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See detailHunting down the source: how amnesic patients avoid fluency-based memory errors
Geurten, Marie ULiege; Bastin, Christine ULiege; Salmon, Eric ULiege et al

in Neuropsychology (in press)

Objective: The primary aim of this study was to test whether differences in the ability of amnesic and healthy participants to detect alternative sources of fluency can account for differences observed in ... [more ▼]

Objective: The primary aim of this study was to test whether differences in the ability of amnesic and healthy participants to detect alternative sources of fluency can account for differences observed in the use of fluency as a cue for memory. Method: Patients with severe memory deficits and matched controls were presented with three forced-choice recognition tests. In each test, an external source of fluency was provided by manipulating the perceptual quality of the studied items during the test phase. The detectability of the perceptual manipulation varied in each test (i.e., a 10%, 20%, or 30% contrast reduction were given). Results: The results indicated that all participants were able to rely on fluency when making recognition decisions as long as the perceptual manipulation remained unnoticed. Interestingly, our data also revealed that the level of contrast reduction at which the alternative source is detected differs between healthy controls and amnesic patients. Specifically, patients with amnesia appeared to disqualify fluency as a cue for memory even when the contrast reduction was moderate while healthy participants only disqualified fluency when the contrast reduction was clearly visible. Conclusion: Overall, our results seem to suggest that the ability to use fluency is probably not impaired in amnesia but undergo metacognitive changes resulting in the implementation of explicit or implicit strategies aiming at tracking alternative sources in order to reduce memory errors. [less ▲]

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See detailDo Alzheimer’s disease patients benefit from prior-knowledge in associative recognition memory?
Delhaye, Emma ULiege; Folville, Adrien ULiege; Simoes Loureiro, Isabelle et al

in Journal of the International Neuropsychological Society (in press)

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See detailEvaluating the In Vivo Specificity of [18F]UCB-H for the SV2A Protein, Compared with SV2B and SV2C in Rats Using microPET.
Serrano Navacerrada, Maria Elisa ULiege; Becker, Guillaume ULiege; Bahri, Mohamed Ali ULiege et al

in Molecules (2019), 24(9), 1705

The synaptic vesicle protein 2 (SV2) is involved in synaptic vesicle trafficking. The SV2A isoform is the most studied and its implication in epilepsy therapy led to the development of the first SV2A PET ... [more ▼]

The synaptic vesicle protein 2 (SV2) is involved in synaptic vesicle trafficking. The SV2A isoform is the most studied and its implication in epilepsy therapy led to the development of the first SV2A PET radiotracer [18F]UCB-H. The objective of this study was to evaluate in vivo, using microPET in rats, the specificity of [18F]UCB-H for SV2 isoform A in comparison with the other two isoforms (B and C) through a blocking assay. Twenty Sprague Dawley rats were pre-treated either with the vehicle, or with specific competitors against SV2A (levetiracetam), SV2B (UCB5203) and SV2C (UCB0949). The distribution volume (Vt, Logan plot, t* 15 min) was obtained with a population-based input function. The Vt analysis for the entire brain showed statistically significant differences between the levetiracetam group and the other groups (p < 0.001), but also between the vehicle and the SV2B group (p < 0.05). An in-depth Vt analysis conducted for eight relevant brain structures confirmed the statistically significant differences between the levetiracetam group and the other groups (p < 0.001) and highlighted the superior and the inferior colliculi along with the cortex as regions also displaying statistically significant differences between the vehicle and SV2B groups (p < 0.05). These results emphasize the in vivo specificity of [18F]UCB-H for SV2A against SV2B and SV2C, confirming that [18F]UCB-H is a suitable radiotracer for in vivo imaging of the SV2A proteins with PET. [less ▲]

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See detailHow amnesic patients avoid fluency-based memory errors
Geurten, Marie ULiege; Bastin, Christine ULiege; Salmon, Eric ULiege et al

Poster (2019)

The primary aim of this study was to test whether differences in the ability of amnesic and healthy participants to detect alternative sources of fluency can account for differences observed in the use of ... [more ▼]

The primary aim of this study was to test whether differences in the ability of amnesic and healthy participants to detect alternative sources of fluency can account for differences observed in the use of fluency as a cue for memory. To this end, patients with severe memory deficits and matched controls were presented with three forced-choice recognition tests. In each test, an external source of fluency was provided by manipulating the perceptual quality of the studied items during the test phase. The detectability of the perceptual manipulation varied in each test (i.e., a 10%, 20%, or 30% contrast reduction were given). The results indicated that all participants were able to rely on fluency when making recognition decisions as long as the perceptual manipulation remained unnoticed. Interestingly, our data also revealed that the level of contrast reduction at which the alternative source is detected differs between healthy controls and amnesic patients. Specifically, patients with amnesia appeared to disqualify fluency as a cue for memory even when the contrast reduction was moderate while healthy participants only disqualified fluency when the contrast reduction was clearly visible. Overall, our results seem to suggest that the ability to use fluency is probably not impaired in amnesia but undergo metacognitive changes resulting in the implementation of explicit or implicit strategies aiming at tracking alternative sources in order to reduce memory errors. [less ▲]

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See detailAging reduces the circadian modulation of cortical reactivity during sleep loss and modifies its link with cognition
Gaggioni, Giulia ULiege; Ly, Julien; Muto, Vincenzo ULiege et al

in Neurobiology of Aging (2019), in press

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See detailAn Integrative Memory model of recollection and familiarity to understand memory deficits
Bastin, Christine ULiege; Besson, Gabriel ULiege; Simon, Jessica ULiege et al

in Behavioral and Brain Sciences (2019)

Humans can recollect past events in details (recollection) and/or know that an object, person or place has been encountered before (familiarity). During the last two decades, there has been intense debate ... [more ▼]

Humans can recollect past events in details (recollection) and/or know that an object, person or place has been encountered before (familiarity). During the last two decades, there has been intense debate about how recollection and familiarity are organized in the brain. Here, we propose an Integrative Memory model which describes the distributed and interactive neurocognitive architecture of representations and operations underlying recollection and familiarity. In this architecture, the subjective experience of recollection and familiarity arises from the interaction between core systems storing particular kinds of representations shaped by specific computational mechanisms and an attribution system. By integrating principles from current theoretical views about memory functioning, we provide a testable framework to refine the prediction of deficient versus preserved mechanisms in memory-impaired populations. The case of Alzheimer’s disease is considered as an example because it entails progressive lesions starting with limited damage to core systems before invading step-by-step most parts of the model-related network. We suggest a chronological scheme of cognitive impairments along the course of Alzheimer’s disease, where the inaugurating deficit would relate early neurodegeneration of the perirhinal/anterolateral entorhinal cortex to impaired familiarity for items that need to be discriminated as viewpoint-invariant conjunctive entities. The Integrative Memory model can guide future neuropsychological and neuroimaging studies aiming to understand how such a network allows humans to remember past events, to project into the future and possibly also to share experiences. [less ▲]

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See detailEfficacy of Cognitive Rehabilitation in Alzheimer Disease: A 1-Year Follow-Up Study
Germain, Sophie; WOJTASIK, Vinciane ULiege; LEKEU, Françoise ULiege et al

in Journal of Geriatric Psychiatry and Neurology (2019), 32(1), 16-23

Introduction: The benefit of cognitive rehabilitation (CR) for patients with early-stage Alzheimer disease (AD) remains difficult to assess. Method: An observational, prospective study was conducted in a ... [more ▼]

Introduction: The benefit of cognitive rehabilitation (CR) for patients with early-stage Alzheimer disease (AD) remains difficult to assess. Method: An observational, prospective study was conducted in a sample of 52 patients with AD included in a clinical, individualized CR program. Cognitive rehabilitation consisted of 1 weekly session during 3 months at home, followed by 1 monthly contact for 9 months. Rehabilitation techniques were used by experienced therapists to adapt activities important for the patient. Evaluation of patient’s dependence in activities and objective and subjective caregiver’s burden was performed with a research quantitative scale immediately after the intervention and at 6-month and 1-year follow-up. Results: Analyses with repeated measure analysis of variance showed decreased patient’s dependence for adapted activities at 3 months, 6 months, and 1 year. Objective and subjective percentage of caregiver’s burden was also decreased at all evaluations with our research functional scale, while there was no change on Zarit’s burden scale. Global cognition slightly decreased over 1 year. Conclusions: This observational study in a clinical setting is in line with the benefit of CR for patients with mild AD reported in recent randomized controlled trials. The benefit obtained for adapted activities remained after 1 year, even if global cognition declined. Moreover caregiver’s burden related to all individually relevant daily activities (from a list of 98) evaluated within the CR program was decreased after 1 year. Those preliminary results emphasize the importance of choice for the measurement instrument to report CR efficacy and claim for further validation of such tools. [less ▲]

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See detailQuantification of [18F]UCB-H Binding in the Rat Brain: From Kinetic Modelling to Standardised Uptake Value
Serrano Navacerrada, Maria Elisa ULiege; Bahri, Mohamed Ali ULiege; Becker, Guillaume ULiege et al

in Molecular Imaging and Biology (2018)

Purpose: [18F]UCB-H is a specific positron emission tomography (PET) biomarker for the Synaptic Vesicle protein 2A (SV2A), the binding site of the antiepileptic drug levetiracetam. With a view to ... [more ▼]

Purpose: [18F]UCB-H is a specific positron emission tomography (PET) biomarker for the Synaptic Vesicle protein 2A (SV2A), the binding site of the antiepileptic drug levetiracetam. With a view to optimising acquisition time and simplifying data analysis with this radiotracer, we compared two parameters: the distribution volume (Vt) obtained from Logan graphical analysis using a Population-Based Input Function, and the Standardised Uptake Value (SUV). Procedures: Twelve Sprague Dawley male rats, pre-treated with three different doses of levetiracetam were employed to develop the methodology. Three additional kainic acid (KA) treated rats (temporal lobe epilepsy model) were also used to test the procedure. Image analyses focused on: (i) length of the dynamic acquisition (90 versus 60 min); (ii) correlations between Vt and SUV over 20-min consecutive time-frames; (iii) and (iv) evaluation of differences between groups using the Vt and the SUV; and (v) preliminary evaluation of the methodology in the KA epilepsy model. Results: A large correlation between the Vt issued from 60 to 90-min acquisitions was observed. Further analyses highlighted a large correlation (r 9 0.8) between the Vt and the SUV. Equivalent differences between groups were detected for both parameters, especially in the 20–40 and 40– 60-min time-frames. The same results were also obtained with the epilepsy model. Conclusions: Our results enable the acquisition setting to be changed from a 90-min dynamic to a 20-min static PET acquisition. According to a better image quality, the 20–40-min time-frame appears optimal. Due to its equivalence to the Vt, the SUV parameter can be considered in order to quantify [18F]UCB-H uptake in the rat brain. This work, therefore, establishes a starting point for the simplification of SV2A in vivo quantification with [18F]UCB-H, and represents a step forward to the clinical application of this PET radiotracer. [less ▲]

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See detailSleep fragmentation is associated with brain tau but not amyloid-β burden in healthy older adults
Chylinski, Daphné ULiege; Rudzik, Franziska; Coppieters't Wallant, Dorothe ULiege et al

Conference (2018, November 09)

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See detailArousals during sleep are associated with brain tau burden in healthy older individuals
Chylinski, Daphné ULiege; Rudzik, Franziska; Coppieters't Wallant, Dorothe ULiege et al

Poster (2018, October 19)

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See detailTHE SV2A PROTEIN: IMAGING SYNAPTIC DENSITY DURING THE PROGRESSION OF THE TEMPORAL LOBE EPILEPSY IN THE KASE RAT MODEL
Serrano Navacerrada, Maria Elisa ULiege; Bahri, Mohamed Ali ULiege; Becker, Guillaume ULiege et al

Poster (2018, October 18)

Introduction The temporal lobe epilepsy (TLE) is the most common epileptic disorder. New antiepileptic drugs target the Synaptic Vesicle protein 2A (SV2A) (1). Nevertheless, the prevailing literature ... [more ▼]

Introduction The temporal lobe epilepsy (TLE) is the most common epileptic disorder. New antiepileptic drugs target the Synaptic Vesicle protein 2A (SV2A) (1). Nevertheless, the prevailing literature addressing the relation between this protein and the epilepsy is limited (2, 3). This study provides insights on the role of the SV2A protein during the four stages of TLE (4, 5), throughout its in vivo study with the [18F]UCB-H radiotracer (6). Methods Twenty-four male Sprague-Dawley were subjected to multiple injections (7) of i) Saline (Sham), or ii) 5mg/kg of Kainic Acid (KA). The rats not reacting to KA (NKA) were also scanned. In each TLE stages, a [18F]UCB-H dynamic scan was performed, followed by a T2-structural MRI. EEG recordings were performed to determine the number of crises. Data processing was done with PMOD 3.6. Results were expressed as SUV and statistically analyzed with the SPSS and the SPM. Results During the acute phase, statistically significant differences were found between Sham and KA in striatum, cerebellum, and medulla. In the latent phase, these SUV differences were detected between the NKA and KA in the same regions along with hippocampus and thalamus. When the spontaneous crises started, these group differences became statistically significant in all the regions but the cortex. During the chronic phase, all the regions showed statistically significant differences between groups. Furthermore, the voxel-wise analysis highlighted statistically significant differences in voxels at the level of amygdala and hippocampus. Conclusions These results show that [18F]UCB-H is able to detect early modifications in SV2A expression (3 days after the TLE model creation), in particular in regions implicated in the epileptic process. This radiotracer can potentially be used as a suitable biomarker for the early detection of the epileptic disease, being able to distinguish between stages in this neurodegenerative disease. [less ▲]

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