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See detailIN VIVO STUDY OF THE SV2A PROTEIN IN THE KAINIC ACID EPILEPSY RAT MODEL
Serrano Navacerrada, Maria Elisa ULiege; Becker, Guillaume ULiege; Bahri, Mohamed Ali ULiege et al

Poster (2017)

Introduction Epilepsy is one of the commonest neurological disorders [1]. Antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed to ... [more ▼]

Introduction Epilepsy is one of the commonest neurological disorders [1]. Antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed to study in vivo SV2A brain proteins [3, 4]. The present pilot study was undertaken to evaluate for the first time in vivo in rats SV2A expression in the Kaïnic Acid (KA) epilepsy model [5]. Although this model is well studied in mice, few reports were devoted to rats. Imaging-wise, rats are very interesting thanks to a bigger brain size (reduction of the partial volume effect). Methods Three male Sprague-Dawley were used, one injected with saline and two with multiple KA injections (3 x 5mg/kg) [6]. 75 days later, when spontaneous seizures started to appear, microPET (Focus 120 ) was performed under isoflurane anesthesia (2.5-3 % in air) for 1 hour with [18F]UCB-H (41 ± 5 MBq IV tail vein) followed by MRI (9.4T Agilent, anatomical T2). Coregistration was done with PMOD 3.6 software. Data were expressed as SUV and areas under the curve were calculated for the different regions. Results [18F]UCB-H microPET images showed an important reduction (20-30%) for SV2A after KA injections mainly localized in amygdala, hippocampus, lateral parietal association cortex and cingulate cortex. The rest of the brain was globally unchanged. MRI revealed atrophy and inflammation in amygdala and hippocampus. Conclusions These preliminary results obtained in KA treated rats showed that [18F]UCB-H was able to detect important modifications for SV2A in relevant regions for epilepsy and appears as a valuable tool to follow in vivo SV2A through longitudinal studies. KA model in rats deserves for further development and validation as a tool for the study of epilepsy. [less ▲]

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See detailIN VIVO STUDY OF THE SV2A PROTEIN IN AN EPILEPTIC RAT MODEL
Serrano Navacerrada, Maria Elisa ULiege; Becker, Guillaume ULiege; Bahri, Mohamed Ali ULiege et al

Poster (2017)

Introduction Epilepsy is one of the commonest neurological disorders, affecting more than 60 million people worldwide [1]. New and effective antiepileptic drugs mainly target the SV2A protein [2] but its ... [more ▼]

Introduction Epilepsy is one of the commonest neurological disorders, affecting more than 60 million people worldwide [1]. New and effective antiepileptic drugs mainly target the SV2A protein [2] but its actual role is still largely unknown. [18F]UCB-H was developed as a tool to study in vivo the brain expression of this isoform [3, 4]. Due to the fact that only post-mortem studies were reported so far [5] the present pilot study was undertaken in order to evaluate for the first time in vivo in rats the SV2A expression in the validated Kaïnic Acid (KA) epilepsy model [6]. Methods Three male Sprague-Dawley were used, one injected with saline (Sham) and two with multiple KA systemic injections (5mg/kg x 3) [9]. SV2A brain levels were estimated at day 75, when spontaneous seizures started to appear. Animals were anesthetized (2.5 to 3 % isoflurane), and scanned for 1 hour with [18F]UCB-H (41 ± 5 MBq IV tail vein) in a Focus 120 microPET system and with MRI (9.4T Agilent, anatomical T2). Coregistration was done with PMOD 3.6 software. Data were expressed in SUV and areas under the curve were calculated for the different regions. Results [18F]UCB-H microPET images showed an important reduction (20-30%) for SV2A after KA injections mainly localized in amygdala, hippocampus, lateral parietal association cortex and cingulate cortex. The rest of the brain was globally unchanged. MRI revealed atrophy and inflammation in amygdala and hippocampus. Conclusions These preliminary results in KA treated rats presenting spontaneous seizures showed that [18F]UCB-H microPET was able to detect important reductions for the SV2A proteins in relevant regions for epilepsy [5]. Accordingly to this, we can infer that the KA model in rats deserves for further development and validation as a tool for the study of epilepsy. [18F]UCB-H appears as a valuable tool to follow in vivo SV2A proteins through longitudinal protocols and in turn to better understand its actual role in epilepsy. References/acknowledgements This work was funded by University of Liège, F.R.S.-FNRS, Walloon Region and UCB Pharma. Alain Plenevaux is research director from F.R.S.-FNRS. [1] Alexopoulos, Epileptology, 2004 [2] Hamann et al., Eur J Pharmacol, 2008 [3] Bretin et al., Molecular Imaging and Biology, 2015 [4] Warnock et al., J Nucl Med., 2014 [5] Wang et al., J Mol Neurosci., 2014 [6] Hellier et al., Epilepsy Res., 1998 [less ▲]

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See detail[18F]UCB-H RADIOTRACER AS A TOOL TO UNDERSTAND THE ROLE OF THE SV2A PROTEIN
Serrano Navacerrada, Maria Elisa ULiege; Becker, Guillaume ULiege; Bahri, Mohamed Ali ULiege et al

Poster (2017)

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important both in normal as in pathological process (1, 2 ... [more ▼]

Background: SV2A is the most studied isoform of the Synaptic Vesicle 2 proteins, which are involved in the synaptic vesicle trafficking, being important both in normal as in pathological process (1, 2). Until now, only one study in vivo has been reported, showing a reduction of SV2A levels in the epilepsy (3). [18F]UCB-H was developed like a current tool to study the role of SV2A with in vivo techniques (4, 5), and as a tool in clinical investigations. The objective of this research was to evaluate the radiotracer 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. Standard Uptake Value (SUV) and Distribution Volume (VT) were calculated and the correlation between both parameters was determined. 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. Pearson Correlation between SUV and VT was strong, with a value of 0.955. 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. 1) Van Vliet et al., 2009. Epilepsia 2) Crèvecœur et al., 2013. BMC Neurosci. 3) Finnema et al., 2016; Sci Transl Med. 4) Bretin et al., 2013.EJNMMI Res 5) Bretin et al., 2015.Mol Imaging Biol [less ▲]

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See detailThe impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: an EADC study
Bosco, P.; Redolfi, A.; Bocchetta, M. et al

in Alzheimer's & Dementia : The Journal of the Alzheimer's Association (2017)

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See detailAnosognosie et monitoring des souvenirs associés au « soi » dans la Maladie d’Alzheimer
Genon, Sarah ULiege; Mélon, Marlène; Collette, Fabienne ULiege et al

Conference (2017)

Chez les patients atteints de maladie d’Alzheimer (MA), on observe dès les stades débutants d’une part un phénomène d’anosognosie, qui peut être considéré comme une altération de la conscience de soi, et ... [more ▼]

Chez les patients atteints de maladie d’Alzheimer (MA), on observe dès les stades débutants d’une part un phénomène d’anosognosie, qui peut être considéré comme une altération de la conscience de soi, et d’autre part un dysfonctionnement des processus de monitoring mnésique [1]. En outre, l’interaction entre le soi et la mémoire (conférant un bénéfice mnésique pour les informations associées à soi), apparaît significativement altérée dans la MA. Dans la présente étude, nous avons examiné les relations entre l’anosognosie et le monitoring lors de la récupération en mémoire d’informations expérimentalement associées à soi. Nous avons évalué les processus de monitoring lors de la récupération en mémoire à l’aide d’une tâche expérimentale de 32 paires visage-prénom, ainsi que l’anosognosie à l’aide du questionnaire d’anosognosie dans la démence (AQD, [2]) chez 20 patients MA et 20 personnes âgées contrôles (AC). Durant la phase d’encodage, les paires visage-prénom ont été présentées aux participants soit comme des personnes faisant partie de leur famille (soi) soit comme des personnes faisant partie de la famille de l’expérimentateur (autrui). Ensuite, nous avons évalué les jugements de « sentiment de savoir » (FOK), les performances de rappel et de reconnaissance, ainsi que les jugements de confiance (JOC) des participants pour le nom de chaque personne lorsque son visage était présenté. Nos résultats ont confirmé l’altération de la conscience de soi (c’est-à-dire l’anosognosie mesurée par l’AQD), l’altération du bénéfice mnésique pour les informations associées à soi, ainsi que l’altération des processus de monitoring lors de la récupération en mémoire (FOK et JOC) chez les patients MA. Néanmoins, une modification de l’interaction entre le soi et les processus de monitoring chez ces patients a été observée uniquement au niveau des sentiments de confiance pour des souvenirs erronés. Nous avons également observé que l’anosognosie des troubles comportementaux était significativement corrélée à la proportion de sentiments de confiance pour des reconnaissances erronées sur les items associés à soi. En conclusion, notre étude suggère que l’altération de la conscience des troubles comportementaux chez les patients MA pourrait être liée à un déficit de monitoring des souvenirs liés à soi. C’est-à-dire que la conscience altérée du dysfonctionnement au quotidien pourrait s’appuyer sur des souvenirs personnels déformés. [less ▲]

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See detailThe frequency and influence of dementia risk factors in prodromal Alzheimer’s disease
Bos, Isabelle; Vos, Stephanie J.; Frölich, Lutz et al

in Neurobiology of Aging (2017), 56

We investigated whether dementia risk factors were associated with prodromal Alzheimer’s disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer’s Association ... [more ▼]

We investigated whether dementia risk factors were associated with prodromal Alzheimer’s disease (AD) according to the International Working Group-2 and National Institute of Aging-Alzheimer’s Association criteria, and with cognitive decline. 1394 subjects from with Mild Cognitive Impairment (MCI) from 14 different studies were classified according to these research criteria, based on cognitive performance and biomarkers. We compared the frequency of ten risk factors between the subgroups and used Cox-regression to examine the effect of risk factors on cognitive decline. Depression, obesity and hypercholesterolemia occurred more often in individuals with low-AD-likelihood, compared to those with a high-AD-likelihood. Only alcohol use increased the risk of cognitive decline, regardless of AD pathology. These results suggest that traditional risk factors for AD are not associated with prodromal AD or with progression to dementia, among subjects with MCI. Future studies should validate these findings and determine whether risk factors might be of influence at an earlier stage (i.e. preclinical) of AD. [less ▲]

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See detailThe neural bases of proactive and reactive control processes in normal aging
Manard, Marine ULiege; François, Sarah ULiege; Phillips, Christophe ULiege et al

in Behavioural Brain Research (2017), 320

Introduction. Research on cognitive control suggests an age-related decline in proactive control abilities (anticipatory control), whereas reactive control (following conflict detection) seems to remain ... [more ▼]

Introduction. Research on cognitive control suggests an age-related decline in proactive control abilities (anticipatory control), whereas reactive control (following conflict detection) seems to remain intact. As proactive and reactive control abilities are associated with specific brain networks, this study investigated age-related effects on the neural substrates associated with each kind of control. Methods. In an event-related fMRI study, a modified version of the Stroop task was administered to groups of 20 young and 20 older healthy adults. Based on the theory of dual mechanisms of control, the Stroop task has been built to induce proactive or reactive control depending on task context. Results. Behavioral results (p < .05) indicated faster processing of interfering items in the mostly incongruent (MI) than the mostly congruent (MC) context in both young and older participants. fMRI results showed that reactive control is associated with increased activity in left frontal areas for older participants. For proactive control, decreased activity in the bilateral anterior cingulate cortex was associated with more activity in the right middle frontal gyrus in the older than the younger group. Conclusion. These observations support the hypothesis that aging affects the neural networks associated with reactive and proactive cognitive control differentially. These age-related changes are very similar to those observed in young adults with low dopamine availability, suggesting that a general mechanism (prefrontal dopamine availability) may modulate brain networks associated with various kinds of cognitive control. [less ▲]

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See detailFluctuations of Attentional Networks and Default Mode Network during the Resting State Reflect Variations in Cognitive States: Evidence from a Novel Resting-state
Van Calster, Laurens ULiege; D'Argembeau, Arnaud ULiege; SALMON, Eric ULiege et al

in Journal of Cognitive Neuroscience (2017)

Neuroimaging studies have revealed the recruitment of a range of neural networks during the resting state, which might reflect a variety of cognitive experiences and processes occurring in an individual's ... [more ▼]

Neuroimaging studies have revealed the recruitment of a range of neural networks during the resting state, which might reflect a variety of cognitive experiences and processes occurring in an individual's mind. In this study, we focused on the default mode network (DMN) and attentional networks and investigated their association with distinct mental states when participants are not performing an explicit task. To investigate the range of possible cognitive experiences more directly, this study proposes a novel method of resting-state fMRI experience sampling, informed by a phenomenological investigation of the fluctuation of mental states during the resting state. We hypothesized that DMN activity would increase as a function of internal mentation and that the activity of dorsal and ventral networks would indicate states of top–down versus bottom–up attention at rest. Results showed that dorsal attention network activity fluctuated as a function of subjective reports of attentional control, providing evidence that activity of this network reflects the perceived recruitment of controlled attentional processes during spontaneous cognition. Activity of the DMN increased when participants reported to be in a subjective state of internal mentation, but not when they reported to be in a state of perception. This study provides direct evidence for a link between fluctuations of resting-state neural activity and fluctuations in specific cognitive processes. [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

in Cortex : A Journal Devoted to the Study of the Nervous System & Behavior (2016), 85

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 detailEVALUATING THE SPECIFICITY OF [18F]UCB-H FOR THE ISOFORM SV2A, COMPARED WITH ISOFORMS SV2B AND SV2C
Serrano Navacerrada, Maria Elisa ULiege; Aerts, Joël ULiege; Bahri, Mohamed Ali ULiege et al

Poster (2016, November 18)

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 detailIncreasing the salience of fluency cues does not reduce the recognition memory impairment in Alzheimer’s disease!
Simon, Jessica ULiege; Bastin, Christine ULiege; SALMON, Eric ULiege et al

in Journal of Neuropsychology (2016)

In Alzheimer’s disease (AD), it is now well established that recollection is impaired from the beginning of the disease, whereas findings are less clear concerning familiarity. One of the most important ... [more ▼]

In Alzheimer’s disease (AD), it is now well established that recollection is impaired from the beginning of the disease, whereas findings are less clear concerning familiarity. One of the most important mechanisms underlying familiarity is the sense of familiarity driven by processing fluency. In this study, we attempted to attenuate recognition memory deficits in AD by maximizing the salience of fluency cues in two conditions of a recognition memory task. In one condition, targets and foils have been created from the same pool of letters (Overlap condition). In a second condition, targets and foils have been derived from two separate pools of letters (No-Overlap condition), promoting the use of letter-driven visual and phonetic fluency. Targets and foils were low-frequency words. The memory tasks were performed by 15 patients with AD and 16 healthy controls. Both groups improved their memory performance in the No-Overlap condition compared to the Overlap condition. Patients with AD were able to use fluency cues during recognition memory as older adults did, but this did not allow to compensate for dysfunction of recognition memory processes. [less ▲]

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See detailThe influence of COMT on the neural substrates of short-term memory in normal aging
Manard, Marine ULiege; Salmon, Eric ULiege; Collette, Fabienne ULiege

Conference (2016, September 02)

Working memory dopaminergic modulation is generally expressed in healthy aging by an advantage for carriers of the Met allele at behavioral and brain activity levels. However, most tasks used did not ... [more ▼]

Working memory dopaminergic modulation is generally expressed in healthy aging by an advantage for carriers of the Met allele at behavioral and brain activity levels. However, most tasks used did not allow to easily disentangle the contribution of maintenance and manipulation processes. We explored the effect of COMT genotype on the maintenance process using a Sternberg memory task varying the amount of information presented, in young and older homozygous carriers for the Val and Met alleles of the COMT gene. Although no clear behavioral difference was observed between groups, patterns of cerebral activity indicate difficulties for Met older individuals to maintain stable representations. These results will be discussed in terms of dopaminergic contribution to stability/flexibility of cognitive processes during aging. [less ▲]

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See detailEffects of aging on task- and stimulus-related cerebral attention networks
Kurth, Sophie ULiege; Majerus, Steve ULiege; Bastin, Christine ULiege et al

in Neurobiology of Aging (2016), 44

Interactions between a dorsal attention (DAN) and a ventral attention cerebral network (VAN) have been reported in young participants during attention or short term memory (STM) tasks. Since it remains an ... [more ▼]

Interactions between a dorsal attention (DAN) and a ventral attention cerebral network (VAN) have been reported in young participants during attention or short term memory (STM) tasks. Since it remains an under-investigated question, age effects on DAN and VAN activity and their functional balance were explored during performance of a STM task. Older and young groups showed similar behavioral patterns of results. At the cerebral level, DAN activation increased as a function of increasing STM load in both groups, suggesting preserved activity in DAN during healthy aging. Age-related over-recruitment in regions of the DAN in the higher task load raised the question of compensation attempt versus less efficient use of neural resources in older adults. Lesser decrease of VAN activation with increasing load and decreased stimulus-driven activation in the VAN, especially in the higher load, in older participants suggested age-related reduced response in the VAN. However, functional connectivity measures showed that VAN was still functionally connected to the DAN in older participants. [less ▲]

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See detailThe influence of COMT on the neural substrates of short-term memory in normal aging
Collette, Fabienne ULiege; Manard, Marine ULiege; Salmon, Eric ULiege

Conference (2016, July 21)

Working memory dopaminergic modulation is generally expressed in healthy aging by an advantage for carriers of the Met allele at behavioral and brain activity levels. However, most tasks used did not ... [more ▼]

Working memory dopaminergic modulation is generally expressed in healthy aging by an advantage for carriers of the Met allele at behavioral and brain activity levels. However, most tasks used did not allow to easily disentangle the contribution of maintenance and manipulation processes. We explored the effect of COMT genotype on the maintenance process using a Sternberg memory task varying the amount of information presented, in young and older homozygous carriers for the Val and Met alleles of the COMT gene. Although no clear behavioral difference was observed between groups, patterns of cerebral activity indicate difficulties for Met older individuals to maintain stable representations. These results will be discussed in terms of dopaminergic contribution to stability/flexibility of cognitive processes during aging. [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 (2016, July 18)

The aim of this study was to investigate the impact of test format on recollection and familiarity in normal aging and in MCI. Seventy young participants, 65 younger-old, 53 older-old, and 13 MCIs were ... [more ▼]

The aim of this study was to investigate the impact of test format on recollection and familiarity in normal aging and in MCI. Seventy young participants, 65 younger-old, 53 older-old, and 13 MCIs were presented with forced-choice and yes/no visual recognition memory tasks with the Remember/Know/Guess paradigm. The young people had better recognition 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 detailDisrupted interaction between self and memory in patients with Alzheimer’s disease
Genon, Sarah ULiege; Salmon, Eric ULiege; Collette, Fabienne ULiege et al

Conference (2016, July)

In humans, self and memory processes interact as evidenced by the self reference (SRE) and self reference recollection effects (SRRE). However, in patients with Alzheimer’s disease (AD), this relationship ... [more ▼]

In humans, self and memory processes interact as evidenced by the self reference (SRE) and self reference recollection effects (SRRE). However, in patients with Alzheimer’s disease (AD), this relationship can be disrupted. This was evidenced by impaired SRE and SRRE in AD for recognition of adjectives previously judged for self-relevance, as well as recall of names of people previously linked to the self. For both materials, a qualitative impairment of the recollective experience for the self-related items was also observed in AD. A neuroimaging approach suggested that reduced SRE is related to decreased grey matter volume in the lateral prefrontal cortex (lPFC). Thus, retrieval of recent self-related memories is impaired in relation to altered high-order processes in lPFC in AD. [less ▲]

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See detailSubstrats neuronaux de l'encodage non réussi dans le vieillissement
François, Sarah ULiege; Angel, Lucie; Salmon, Eric ULiege et al

Conference (2016, May 27)

Objectifs En utilisant l'IRM fonctionnelle, nous nous sommes intéressés à l'effet de l'âge sur les substrats neuronaux de l'encodage non réussi – l'activation à l'encodage pour les items oubliés par la ... [more ▼]

Objectifs En utilisant l'IRM fonctionnelle, nous nous sommes intéressés à l'effet de l'âge sur les substrats neuronaux de l'encodage non réussi – l'activation à l'encodage pour les items oubliés par la suite. Méthodologie Dans un scanner IRM, nous avons soumis des volontaires (20 jeunes et 19 âgés) à une tâche de mémoire épisodique avec consignes d'encodage incident. Durant celle-ci, des dessins d'objets en noir et blanc leur étaient présentés. Il leur était demandé d'effectuer un jugement de taille sur ces objets. Ensuite, toujours dans le scanner, les objets de la phase d'encodage ainsi que de nouveaux objets leurs étaient présentés afin d'évaluer leur reconnaissance de ceux-ci. Pour ce faire, les volontaires effectuaient un jugement de Recollection/Familiarité/Nouveauté. Résultats Les résultats comportementaux montrent une recollection altérée mais une familiarité préservée chez nos volontaires âgés. L'analyse des résultats IRM a été effectuée selon un design évènementiel (SPM8), dans lequel nous avons comparé les aires cérébrales activées à l'encodage pour les items qui n'ont pas été reconnus ultérieurement et pour ceux qui ont donné lieu à un jugement de recollection (p<.001 non-corrigé). Dans les deux groupes, un pattern d'activation correspondant au réseau du mode par défaut (RMD). Chez les volontaires âgés, les résultats ont également mis en évidence une activation supplémentaire du réseau attentionnel fronto-pariétal. Ensuite, le contraste entre les activations pour les items qui n'ont pas été reconnus ultérieurement et ceux qui ont donné lieu à un jugement de familiarité a aussi mis en évidence des régions du RMD, mais dans une moindre mesure. En effet, les activités communes aux deux groupes d'âge n'ont montré qu'une activation du précuneus. Discussion Comparé à la recollection, l'oubli d'informations semble associé, à l'encodage, à un recrutement accru du RMD qui pourrait refléter une incapacité à mettre en place des processus d'encodage efficaces, à la fois chez les jeunes adultes et les adultes plus âgés. De plus, l'activation supplémentaire du réseau fronto-pariétal chez ces derniers pourrait indiquer un fonctionnement moins différencié des réseaux cérébraux associés à l'encodage en mémoire. Lorsque l'on compare l'oubli d'informations à la familiarité, l'activation moindre du RMD pourrait suggérer qu'un certain niveau d'activation du RMD (et donc la présence de pensées étrangères à la tâche) n'empêche pas forcément toute reconnaissance sur base d'un sentiment de familiarité. [less ▲]

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See detailSubstrats cérébraux du contrôle proactif et réactif dans le vieillissement non pathologique
Manard, Marine ULiege; François, Sarah ULiege; Salmon, Eric ULiege et al

Poster (2016, May 27)

Les recherches sur le contrôle cognitif proposent l’apparition d’un déclin lié à l’âge dans les capacités de contrôle proactif (forme anticipatoire de contrôle comportemental) alors que le contrôle ... [more ▼]

Les recherches sur le contrôle cognitif proposent l’apparition d’un déclin lié à l’âge dans les capacités de contrôle proactif (forme anticipatoire de contrôle comportemental) alors que le contrôle réactif (forme réactionnelle à la détection d’un conflit) semble rester intact [1]. Ces deux formes de contrôle ont été associées à des aires cérébrales différentes [2], cependant peu d’études ont étudié les effets de l’âge sur les régions cérébrales sous-tendant chacun de ces deux types de contrôle. Pour ce faire, une version adaptée de la tâche de Stroop a été administrée à 16 jeunes (18-30 ans) et 16 adultes (60-75 ans) en IRM fonctionnelle. Cette version de la tâche variait la quantité d’items interférents, permettant la création de trois contextes (Mostly Congruent « MC », Mostly Incongruent « MI » et Neutre) favorisant respectivement la mise en place des deux types de contrôle (réactif = congruent / proactif = incongruent). Les analyses ont été réalisées avec SPM8 (p<.001 non-corrigé). Les résultats comportementaux révèlent un traitement plus rapide de l’interférence dans le contexte « MI » que « MC » pour les jeunes adultes uniquement. Au niveau cérébral, le traitement de l’interférence en MI semble associé à une diminution d’activité (surtout à droite) dans les régions frontales et temporales chez les volontaires âgés par rapport aux plus jeunes, alors qu’en MC, les âgés montrent une augmentation d’activité bilatérale au niveau frontal. Ainsi, les résultats comportementaux montrent que les adultes âgés semblent avoir plus de difficultés à implémenter un contrôle proactif (associé à une diminution d’activité) que les jeunes dans les régions sous-tendant la performance à cette tâche. Cependant, le recrutement supplémentaire de régions frontales observé lors du contexte MC postulé pour favoriser le contrôle réactif, suggère la présence de mécanismes de compensation. Pour conclure, le vieillissement semble affecter de manière différentielle l’activité des régions cérébrales sous-tendant les différents types de contrôle. [less ▲]

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Peer Reviewed
See detailThe influence of COMT single nucleotide polymorphism (rs4680) on the neural substrates of working memory representations maintenance in healthy aging
Manard, Marine ULiege; François, Sarah ULiege; Bahri, Mohamed Ali ULiege et al

Poster (2016, May 10)

The COMT val108/158met polymorphism was associated to the dopaminergic modulation in the brain, and therefore stimulated research on its influence for cognitive functioning and particularly working memory ... [more ▼]

The COMT val108/158met polymorphism was associated to the dopaminergic modulation in the brain, and therefore stimulated research on its influence for cognitive functioning and particularly working memory. First, a general advantage of carrying the met allele was reported. However, many studies used tasks that did not allow efficiently assessing the contribution of manipulation and maintenance processes in working memory, leading to divergent results, in both young and older populations, resulting in debates about the exact phenotypic effect of the COMT polymorphism. Using fMRI, this study was designed to assess the potential effect of the COMT polymorphism on age-related differences in working memory representations maintenance abilities (Sternberg paradigm). Partial Least Squares method was used to determine the brain-behavior correlations at low, intermediate, and high cognitive demands among young and older groups, homozygous for the val or for the met allele. First, young val/val showed some disadvantages at brain and behavioral level compared to their m/m counterparts. However, in older adults subgroups, the m/m participants tended to show greater age-related difference (when compared to younger adults with similar genotype), suggesting an advantage in carrying the val allele when dopamine signaling is not at optimal efficiency (optimal: young/middle adulthood vs suboptimal: childhood or older ages). These results will be discussed in regard to compensating theories and dopaminergic models accounting for the potential effect of COMT polymorphism on stability/flexibility abilities. [less ▲]

Detailed reference viewed: 137 (14 ULiège)