References of "SALMON, Eric"
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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is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors.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is characterized by the misidentification of people and by the delusional belief that the misidentified persons have been replaced by impostors, generally perceived as persecutors.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 detailBiodistribution and radiation dosimetry for the novel SV2A radiotracer [18F]UCB-H: Firstin- human study.
Bretin, Florian ULg; Bahri, Mohamed Ali ULg; BERNARD, Claire ULg et al

in Molecular Imaging & Biology (in press)

Abstract- [18F]UCB-H is a novel radiotracer with a high affinity for SV2A, a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a “first in class” antiepileptic drug with a ... [more ▼]

Abstract- [18F]UCB-H is a novel radiotracer with a high affinity for SV2A, a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a “first in class” antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [18F]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data. Dynamic whole body PET/CT imaging was performed over approximately 110 minutes on five healthy male volunteers after injection of 144.5 ± 7.1 MBq (range, 139.1 – 156.5 MBq) of [18F]UCB-H. Major organs were delineated on CT images and time-activity curves were obtained from co-registered dynamic PET emission scans. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET-activities including voiding was simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM. The effective dose to the OLINDA/EXM 70 kg standard male was 1.54E-02 ± 6.84E-04 mSv/MBq, with urinary bladder wall, gallbladder wall and the liver receiving the highest absorbed dose. The brain, the tracer’s main organ of interest, received an absorbed dose of 1.89E-02 ± 2.32E-03 mGy/MBq. This first human dosimetry study of [18F]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for USA practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose, but showed significant differences in organ absorbed doses compared to human data. [less ▲]

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See detailThe impact of ageing on episodic memory encoding: an fMRI study
François, Sarah ULg; Angel, Lucie; Salmon, Eric ULg et al

Poster (2015, May 28)

It is now commonly accepted that a decline in episodic memory is observed with ageing: while recollection processes are impaired, familiarity seems to be relatively preserved (a). Older individuals appear ... [more ▼]

It is now commonly accepted that a decline in episodic memory is observed with ageing: while recollection processes are impaired, familiarity seems to be relatively preserved (a). Older individuals appear to recruit prefrontal areas bilaterally when their encoding is successful, while in young adults this activation is found to be left-lateralized (b). In this study, we were interested in the differences between younger and older participant regarding cerebral activity during encoding depending on whether the item elicited recollection or familiarity during the recognition phase. Twenty young volunteers (aged 19 to 29 years old) and 19 older volunteers (aged 60 to 78 years old) were presented visual stimuli depicting objects. During a first fMRI session, they were asked to make a size judgement about them. Then, in a second phase, the subjects were shown the items previously encountered during the encoding phase, as well as distractors. Participants' task was to determine which one were new and which one were seen earlier. For the latter, they also performed a Remember-Know judgement. Data were analysed using SPM8, with an event design comparing modifications in cerebral activity between the two subjects groups during encoding (1) for the items leading to recollection during the recognition phase compared to those leading to familiarity, and (2) for the items associated with familiarity during the recognition phase compared to those which were not recognized. Results show that older adults display a heightened activity in the right middle frontal gyrus, medial cingulate and paracingulate left gyri as well as in the precuneus, bilaterally when they engage recollection processes. Given that activations in these areas did not correlate with performance, they could be interepreted either as dedifferentiation or as an attempt of the ageing brain to compensate for a less elaborate encoding. However, no increase of activity was associated with familiarity processes in older adults, possibly because they are less demanding regarding attentional resources. (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 [less ▲]

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See detailThe neural bases of proactive and reactive control processes in healthy aging
Manard, Marine ULg; François, Sarah ULg; SALMON, Eric ULg et al

Poster (2015, May 28)

Background. Research on cognitive control suggests an age-related decline in proactive control abilities (an anticipatory form of control) whereas reactive control (consecutive to conflict detection ... [more ▼]

Background. Research on cognitive control suggests an age-related decline in proactive control abilities (an anticipatory form of control) whereas reactive control (consecutive to conflict detection) seems to remain intact [1]. As proactive and reactive control abilities were associated to specific brain networks [2], this study investigated age-related effects on the neural substrates associated to each kind of control. Method. A modified form of the Stroop task was administered to 16 young and 16 older adults in an event-related fMRI experiment. In this version of the Stroop task, three different contexts were created: (1) a mostly congruent context (MC, inducing reactive control) with a majority of congruent items, (2) a mostly incongruent context (MI, inducing proactive control) with mainly interfering items, (3) a neutral context (MN) with mainly neutral items. Preprocessing and statistical analyses were performed with SPM8 (p<.001 uncorrected). Results. Behavioral results (p<0.05) indicated faster processing of interferent items in the MI than MC context in young participants only. With regard to neuroimaging data, the comparison of the two groups showed that the processing of interferent items in the MI context is associated to decreased activity in (mainly right-sided) frontal and temporal areas in the older group. On the contrary, in the MC context, increased activity was observed in bilateral frontal areas for older compared to younger participants. Discussion. Behavioral results confirm that older participants have difficulties with the implementation of proactive control that is associated to decreased brain activity (compared to young participants) in areas underlying Stroop performance. However, the recruitment of supplementary frontal areas we observed in the reactive control condition suggests compensation processes. So, aging seems to differentially affect the neural networks associated to the various kinds of cognitive control. [less ▲]

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See detailThe impact of ageing on episodic memory encoding: an fMRI study
François, Sarah ULg; Angel, Lucie; Salmon, Eric ULg et al

Poster (2015, May 21)

It is now commonly accepted that a decline in episodic memory is observed with ageing: while recollection processes are impaired, familiarity seems to be relatively preserved (a). Older individuals appear ... [more ▼]

It is now commonly accepted that a decline in episodic memory is observed with ageing: while recollection processes are impaired, familiarity seems to be relatively preserved (a). Older individuals appear to recruit prefrontal areas bilaterally when their encoding is successful, while in young adults this activation is found to be left-lateralized (b). In this study, we were interested in the differences between younger and older participant regarding cerebral activity during encoding depending on whether the item elicited recollection or familiarity during the recognition phase. Twenty young volunteers (aged 19 to 29 years old) and 19 older volunteers (aged 60 to 78 years old) were presented visual stimuli depicting objects. During a first fMRI session, they were asked to make a size judgement about them. Then, in a second phase, the subjects were shown the items previously encountered during the encoding phase, as well as distractors. Participants' task was to determine which one were new and which one were seen earlier. For the latter, they also performed a Remember-Know judgement. Data were analysed using SPM8, with an event design comparing modifications in cerebral activity between the two subjects groups during encoding (1) for the items leading to recollection during the recognition phase compared to those leading to familiarity, and (2) for the items associated with familiarity during the recognition phase compared to those which were not recognized. Results show that older adults display a heightened activity in the right middle frontal gyrus, medial cingulate and paracingulate left gyri as well as in the precuneus, bilaterally when they engage recollection processes. Amongst those regions, the precuneus seems to underlie compensatory processes, allowing the elderly to perform a richer encoding, as it was previously suggested for recollection processes during recall (c). However, no increase in activity was associated with familiarity processes in older adults, possibly because they are less demanding regarding attentional resources. (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 detailRetirement age and the age of onset of Alzheimer’s disease: Results from the ICTUS study
Grotz, Catherine ULg; Letenneur, Luc; Bonsang, Eric ULg et al

in PLoS ONE (2015)

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See detail[18F]UCB-H as a new PET radiotracer for Synaptic vesicle protein 2A: A first clinical trial
Bahri, Mohamed Ali ULg; Stifkens, Mathieu; Bastin, Christine ULg et al

Poster (2015, January 27)

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, e.g., by the fact that it is ... [more ▼]

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, e.g., 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. We here aimed to investigate the cerebral distribution of [18F]UCB-H, which has a high affinity with the SV2A. Dynamic PET data of the head of 4 healthy volunteers were acquired over 100 minutes after injection of 170.4 ± 24.9 MBq of GMP produced [18F]UCB-H. The arterial input function (IF) was obtained by blood sampling. The IF was also derived from the dynamic data using the correlation coefficient method. Blood data revealed a consistent amount of [18F]UCB-H in whole blood and plasma indicating a very low degree of binding of the tracer to the red blood cells. The image-derived arterial IFs were showed to be very similar to the measured ones with a peak-ratio around 0.91 and an area-under-curve ratio about 0.98. 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, 2-tissue, and Logan Plot). The three models gave similar results with both the measured and image-derived IFs. The total distribution volume of the tracer in the brain was greater than 7 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. Image-derived IF showed to be useful for quantitative studies without the need to the arterial blood sampling. SV2A modifications may consequently be assessed in neurological pathologies such as Alzheimer’s disease. [less ▲]

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See detailLe syndrome dysexécutif pour les nuls
Adam, Stéphane; SALMON, Eric ULg; GILLAIN, Sophie ULg et al

Conference (2015, January 15)

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See detailFonctionnement exécutif et attentionnel consécutif à des lésions cérébrales acquises : une analyse de cas multiples
Hogge, Michael; Salmon, Eric ULg; Collette, Fabienne ULg

in Revue de Neuropsychologie, Neurosciences Cognitives et Cliniques (2015), 7(2), 71-99

Le fonctionnement exécutif a été conceptualisé comme un ensemble de processus cognitifs de haut niveau pouvant être clairement distingués, et dont le substrat cérébral se situerait au sein des régions ... [more ▼]

Le fonctionnement exécutif a été conceptualisé comme un ensemble de processus cognitifs de haut niveau pouvant être clairement distingués, et dont le substrat cérébral se situerait au sein des régions frontales. Un certain nombre de données obtenues notamment chez des patients présentant des lésions cérébrales acquises sont toutefois venues remettre en question cette conceptualisation. Dans ce contexte, nous avons administré une large batterie d’épreuves exécutives et attentionnelles à un petit groupe de patients cérébro-lésés (N=9) afin de déterminer, au moyen d’analyses de cas multiples, l’influence de la localisation et de l’étendue des lésions, ainsi que l’influence de difficultés attentionnelles, sur la survenue d’un syndrome dysexécutif. Les analyses de profils individuels semblent indiquer qu’un mauvais transfert d’information entre régions cérébrales antérieures et postérieures serait responsable de la survenue de troubles exécutifs, et que, dans certains cas, ce soient des difficultés attentionnelles qui déterminent ces déficits. Toutefois, il se pourrait également que l’atteinte de certaines régions clés (relativement focalisées) sous-tendant des processus cognitifs impliqués dans un large éventail de tâches exécutives soit responsable de la survenue d’un dysfonctionnement exécutif massif. [less ▲]

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See detailPrevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage
Vos; VERHEY, F.; Frölich, L. et al

in Brain : A Journal of Neurology (2015), 138

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See detailRecognition of Personally Familiar Faces and Functional Connectivity in Alzheimer’s Disease
Kurth, Sophie ULg; Moyse, Evelyne ULg; Bahri, Mohamed Ali ULg et al

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2015), 67

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See detailImpairment of age estimation from faces in Alzheimer’s disease
Moyse, Evelyne ULg; Bastin, Christine ULg; Salmon, Eric ULg et al

in Journal of Alzheimer's Disease [=JAD] (2015), 45

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

in Journal of Cognitive Neuroscience (2015), 27

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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) (2014), 55(8), 1336-1341

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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