making it an interesting therapeutic target for epilepsy. [18F]UCB-H is a novel PET imaging agent with a nanomolar affinity for human SV2A. Methods: preclinical PET studies were carried out in isoflurane anesthetized rats. Arterial input function was measured using an arteriovenous shunt and beta microprobe system. [18F]UCB-H was injected IV (140 ± 20 MBq bolus). Results: brain uptake of [18F]UCB-H was high, matching the expected homogeneous distribution of SV2A. The distribution volume (Vt) for [18F]UCB-H was calculated using Logan’s graphical analysis and the effect of LEV pretreatment on Vt measured. In control animals the mean whole-brain Vt was 9.76 ± 0.52 ml/cm3 (mean ± SD, n=4, test-retest), and the mean reproducibility in test-retest studies was 10.4 ± 6.5 %. Uptake of [18F]UCB-H was dose-dependently blocked by pretreatment with LEV (0.1 - 100 mg/kg IV). Conclusion: our results indicate that [18F]UCB-H is a suitable radiotracer for the imaging of SV2A in vivo. This is the first PET tracer for in vivo quantification of SV2A. The necessary steps for implementation of [18F]UCB-H production under GMP conditions and first in human studies are planned. [less ▲]

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See detailBrain metabolic dysfunction in Capgras delusion during Alzheimer’s disease: a positron emission tomography study
Jedidi, Haroun ULg; Daury, Noémy; Rémi, Capa et al

in American Journal of Alzheimer's Disease & Other Dementias (in press)

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since ... [more ▼]

Capgras delusion is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors. Since little is known regarding the neural correlates of Capgras syndrome, the cerebral metabolic pattern of a patient with probable Alzheimer’s disease (AD) and Capgras syndrome was compared with those of 24 healthy elderly subjects and 26 AD patients without delusional syndrome. Compared to the healthy and AD groups, the patient had significant hypometabolism in frontal and posterior midline structures. In light of current neural models of face perception, our patient’s Capgras syndrome may be related to impaired recognition of a familiar face, subserved by the posterior cingulate/precuneus cortex, and impaired reflection about personally relevant knowledge related to a face, subserved by the dorsomedial prefrontal cortex. [less ▲]

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See detail[18F]UCB-H AS A NEW PET RADIOTRACER FOR SYNAPTIC VESICLE PROTEIN 2A
Bahri, Mohamed Ali ULg; Bastin, Christine ULg; Aerts, Joël ULg et al

Poster (2014, June 06)

Synaptic vesicle protein 2A (SV2A) is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown ... [more ▼]

Synaptic vesicle protein 2A (SV2A) is widely distributed in the brain and has been demonstrated to be involved in vesicle trafficking. The critical role of SV2A in proper nervous system function is shown, for example, by the fact that it is a binding site and the primary mechanism of levetiracetam. Levetiracetam is an antiepileptic drug which has recently been suggested to reduce synaptic deficits in a mouse model for Alzheimer’s disease and to improve cognition in patients with amnestic mild cognitive impairment. We here aimed to investigate the cerebral distribution of [18F]UCB-H, a fluorine-18 radiolabelled PET imaging tracer, which has a high affinity with the SV2A. [18F]UCB-H was radiosynthesized under GMP conditions. Dynamic PET data of the head of four healthy volunteers were acquired over 100 minutes after injection of 170.4 ± 24.9 MBq of [18F]UCB-H. The arterial input function was obtained by blood sampling during the dynamic PET acquisition. The analysis of the blood data reveled a consistent amount of [18F]UCB-H in whole blood and plasma which indicates a very low degree of binding of the tracer to the red blood cells. The unchanged fraction of [18F]UCB-H in plasma showed 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 decreased to about 50% at 10 min post injection. The [18F]UCB-H PET data showed a high and rapid uptake in the grey matter structures, matching the known ubiquitous distribution of the 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 the [18F]UCB-H in the brain greater than 7 mL/cm3 and a specific distribution volume around 3 mL/cm3. Our results suggest that [18F]UCB-H is a good candidate as radiotracer for brain SV2A proteins and could be used for human studies. In the future, SV2A modifications might be assessed in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailExecutive function and grey matter atrophy in healthy aging: A voxel-based morphometry analysis
Manard, Marine ULg; Bahri, Mohamed Ali ULg; Salmon, Eric ULg et al

Poster (2014, June)

Introduction Executive functioning is one of the cognitive domain that declines in healthy aging (Salthouse, Atkinson, & Berish, 2003). In addition, neuroimaging studies pointed out diverse ... [more ▼]

Introduction Executive functioning is one of the cognitive domain that declines in healthy aging (Salthouse, Atkinson, & Berish, 2003). In addition, neuroimaging studies pointed out diverse neurobiological modifications associated to normal aging, such as reduced grey and white matter volumes and cortical thickness (Raz & Rodrigue; 2006). In that context, Voxel Based Morphometry (VBM; Ashburner & Friston, 2000) and Partial Least Square (PLS; McIntoch at al., 1996, 2004) were used to investigate the effect of grey matter atrophy on executive abilities in normal aging. Methods Thirty six young (age range: 18-30) and 43 healthy older (age range: 60-78) adults were included in this study. Executive functioning was assessed by inhibition, updating and shifting tasks (Miyake et al., 2000), and a composite score for general executive ability was created. Structural high resolution T1-weighted images were acquired with a 3T head-only scanner using a standard transmit-receive quadrature head coil (Siemens, Allegra, Erlangen, Germany). The structural images were segmented using VBM8 toolbox, normalized to the MNI stereotaxic space and the resulting grey matter volume images were smoothed (Gaussian kernel: FWHM 8mm). PLS analyses were performed to determine regional grey matter volume differences between young and older adults, and next to identify the regional grey matter volumes specifically associated to executive performance in older participants (p<0.001). PLS is a validated multivariate approach that robustly identifies whole brain activity patterns correlated with behavioral data or experimental design (i.e., scores, conditions or tasks). Results Behavioral data showed a significant age-related decline in executive functioning (t=-5.43; p<.001). MRI analyses showed that significant age-related grey matter volume decrease was mostly observed across a large network including frontal, parietal, and temporal regions. Moreover significant positive correlations between the executive score and the grey matter volumes in older participants were found in a subset of these cortical areas: the inferior, middle and superior frontal cortex, the pre and postcentral gyri, the anterior and middle cingulate cortex, the inferior and superior parietal regions, the retrosplenial cortex, and finally, the inferior, middle and superior temporal regions. Discussion This study first replicated that executive abilities decline with age (Salthouse et al., 2003). This age-related executive decline is related to specific cerebral regions within a large fronto-temporo-parietal network sensitive to age. Interestingly, the areas whose atrophy is linked to executive abilities are quite similar to those evidenced in functional neuroimaging studies in young participants (see Collette & Van der Linden, 2002; Collette, Hogge, Salmon, & Van der Linden, 2006 for reviews). Therefore, using PLS multivariate analyses, we demonstrated that executive changes in normal aging are not dependent on atrophy in frontal areas only but rather comes from a grey matter volume decrease in a large antero-posterior brain network. [less ▲]

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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 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 detailLes effets du vieillissement normal et pathologique sur la cognition
Collette, Fabienne ULg; Salmon, Eric ULg

in Revue Médicale de Liège (2014), 69(5-6), 265-269

Des troubles cognitifs touchant principalement le fonctionnement exécutif et mnésique sont observés lors du vieillissement normal et de la maladie d’Alzheimer, et sont associés à des changements au niveau ... [more ▼]

Des troubles cognitifs touchant principalement le fonctionnement exécutif et mnésique sont observés lors du vieillissement normal et de la maladie d’Alzheimer, et sont associés à des changements au niveau de l’activité cérébrale. Il apparait toutefois que différents facteurs sont susceptibles de retarder la survenue des troubles cognitifs, tels que la stimulation mentale ou la pratique d’une activité physique. De même, les prises en charge cognitives permettent d’améliorer le fonctionnement au quotidien des patients présentant une maladie d’Alzheimer (MA). Identifier les facteurs et techniques qui contribuent à maintenir une vitalité cognitive et/ou à contrer les effets de la MA permettront d’optimiser la qualité de vie des seniors. [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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See detailMetabolic cerebral correlates of conjunctive and relational memory in Alzheimer's disease
Bastin, Christine ULg; Bahri, Mohamed Ali ULg; Collette, Fabienne ULg et al

Poster (2014)

Introduction. Memory deficits are the clinical hallmark of typical Alzheimer’s disease. The precise nature of these deficits however remains to be fully characterized. In this study, we investigated ... [more ▼]

Introduction. Memory deficits are the clinical hallmark of typical Alzheimer’s disease. The precise nature of these deficits however remains to be fully characterized. In this study, we investigated binding in long-term episodic memory. Relational binding processes in memory create an associative link between independent items or between items and context into episodic memories (Cohen et al., 1999). An alternative process, conjunctive binding, allows associations to be encoded as a united representation of features into a single entity (O'Reilly and Rudy, 2001; Mayes et al., 2007). The current study (1) assessed whether Alzheimer’s disease disrupt both conjunctive and relational memory, and (2) related patients’ memory performance to cerebral metabolism. Methods. Thirty patients with mild Alzheimer’s disease and 24 healthy older adults performed a source memory task where items were associated to a background color (Diana et al., 2008, 2010). In one condition, relational binding was promoted by the instruction to associate the item with another object of the same color as the background. In the other condition, color had to be integrated as an item feature (conjunctive binding). Patients’ brain metabolic activity at rest (FDG-PET) was analysed with spatio-temporal Partial Least Squares (McIntosh et al., 1996) in order to assess the relation of behavioral performance and activity in functional cerebral networks. Results. Alzheimer’s disease patients had an impaired capacity to remember item-color associations, with deficits in both relational and conjunctive memory. However, performance in the two kinds of associative memory varied independently across patients. Partial least square analyses revealed a significant pattern of metabolic activity that correlated specifically with each condition (accounting for 76.48 % of the covariance in the data; p< .05). More specifically, poor conjunctive memory was related to hypometabolism in an anterior temporal-posterior fusiform brain network, whereas relational memory correlated with metabolism in regions of the default mode network. Conclusions. These findings support the hypothesis of distinct neural systems specialized in different types of associative memory and point to heterogeneous profiles of memory alteration in Alzheimer’s disease as a function of damage to the respective neural networks. [less ▲]

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See detailBrains creating stories of selves: the neural basis of autobiographical reasoning.
D'Argembeau, Arnaud ULg; Cassol, Helena; Phillips, Christophe ULg et al

in Social Cognitive and Affective Neuroscience (2014), 9

Personal identity critically depends on the creation of stories about the self and one's life. The present study investigates the neural substrates of autobiographical reasoning, a process central to the ... [more ▼]

Personal identity critically depends on the creation of stories about the self and one's life. The present study investigates the neural substrates of autobiographical reasoning, a process central to the construction of such narratives. During fMRI scanning, participants approached a set of personally significant memories in two different ways: on some trials, they remembered the concrete content of the events (autobiographical remembering), whereas on other trials they reflected on the broader meaning and implications of their memories (autobiographical reasoning). Relative to remembering, autobiographical reasoning recruited a left-lateralized network involved in conceptual processing (including the dorsal medial prefrontal cortex (MPFC), inferior frontal gyrus, middle temporal gyrus, and angular gyrus). The ventral MPFC-an area that may function to generate personal/affective meaning-was not consistently engaged during autobiographical reasoning across participants but, interestingly, the activity of this region was modulated by individual differences in interest and willingness to engage in self-reflection. These findings support the notion that autobiographical reasoning and the construction of personal narratives go beyond mere remembering in that they require deriving meaning and value from past experiences. [less ▲]

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See detailLes modifications du fonctionnement exécutif dans le vieillissement normal
Collette, Fabienne ULg; Salmon, Eric ULg

in Psychologie Française (2014), 59(1), 41-58

Il est maintenu bien reconnu que le vieillissement cognitif est associé à une diminution des capacités exécutives. Toutefois, si des déficits sont effectivement observés au sein des différentes fonctions ... [more ▼]

Il est maintenu bien reconnu que le vieillissement cognitif est associé à une diminution des capacités exécutives. Toutefois, si des déficits sont effectivement observés au sein des différentes fonctions, des dissociations entre performances préservées/altérées ont également été observées au sein de chacune. Dans cette revue de question, nous détaillerons les effets du vieillissement dans les fonctions de mise à jour, flexibilité, inhibition et coordination de tâches doubles, ainsi que les modifications au sein des réseaux cérébraux associés à ces processus. Nous discuterons également l'influence des capacités attentionnelles, des ressources en mémoire de travail et de certaines caractéristiques génétiques sur ces modifications. [less ▲]

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See detailA Partial Least Squares Analysis of the self reference effect in Alzheimer's disease: A reply to Irish
Genon, Sarah ULg; Bastin, Christine ULg; Angel, Lucie et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2014), 54

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