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See detailSv2a protein levels in the kainic acid epilepsy rat model during the acute phase
Serrano Navacerrada, Maria Elisa ULiege; Becker, Guillaume ULiege; Bahri, Mohamed Ali ULiege et al

in Epilepsia (2017, December), 58(Supplement S5), 1225

Introduction The Kaïnic Acid model (KA) is one of the most validated models of temporal lobe epilepsy (TLE) (Lévesque et al.,2016). Its administration induces status epilepticus (SE), characterized by an ... [more ▼]

Introduction The Kaïnic Acid model (KA) is one of the most validated models of temporal lobe epilepsy (TLE) (Lévesque et al.,2016). Its administration induces status epilepticus (SE), characterized by an extensive neuronal damage in limbic structures (Sperk et al.,1983). Post-mortem studies, such as the epilepsy model presented in (Wang et al., 2014), show a reduction of SV2A protein levels during the chronic phase, however, no data have been reported during the acute phase (0-48h after KA injection).. The present pilot study is undertaken to evaluate in vivo, with the specific radiotracer [18F]UCB-H (Bretin et al., 2015; Warnock et al., 2014), the SV2A expression 24h after a SE produced by KA administration. Methods Two Sprague-Dawley rats were scanned at two different times: baseline, and 24h after three systemic injections of 5mg/kg KA. The scanning process consisted of a first scan with microPET (Focus 120), during 1 hour, using [18F]UCB-H (41 ± 5 MBq IV tail vein). This is followed by MRI (9.4T Agilent, anatomical T2). A coregistration was performed with PMOD 3.6 software. Data were expressed as SUV and AUC were calculated for the different brain regions. Results [18F]UCB-H microPET images exhibited a small reduction (around 10%) in SV2A brain levels after KA injections compared to the baseline, marked in thalamus, hippocampus and amygdale. MRI images obtained 24h after KA injections are in accordance with previous histological studies, revealing inflammatory edema, tissue necrosis and increased ventricle volume (Sperk et al.,1983). Conclusions These preliminary results obtained in KA treated rats show that [18F]UCB-H is able to detect alterations in SV2A levels in relevant regions for epilepsy. This radiotracer emerges as a valuable tool to follow in vivo SV2A through longitudinal studies. KA model in rats deserves as a tool for the study of epilepsy, exhibiting the same features than the human disease. References [1] Lévesque et al., J Neurosci Methods, 2016 [2] Sperk et al., Neuroscience, 1983 [3] Wang et al., J Mol Neurosci., 2014 [4] Bretin et al., Molecular Imaging and Biology, 2015 [5] Warnock et al., J Nucl Med., 2014 [5] Van Nieuwenhuyse et al., Brain Research, 2015 [6] Hellier et al., Epilepsy Res., 1998 [less ▲]

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See detailIntellectual and social enrichement linked to larger hippocampal volume in healthy aging
Narbutas, Justinas ULiege; Van Egroo, Maxime ULiege; Besson, Gabriel ULiege et al

Poster (2017, November 24)

Introduction. Decreased hippocampal volume in older adults is associated with episodic memory decline and subsequent neurodegenerative diseases. According to the dynamic polygon hypothesis, strategies ... [more ▼]

Introduction. Decreased hippocampal volume in older adults is associated with episodic memory decline and subsequent neurodegenerative diseases. According to the dynamic polygon hypothesis, strategies that increase neurogenesis of the hippocampus are likely to be successsful in delaying the onset of cognitive impairment in ageing. Several modifiable factors can have a positive effect on the size of the hippocampus, one of them being cognitive reserve. However, to date, very few studies reported an impact of cognitive reserve on hippocampal volume in healthy older adults. Therefore, the main objective of our study was to explore whether cognitive reserve is linked to hippocampal volume in healthy aging. We focussed particularly on intellectual and social enrichment during lifespan, because these aspects have been linked to hippocampal volume in clinical populations. Methods. Twenty-six healthy late middle-aged participants (51-69 y.o.) underwent 3T magnetic resonance imaging. Hippocampal volume was calculated with the Automatic Segmentation of Hippocampal Subfields (ASHS) software, which uses T1-weighted and T2-weighted MRI to obtain optimal segmentation of the hippocampus and its subfields. Raw volumetric scores obtained with ASHS were controlled for age and total intracranial brain volume. Only the main hippocampal regions (CA1, CA2, CA3, dentate gyrus) were included in the analysis. Volunteers also completed a questionnaire quantifying their lifespan engagement in intellectual (i.e. reading, hobbies) and social (i.e., volunteering, social games) enrichment. More specifically, participants had to describe the frequency of each activity they have engaged in from 6 years old to the present day. Results. Pearson correlation and hierarchical linear regression analyses revealed that higher frequency of intellectual (r = 0.40; p = 0.023) and social (r = 0.44; p = 0.013) enrichment was significantly linked to larger hippocampal volume, even when controlling for age and sex. Education, another proxy of cognitive reserve, had, however, no significant association with hippocampal volume, possibly due to restricted variance in education and small sample size. Conclusion. These results suggest that in a late middle-aged population, lifespan intellectual and social enrichment is related to larger hippocampal volume. These findings could indicate that lifespan enrichment promotes hippocampal neurogenesis. Future analysis on a larger sample will distinguish the impact of early and later life enrichment on hippocampal volume and will also assess whether this relation can modulate hippocampal-related changes in episodic memory in aging population. [less ▲]

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See detailMeasuring brain synaptic vesicle protein 2A with positron emission tomography and [18F]UCB-H.
Bahri, Mohamed Ali ULiege; Plenevaux, Alain ULiege; Aerts, Joël ULiege et al

in Alzheimer’s & Dementia: Translational Research & Clinical Interventions (2017), 4(4), 481-486

Introduction: Brain distribution of synaptic vesicle protein 2Awas measured with fluorine-18 UCBH ([18F]UCB-H) and positron emission tomography (PET). Methods: Images of synaptic density were acquired in ... [more ▼]

Introduction: Brain distribution of synaptic vesicle protein 2Awas measured with fluorine-18 UCBH ([18F]UCB-H) and positron emission tomography (PET). Methods: Images of synaptic density were acquired in healthy volunteers (two young participants and two seniors). Input function was measured by arterial blood sampling (arterial input function) and derived from PET images using carotid activity (image-derived input function). Logan graphical analysis was used to estimate regional synaptic vesicle protein 2A distribution volume. Results: [18F]UCB-H uptake was ubiquitous in cortical and subcortical gray matter. Arterial input function and image-derived input function provided regional distribution volume with a high linear relationship. Discussion: The cerebral distribution of [18F]UCB-H is similar to that recently observed with carbon-11 UCB-J ([11C]UCB-J). An accurate [18F]UCB-H quantification can be performed without invasive arterial blood sampling when no suitable reference region is available, using dynamic PET carotid activity. Brain synaptic density can be studied in vivo in normal and pathological aging. [less ▲]

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See detailCognitive brain responses during circadian wake-promotion: evidence for sleep- pressure-dependent hypothalamic activations
Reichert, Carolin Franziska; Maire, Micheline; Gabel, Virginie et al

in Scientific Reports (2017), 7(1),

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See detailPharmacokinetic characterization of [18F]UCB-H PET radiopharmaceutical in the rat brain.
Becker, Guillaume ULiege; Warnier, Corentin; Serrano Navacerrada, Maria Elisa ULiege et al

in Molecular Pharmaceutics (2017), 14(8), 2719-2725

The synaptic vesicle glycoprotein 2A (SV2A), a protein essential to the proper nervous system function, is found in presynaptic vesicles. Thus, SV2A targeting, using dedicated radiotracers combined with ... [more ▼]

The synaptic vesicle glycoprotein 2A (SV2A), a protein essential to the proper nervous system function, is found in presynaptic vesicles. Thus, SV2A targeting, using dedicated radiotracers combined with positron emission tomography (PET), allows the assessment of synaptic density in the living brain. The first-in-class fluorinated SV2A specific radioligand, [18F]UCB-H, is now available at high-activity through an efficient radiosynthesis compliant with the current good manufacturing practices (cGMP). We report here a non-invasive method to quantify [18F]UCB-H binding in rat brain with microPET. Validation study in rats confirmed the need of high enantiomeric purity to target SV2A in vivo. We demonstrated the reliability of a population-based input function to quantify SV2A in preclinical microPET setting. Finally, we investigated the in vivo metabolism of [18F]UCB-H and confirmed the negligible amount of radiometabolites in the rat brain. Hence, the in vivo quantification of SV2A using [18F]UCB-H microPET seems a promising tool for the assessment of the synaptic density in the rat brain, and opens the way for longitudinal follow-up in neurodegenerative diseases rodents’ models. [less ▲]

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See detailExploration des processus de recollection et de familiarité chez des patients présentant une plainte mnésique : Une étude longitudinale
Simon, Jessica ULiege; Collette, Fabienne ULiege; Salmon, Eric ULiege et al

Poster (2017, June 01)

Les données actuelles suggèrent une altération précoce de la recollection dans les premiers stades de la maladie d’Alzheimer. Par contre, aucun consensus n’a pu être dégagé concernant l’intégrité de la ... [more ▼]

Les données actuelles suggèrent une altération précoce de la recollection dans les premiers stades de la maladie d’Alzheimer. Par contre, aucun consensus n’a pu être dégagé concernant l’intégrité de la familiarité. En effet, certaines études suggèrent une altération précoce de ce processus, alors que d’autres montrent une préservation de celle-ci. Dans ce cadre, nous avons exploré l'impact du type de format de reconnaissance et du matériel sur la recollection et la familiarité chez des patients qui se plaignent de leur mémoire. Nous avons recruté 23 participants âgés contrôles, 9 patients présentant un trouble subjectif de la mémoire (SCI) et 23 patients présentant un trouble cognitif léger (TCL). Les participants ont réalisé une tâche de reconnaissance à choix forcé à deux alternatives et une tâche de reconnaissance Oui-Non incluant des images et des mots. Ces tâches étaient suivies d’une courte évaluation neuropsychologique. Quinze participants âgés contrôles et 23 patients ont participé au suivi, incluant une évaluation neuropsychologique, dans un délai moyen de 21 mois. Nos résultats montrent qu’à l’inclusion, les patients avec TCL avaient des performances moindres en reconnaissance que les deux autres groupes, qui ne différaient pas. De même, ces patients utilisaient moins efficacement la recollection et la familiarité par rapport aux contrôles et aux SCI, qui présentaient des performances similaires. Il n’y avait aucune interaction entre le groupe et le type de format ou le matériel. Lors du suivi, cinq patients avec TCL ont retrouvé un niveau d’efficience cognitive dans la norme et ont été considérés comme des SCI car les plaintes mnésiques étaient toujours présentes. Sur la base de l'adaptation française du test de rappel libre et indicé (RLRI-16), nous avons calculé une pente de déclin mnésique pour chacun de nos patients. Nous avons observé que les indices de recollection et de familiarité étaient expliqués par les pentes de déclin calculées sur le nombre total d’items rappelés librement. Ainsi, nous avons observé un déclin de la recollection et la familiarité dans le groupe de TCL mais pas dans celui des SCI, bien que les deux groupes se plaignent de leur mémoire. En outre, l'efficacité de la familiarité pourrait prédire un déclin cognitif futur. [less ▲]

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See detailRecognition memory is associated with hippocampal volume in aging population: new evidence from brain imaging study
Narbutas, Justinas ULiege; Blanpain, Manon ULiege; Van Egroo, Maxime ULiege et al

Poster (2017, May 31)

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory ... [more ▼]

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory declines with aging and this has been associated with hippocampal dysfunction. The main objective of our study was to explore how performance on a recognition memory task designed to assess pattern separation is associated with hippocampal volume in aging population. Method. Fourteen healthy late middle-aged participants (52-69 years-old) were evaluated on a Mnemonic Similarity Task (MST). In this task, participants study pictures and then have to discriminate between targets, similar lures, and unrelated foil objects. Recognition memory (RM) is assessed as the difference between hits and false alarms to unrelated foils, while pattern separation Bias metric (BPS) is the difference between the rate of ‘‘Similar’’ responses given to the lure items minus ‘‘Similar’’ responses given to the foils. Hippocampal volume was calculated using ASHS software, which uses T1-weighted and T2-weighted MRI to obtain optimal segmentation of hippocampal subfields. Results. Correlation analysis of preliminary data revealed that RM was significantly positively associated with the volume of the left subiculum and left perirhinal area 35. BPS was positively correlated with the volume of right CA2 region, but negatively associated with the volume of right CA3 region. Discussion. In a late middle-aged population, better visual recognition memory is associated with larger volume of the left subiculum and perirhinal area 35, two regions supporting representation of objects. [less ▲]

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See detailRecognition memory is associated with hippocampal volume in aging population: new evidence from brain imaging study
Narbutas, Justinas ULiege; Blanpain, Manon ULiege; Van Egroo, Maxime ULiege et al

Poster (2017, May 19)

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory ... [more ▼]

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory declines with aging and this has been associated with hippocampal dysfunction. The main objective of our study was to explore how performance on a recognition memory task designed to assess pattern separation is associated with hippocampal volume in aging population. Method. Fourteen healthy late middle-aged participants (52-69 years-old) were evaluated on a Mnemonic Similarity Task (MST). In this task, participants study pictures and then have to discriminate between targets, similar lures, and unrelated foil objects. Recognition memory (RM) is assessed as the difference between hits and false alarms to unrelated foils, while pattern separation Bias metric (BPS) is the difference between the rate of ‘‘Similar’’ responses given to the lure items minus ‘‘Similar’’ responses given to the foils. Hippocampal volume was calculated using ASHS software, which uses T1-weighted and T2-weighted MRI to obtain optimal segmentation of hippocampal subfields. Results. Correlation analysis of preliminary data revealed that RM was significantly positively associated with the volume of the left subiculum and left perirhinal area 35. BPS was positively correlated with the volume of right CA2 region, but negatively associated with the volume of right CA3 region. Discussion. In a late middle-aged population, better visual recognition memory is associated with larger volume of the left subiculum and perirhinal area 35, two regions supporting representation of objects. [less ▲]

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See detailRecollection versus familiarité dans le vieillissement normal et pathologique : Impact du format du test
Simon, Jessica ULiege; Gilsoul, Jessica ULiege; SALMON, Eric ULiege et al

Poster (2017, May 19)

If familiarity is better preserved than recollection in aging and in the early stage of Alzheimer's disease (Koen & Yonelinas, 2014), the experimental conditions promoting its use should be beneficial to ... [more ▼]

If familiarity is better preserved than recollection in aging and in the early stage of Alzheimer's disease (Koen & Yonelinas, 2014), the experimental conditions promoting its use should be beneficial to these populations. One condition influencing the relative contribution of recollection and familiarity during recognition is the format of the test. The aim of this study was to investigate the impact of test format on recollection and familiarity in normal aging and in MCI in two tasks where the level of performance is equalized. Seventy young participants, 70 younger-old (55-69 years old), 69 older-old (70-85 years old), and 13 MCIs were presented with forced-choice and yes/no visual recognition memory tasks with the Remember/Know/ Guess paradigm. Young participants had better recognition memory performance than younger-old, who performed better than older-old and MCIs. Recollection and familiarity declined progressively in healthy aging. In MCI, recollection was more affected than familiarity, but patients demonstrated a more liberal use of familiarity. Finally, test format did not influence strongly the results. Young people used recollection more often in the forced-choice task compared to the yes/no task. [less ▲]

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See detailExploration des processus de recollection et de familiarité chez des patients présentant une plainte mnésique : une étude longitudinale
Simon, Jessica ULiege; Collette, Fabienne ULiege; SALMON, Eric ULiege et al

Poster (2017, May 19)

Recollection refers to recall of details about past events, and familiarity is a feeling of oldness. In this study, we tested how recollection and familiarity are affected in patients with memory ... [more ▼]

Recollection refers to recall of details about past events, and familiarity is a feeling of oldness. In this study, we tested how recollection and familiarity are affected in patients with memory complaints compared to normal aging. We recruited 23 healthy older participants, 9 patients with subjective memory impairment (SCI) and 23 patients with mild cognitive impairment (MCI). Participants performed one 2-alternative forced-choice and one Yes-No recognition memory task including pictures and words, followed by a short neuropsychological evaluation. Fifteen healthy participants and 23 patients (9 SCI and 14 MCI) took part in a neuropsychological follow-up after a mean delay of 21 months. At inclusion, MCI patients had poorer performance in recognition than the other groups, which did not differ. MCI patients had worse performance regarding familiarity and recollection indexes compared to healthy controls and SCI, who exhibit similar performance. There was no interaction between groups and format or material. During the follow-up evaluation, five MCI returned to a normal level of efficiency and were considered as SCI. Based on the French adaptation of the free and cued selective reminding test (RLRI-16), we calculated cognitive decline curves in our patients. We observed that recollection and familiarity indexes were explained by the decline curves calculated on the number of freely recalled items. So, recollection and familiarity were used less efficiently in MCI than SCI although both groups complained about their memory. [less ▲]

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See detailRecollection versus familiarity in normal aging and in mild cognitive impairment: Impact of test format
Simon, Jessica ULiege; Gilsoul, Jessica ULiege; SALMON, Eric ULiege et al

Poster (2017, March 24)

If familiarity is better preserved than recollection in aging and in the early stage of Alzheimer's disease (Koen & Yonelinas, 2014), the experimental conditions promoting its use should be beneficial to ... [more ▼]

If familiarity is better preserved than recollection in aging and in the early stage of Alzheimer's disease (Koen & Yonelinas, 2014), the experimental conditions promoting its use should be beneficial to these populations. One condition influencing the relative contribution of recollection and familiarity during recognition is the format of the test. The aim of this study was to investigate the impact of test format on recollection and familiarity in normal aging and in MCI in two tasks where the level of performance is equalized. Seventy young participants, 70 younger-old (55-69 years old), 69 older-old (70-85 years old), and 13 MCIs were presented with forced-choice and yes/no visual recognition memory tasks with the Remember/Know/ Guess paradigm. Young participants had better recognition memory performance than younger-old, who performed better than older-old and MCIs. Recollection and familiarity declined progressively in healthy aging. In MCI, recollection was more affected than familiarity, but patients demonstrated a more liberal use of familiarity. Finally, test format did not influence strongly the results. Young people used recollection more often in the forced-choice task compared to the yes/no task. [less ▲]

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See detailAnosognosia for behavioral disorder is related to confidence for false self-related memories in Alzheimer’s disease
Mélon, Marlène; Collette, Fabienne ULiege; Salmon, Eric ULiege et al

Poster (2017, March 24)

Impaired self-awareness (i.e. anosognosia) and altered metacognitive monitoring in memory tasks have both been evidenced in AD. Furthermore, cognitive studies showed disrupted interaction between self and ... [more ▼]

Impaired self-awareness (i.e. anosognosia) and altered metacognitive monitoring in memory tasks have both been evidenced in AD. Furthermore, cognitive studies showed disrupted interaction between self and memory cognitive systems in AD, reducing cognitive advantages of self-related memories (i.e. decreasing self reference effect, SRE) in these patients. However, how anosognosia relates to impaired metacognitive monitoring in AD, particularly for self-related memories, is still an open question. To investigate this question, an ecological memory task based on face-name associations was administrated to 20 healthy older controls (HC) and 20 mild AD patients. The influence of self-reference at encoding was assessed on subsequent name recall and recollective experience, as well as on predictive (feeling-of-knowing, FOK) and postretrieval (judgments-of-confidence, JOC) metacognitive judgments on name recognition in all participants. Furthermore relationships between metacognitive outcomes and awareness of daily cognitive and behavioral impairment was examined in AD. Altered SRE was evidenced in name recall and recollective experience in AD. Patients also showed impaired FOK and JOC, as well as lower awareness of their daily functioning impairment (anosognosia). Nevertheless, differential effect of self on metacognitive judgment in AD and HC was only observed on JOC for false memories. Importantly, anosognosia for behavioral disorders was related to post-retrieval confidence for false recognition of self-related items in AD patients. Thus, anosognosia concerning behavioral disorder and altered post-retrieval monitoring of self-related memories appear to be related in AD. We hypothesized that impaired monitoring of personal false memories may lead AD patients to rely on distorted recent reality when providing judgment about their everyday behavioral functioning. [less ▲]

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See detailRelating pessimistic memory predictions to Alzheimer’s disease brain structure
Genon, Sarah ULiege; Simon, Jessica ULiege; Bahri, Mohamed Ali ULiege et al

Poster (2017, March 23)

Patients with Alzheimer’s disease (AD) show impairment of episodic memory and related metacognitive processes. The present study examined subjective metacognitive judgments preceding objective memory ... [more ▼]

Patients with Alzheimer’s disease (AD) show impairment of episodic memory and related metacognitive processes. The present study examined subjective metacognitive judgments preceding objective memory retrieval and investigated the neural correlates of pessimistic predictions for successfully retrieved memories in AD patients. AD patients and healthy older participants provided predictive judgements on their recognition performance before retrieval of famous (semantic) and recently learned (episodic) names. Correlations between grey matter volume (GMV) in T1 images and behavioural scores were examined with multivariate (PLS) and univariate (GLM) analyses in AD patients. AD patients showed a significant proportion of successful name recognition preceded by pessimistic prediction (Prediction_low_hits) in episodic memory. PLS revealed that behavioural pattern in AD patients was related with a mainly right lateralized pattern of GMV decrease including medial temporal lobe and posterior cingulate cortex, but also right ventrolateral prefrontal cortex (VLPFC). GLM further confirmed that pessimistic prediction negatively correlated with GMV in VLPFC. Thus, impaired monitoring processes (possibly influenced by inaccurate beliefs) allowing inferences about one’s own memory performance are primarily related to decrease GMV in VLPFC in AD patients. [less ▲]

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See detailRecognition memory is associated with hippocampal volume in aging population: new evidence from brain imaging study
Narbutas, Justinas ULiege; Blanpain, Manon ULiege; Van Egroo, Maxime ULiege et al

Poster (2017, March 23)

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory ... [more ▼]

Introduction. The hippocampus is crucial for episodic memory, especially for recollection and pattern separation (i.e., the ability to store similar episodes as distinct memory traces). Episodic memory declines with aging and this has been associated with hippocampal dysfunction. The main objective of our study was to explore how performance on a recognition memory task designed to assess pattern separation is associated with hippocampal volume in aging population. Methods. Fourteen healthy late middle-aged participants (52-69 years-old) were evaluated on a Mnemonic Similarity Task (MST). In this task, participants study pictures and then have to discriminate between targets, similar lures, and unrelated foil objects. Recognition memory (RM) is assessed as the difference between hits and false alarms to unrelated foils, while pattern separation Bias metric (BPS) is the difference between the rate of ‘‘Similar’’ responses given to the lure items minus ‘‘Similar’’ responses given to the foils. Hippocampal volume was calculated using ASHS software, which uses T1-weighted and T2-weighted MRI to obtain optimal segmentation of hippocampal subfields. Results. Correlation analysis of preliminary data revealed that RM was significantly positively associated with the volume of the left subiculum and left perirhinal area 35, while there were no significant correlations in the right hemisphere. BPS was positively correlated with the volume of right CA2 region, but negatively associated with the volume of right CA3 region, what is more contradictory according to the current literature. No significant link was found between BPS and the volume of hippocampal subfields in the left hemisphere. Conclusion. In a middle-aged population, better visual recognition memory is associated with larger volume of the left subiculum and perirhinal area 35, two regions supporting representation of objects [less ▲]

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See detailNeural correlates of subsequent recollection and familiarity in ageing
François, Sarah ULiege; Angel, Lucie; Salmon, Eric ULiege et al

Poster (2017, March)

It is now commonly accepted that, in ageing, recollection processes are impaired and familiarity seems to be relatively preserved. In this study, we were interested in the differences between younger and ... [more ▼]

It is now commonly accepted that, in ageing, recollection processes are impaired and familiarity seems to be relatively preserved. In this study, we were interested in the differences between younger and older participants regarding cerebral activity during encoding depending on whether the item later elicited recollection or familiarity. Twenty young volunteers and 19 older volunteers were presented visual stimuli depicting objects. After a first fMRI session in which the items were encoded, they underwent a recognition memory task in which they judged whether items were Remembered, Familiar or New. Data were analysed using SPM8, with an event-related design comparing modifications in cerebral activity between the two subjects groups during encoding (1) for the items leading to recollection compared to those leading to familiarity, and (2) for the items associated with familiarity compared to those which were not recognized. Results showed that older adults displayed a heightened activity in regions of the default-mode network for subsequent recollection. As it does not appear to be deleterious, it could stem from a more frequent use of self-referential appraisal as an encoding strategy in older adults. Furthermore, they show supplementary contralateral activations in frontal and temporal regions, which could be indicative of dedifferentiation or attempted compensation. To conclude, it appears that despite relying less on elaborative encoding, older adults seem to be able to perform recollection using qualitatively different strategies than young adults. [less ▲]

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See detailNoninvasive quantification of [18F]UCB-H binding using microPET and population-based input function.
Becker, Guillaume ULiege; Warnier, C; Serrano Navacerrada, Maria Elisa ULiege et al

Poster (2017, February 19)

Introduction: [18F]UCB-H is a validated radiotracer with a high affinity for the synaptic vesicle glycoprotein 2A (SV2A), known as the binding site of the antiepileptic drug levetiracetam [1, 2]. Due to ... [more ▼]

Introduction: [18F]UCB-H is a validated radiotracer with a high affinity for the synaptic vesicle glycoprotein 2A (SV2A), known as the binding site of the antiepileptic drug levetiracetam [1, 2]. Due to the absence of reference region, the major drawback of SV2A microPET imaging in the living rat brain is the invasiveness and the complexity of the arterial input function measurement needed for a full quantification. We provide here evaluation of a population-based input function (PBIF) to estimate input function of [18F]UCB-H. Methods: Standard arterial input functions were measured with an arteriovenous shunt and a β-microprobe system from eight anesthetized Sprague-Dawley (SD) rats, as previously described [2]. The distribution volume (Vt) for [18F]UCB-H was calculated with Logan graphic analysis. After normalization, all individual AIFs were averaged to provide the PBIF, and the Logan graphical analysis was computed on each individual rat using the PBIF instead of individual AIF. Correlations analyses were computed between Vt obtained with each methods (individual AIF vs PBIF). Finally, another cohort of five SD rats was scanned with [18F]UCB-H, and Vt were computed using the PBIF and Logan analysis. Single blood samples were harvested at 15 min after radiotracer injection, just to ensure the consistency of the metabolic parent fraction. Results: The Vt computed with individual AIFs were higly consistent with previously reported values, so are the Vt computed with the PBIF [2]. Individual AIFs Vt and PBIF Vt are highly correlated through all brain areas for the height subjects (r2 =0.9). Coefficients of variance are slightly higher with the PBIF method compare to the individual AIF method (14 % and 9 % respectively for the whole brain). Finally, Vt measurement in the second cohort were consistent with previously reported values, and the metabolization profile matched the parent fraction described by Warnock and coll. [2]. Conclusions: The present study described a method for the noninvasive estimation of the AIF using a PBIF, carrying a potential that might substitute for conventional invasive, indivi- dual AIF measurement. We propose that this method can provide a reasonable solution for longitudinal quantitative [18F]UCB-H microPET studies. [less ▲]

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See detailEvaluating the specificity of [18F] UCB-H for the isoform SV2A, compared with isoforms SV2B and SV2C
Serrano Navacerrada, Maria Elisa ULiege; Becker, Guillaume ULiege; Bahri, Mohamed Ali ULiege et al

Poster (2017, February 01)

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important in normal and pathological process, like the ... [more ▼]

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important in normal and pathological process, like the epilepsy (1, 2). [18F]UCB-H was developed like a tool to study the role of this isoform with neuroimaging techniques (3, 4). The objective of this study was to evaluate its specificity to this isoform comparing with the others, through a competition assay in rats with ex-vivo autoradiography and mPET imaging. Methods: Forty male Sprague-Dawley were used in ex-vivo autoradiography experiments (N=20) and in microPET imaging (N=20). Animals were pre-treated 30 minutes before the injection of [18F]UCB-H with a dose IP either of vehicle, Keppra (SV2A ligand), UCB068 (SV2B ligand) or UCB054 (SV2C ligand). Ex-vivo autoradiography was carried out 5 minutes after radiotracer injection while mPET images were acquiring with a dynamic scanner of 1 hour. Data were expressed in Standard Uptake Value and then, the area under the curve was calculated for the total process. Results: In ex-vivo autoradiography, ANOVA of two-ways showed statistical significant differences in brain uptake of [18F]UCB-H among the groups pretreated with Keppra or the ligand for SV2B and the control group. Regarding mPET data, statistical significant differences were found between the group injected with keppra and the rest of groups. Conclusion: Even if a considerable affinity between the ligands UCB068 and UCB054, and the receptor for the isoform SV2A exists, it is only detected during the first 5 minutes (ex-vivo technique), being certainly due to a nonspecific binding. This binding is not strong enough to show a direct competition with the radiotracer during a mPET acquisition. These results allow us to conclude that [18F]UCB-H is a suitable radiotracer for the imaging of the isoform SV2A in vivo, allowing us the clinical study about the molecular base of a disease with a high population impact, like the epilepsy. [less ▲]

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See detailDecreased Synaptic Density in Early Alzheimer’s Disease Assessed with [18F]UCB-H-PET
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