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See detailIncreased cerebral functional connectivity underlying the antinociceptive effects of hypnosis
Faymonville, Marie-Elisabeth ULg; Roediger, Laurence ULg; Del Fiore, Guy et al

in Cognitive Brain Research (2003), 17(2), 255-262

The neural mechanisms underlying the antinociceptive effects of hypnosis are not well understood. Using positron emission tomography (PET), we recently showed that the activity in the anterior cingulate ... [more ▼]

The neural mechanisms underlying the antinociceptive effects of hypnosis are not well understood. Using positron emission tomography (PET), we recently showed that the activity in the anterior cingulate cortex (midcingulate area 24a') covaries with the hypnosis-induced reduction of affective and sensory responses to noxious thermal stimulation [Faymonville et al., Anesthesiology 92 (2000) 1257-1267]. In the present study, we assessed changes in cerebral functional connectivity related to the hypnotic state, compared to simple distraction and the resting state. Nineteen highly hypnotizable right-handed volunteers were studied using (H2O)-O-15-PET. The experimental conditions were hot noxious or warm non-noxious stimulation of the right hand during resting state, mental imagery and hypnotic state. Using a psychophysiological interaction analysis, we identified brain areas that would respond to noxious stimulations under the modulatory action of the midcingulate cortex in, and only in, the hypnotic state. Hypnosis, compared to the resting state, reduced pain perception by 50%. Pain perception during rest and mental imagery was not significantly different. Analysis of PET data showed that the hypnotic state, compared to normal alertness (i.e., rest and mental imagery), significantly enhanced the functional modulation between midcingulate cortex and a large neural network encompassing bilateral insula, pregenual anterior cingulate cortex, pre-supplementary motor area, right prefrontal cortex and striatum, thalamus and brainstem. These findings point to a critical role for the midcingulate cortex in the modulation of a large cortical and subcortical network underlying its influence on sensory, affective, Cognitive and behavioral aspects of nociception, in the specific context of hypnosis. (C) 2003 Elsevier B.V. All rights reserved. [less ▲]

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See detailRadiosynthèses d'antagonistes des récepteurs 5-HT1A.
Defraiteur, C.; Plenevaux, Alain ULg; Lemaire, Christian ULg et al

Poster (2003, June 13)

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See detailMise au point de sondes pour l'étude du système sérotoninergique par tomographie à émission de positons (TEP)
Giacomelli, Fabrice ULg; Lemaire, Christian ULg; Plenevaux, Alain ULg et al

Poster (2003, June 13)

La quantification de la vitesse de biosynthèse de la sérotonine ainsi que l'étude in vivo chez l'homme sont, du fait de l'implication cruciale des neurones sérotoninergiques dans de nombreuses fonctions ... [more ▼]

La quantification de la vitesse de biosynthèse de la sérotonine ainsi que l'étude in vivo chez l'homme sont, du fait de l'implication cruciale des neurones sérotoninergiques dans de nombreuses fonctions et pathologies cérébrales, des domaines d'études fondamentaux pour lesquels la TEP constitue un outil de choix. Ces différentes expérimentations peuvent être conduites suivant deux optiques: (i) emploi d'un traceur capable de suivre la chaîne métabolique du tryptophane conduisant à la sérotonine tout en évitant les autres voies métaboliques. (ii) utilisation d'un inhibiteur de la tryptophane hydroxylase (TPOH), enzyme limitante du processus. [less ▲]

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See detailRadiosynthèse de dérivés du 7-[18F]fluoroindole
Otabashi, Muhammad ULg; Giacomelli, Fabrice ULg; Lemaire, Christian ULg et al

Poster (2003, June 13)

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See detailWhole-body tumor imaging using PET and 2-18F-fluoro-l-tyrosine: Preliminary evaluation and comparison with 18F-FDG
Hustinx, Roland ULg; Lemaire, Christian ULg; Jerusalem, Guy ULg et al

in Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine (2003), 44(4), 533-539

18F-FDG PET imaging is now established as a valuable tool for evaluating cancer patients. However, a limitation of 18F-FDG is its absence of specificity for tumor. Both protein synthesis and amino acid ... [more ▼]

18F-FDG PET imaging is now established as a valuable tool for evaluating cancer patients. However, a limitation of 18F-FDG is its absence of specificity for tumor. Both protein synthesis and amino acid transport are enhanced in most tumor cells, but their metabolism is less affected in inflammation. We therefore decided to evaluate the ability of PET with 2-18F-fluoro-L-tyrosine (18F-TYR) to visualize cancer lesions in patients compared with 18F-FDG PET. Methods: 18F-FDG PET and 18F-TYR PET were performed on 23 patients with histologically proven malignancies (11 non-small cell lung cancers (NSCLCs), 10 lymphomas, and 2 head and neck carcinomas). Fully corrected, whole-body PET studies were obtained on separate days. 18F-FDG studies were performed after routine clinical fashion. 18F-TYR studies were started 36 ± 6 min after tracer injection and a second scan centered over a reference lesion was acquired after completion of the whole-body survey-on average, 87 min after injection. Standardized uptake values (SUVs) were calculated for all abnormal foci and for various normal structures. Results were compared with pathologic or correlative studies. Results: 18F-FDG PET correctly identified 54 malignant lesions, among which 36 were also visualized with 18F-TYR (67%). 18F-TYR did not detect any additional lesion. Tumor SUVs (SUVbw, 5.2 vs. 2.5), tumor-to-muscle (7.4 vs. 2.7), and tumor-to-mediastinum activity ratios (3 vs. 1.4) were higher with 18F-FDG than with 18F-TYR. Two of 11 NSCLCs and 4 of 10 lymphomas were understaged with 18F-TYR compared with 18F-FDG. Although the NSCLC lesions missed by 18F-TYR PET were small, several large lymphoma lesions did not accumulate the tracer. In 4 patients, 18F-TYR-positive lesions coexisted with 18F-TYR-negative lesions. There was a high physiologic 18F-TYR uptake by the pancreas (average SUVbw, 10.3) and the liver (average SUVbw, 6.3). Muscle and bone marrow uptakes were also higher with 18F-TYR than with 18F-FDG: average SUVbw, 1 versus 0.7 and 2.6 versus 1.8, respectively. There was no change over time in the 18F-TYR uptake by the tumors or the normal structures. Conclusion: 18F-TYR PET is not superior to 18F-FDG PET for staging patients with NSCLC and lymphomas. [less ▲]

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See detailNeural correlates of "hot" and "cold" emotional processing : a multilevel approach to the functional anatomy of emotion
Schaefer, Alexandre; Collette, Fabienne ULg; Philippot, Pierre et al

in Neuroimage (2003), 18(4), 938-949

The neural correlates of two hypothesized emotional processing modes, i.e., schematic and propositional modes, were investigated with positron emission tomography. Nineteen subjects performed an emotional ... [more ▼]

The neural correlates of two hypothesized emotional processing modes, i.e., schematic and propositional modes, were investigated with positron emission tomography. Nineteen subjects performed an emotional mental imagery task while mentally repeating sentences linked to the meaning of the imagery script. In the schematic conditions, participants repeated metaphoric sentences, whereas in the propositional conditions, the sentences were explicit questions about specific emotional appraisals of the imagery scenario. Five types of emotional scripts were proposed to the subjects (happiness, anger, affection, sadness, and a neutral scenario). The results supported the hypothesized distinction between schematic and propositional emotional processing modes. Specifically, schematic mode was associated with increased activity in the ventromedial prefrontal cortex whereas propositional mode was associated with activation of the anterolateral prefrontal cortex. In addition, interaction analyses showed that schematic versus propositional processing of happiness (compared with the neutral scenario) was associated with increased activity in the ventral striatum whereas "schematic anger" was tentatively associated with activation of the ventral pallidum. (C) 2003 Elsevier Science (USA). All rights reserved. [less ▲]

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See detailEffects of Alzheimer's disease on the recognition of novel versus familiar words : Neuropsychological and clinico-metabolic data
Lekeu, Françoise ULg; Van der Linden, Martial ULg; Degueldre, Christian ULg et al

in Neuropsychology (2003), 17(1), 143-154

This study explored recognition memory performance for novel versus familiar words in Alzheimer's disease (AD) patients and normal controls (NCs), using an adaptation of E. Tulving and N. Kroll's (1995 ... [more ▼]

This study explored recognition memory performance for novel versus familiar words in Alzheimer's disease (AD) patients and normal controls (NCs), using an adaptation of E. Tulving and N. Kroll's (1995) procedure. Results showed that both groups exhibited more hits and more false alarms for familiar than for novel words. The groups did not differ in the recognition of familiar words, reflecting preserved familiarity processes in AD. However, AD patients made more false alarms than NCs in the recognition of novel words, reflecting impairment of recollection processes in AD. A positron emission tomography analysis of clinico-metabolic correlations in AD patients showed a correlation between recognition of novel words and right hippocampal activity, whereas recognition of familiar words was more related to metabolic activity in the left posterior orbitofrontal cortex. [less ▲]

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See detailRadiosynthesis of 7-[18F]fluoroindole derivatives.
Otabashi, Muhammad ULg; Giacomelli, Fabrice ULg; Lemaire, Christian ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2003), 46

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See detailSimple device for the radiosynthesis of [carbonyl-11C]amides, esters and ketones using carbon-11 monoxide.
Brichard, L.; Del Fiore, G.; Lemaire, Christian ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2003), 46

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See detailSynthesis of [18F]fluorinated a-methyl-a-amino acids by phase transfer catalysis for potential PET application.
Wouters, L.; Lemaire, Christian ULg; Plenevaux, Alain ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2003), 46

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See detailDevelopment and evaluation of an automated atlas-based image analysis method for microPET studies of the rat brain.
Rubins, Daniel J.; Melega, William P.; Lacan, Goran et al

in NeuroImage (2003), 20(4), 2100-18

An automated method for placement of 3D rat brain atlas-derived volumes of interest (VOIs) onto PET studies has been designed and evaluated. VOIs representing major structures of the rat brain were ... [more ▼]

An automated method for placement of 3D rat brain atlas-derived volumes of interest (VOIs) onto PET studies has been designed and evaluated. VOIs representing major structures of the rat brain were defined on a set of digitized cryosectioned images of the rat brain. For VOI placement, each PET study was registered with a synthetic PET target constructed from the VOI template. Registration was accomplished with an automated algorithm that maximized the mutual information content of the image volumes. The accuracy and precision of this method for VOI placement was determined using datasets from PET studies of the striatal dopamine and hippocampal serotonin systems. Each evaluated PET study could be registered to at least one synthetic PET target without obvious failure. Registration was critically dependent upon the initial position of the PET study relative to the synthetic PET target, but not dependent on the amount of synthetic PET target smoothing. An evaluation algorithm showed that resultant radioactivity concentration measurements of selected brain structures had errors=2% due to misalignment with the corresponding VOI. Further, radioligand binding values calculated from these measurements were found to be more precise than those calculated from measurements obtained with manually drawn regions of interest (ROIs). Overall, evaluation results demonstrated that this atlas-derived VOI method can be used to obtain unbiased measurements of radioactivity concentration from PET studies. Its automated features, and applicability to different radioligands and brain regions, will facilitate quantitative rat brain PET assessment procedures. [less ▲]

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See detailThe neural substrates of the central executive: Exploration of the updating and shifting processes
Collette, Fabienne ULg; Van der Linden, Martial ULg; Delchambre, Marie et al

Conference (2002, December)

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See detailBrain function in the vegetative state
Laureys, Steven ULg; Antoine, S.; Boly, Mélanie ULg et al

in Acta Neurologica Belgica (2002), 102(4), 177-185

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates ... [more ▼]

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction. [less ▲]

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See detailCortical processing of noxious somatosensory stimuli in the persistent vegetative state
Laureys, Steven ULg; Faymonville, Marie-Elisabeth ULg; Peigneux, Philippe ULg et al

in NeuroImage (2002), 17(2), 732-741

The persistent vegetative state (PVS) is a devastating medical condition characterized by preserved wakefulness contrasting with absent voluntary interaction with the environment. We used positron ... [more ▼]

The persistent vegetative state (PVS) is a devastating medical condition characterized by preserved wakefulness contrasting with absent voluntary interaction with the environment. We used positron emission tomography to assess the central processing of noxious somatosensory stimuli in the PVS. Changes in regional cerebral blood flow were measured during high-intensity electrical stimulation of the median nerve compared with rest in 15 nonsedated patients and in 15 healthy controls. Evoked potentials were recorded simultaneously. The stimuli were experienced as highly unpleasant to painful in controls. Brain glucose metabolism was also studied with [F-18]fluorodeoxyglucose in resting conditions. In PVS patients, overall cerebral metabolism was 40% of normal values. Nevertheless, noxious somatosensory stimulation-activated midbrain, contralateral thalamus, and primary somatosensory cortex in each and every PVS patient, even in the absence of detectable cortical evoked potentials. Secondary somatosensory, bilateral insular, posterior parietal, and anterior cingulate cortices did not show activation in any patient. Moreover, in PVS patients, the activated primary somatosensory cortex was functionally disconnected from secondary somatosensory, bilateral posterior parietal, premotor, polysensory superior temporal, and prefrontal cortices. In conclusion, somatosensory stimulation of PVS patients, at intensities that elicited pain in controls, resulted in increased neuronal activity in primary somatosensory cortex, even if resting brain metabolism was severely impaired. However, this activation of primary cortex seems to be isolated and dissociated from higher-order associative cortices. (C) 2002 Elsevier Science (USA). [less ▲]

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See detailThe neural substrates of the central executive: Exploration of the updating and shifting processes
Collette, Fabienne ULg; Van der Linden, Martial ULg; Delchambre, Marie et al

Conference (2002, September)

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See detailEpimerization study on [18F]FDG produced by an alkaline hydrolysis on solid support under stringent conditions
Mosdzianowski, C.; Lemaire, Christian ULg; Simoens, F. et al

in Applied Radiation & Isotopes (2002), 56(6), 871-875

Since 1998, routine [18F]FDG syntheses are being carried out by alkaline hydrolysis on a solid support, i.e. the labeled intermediate is trapped on a tC18 solid phase extraction cartridge, purified and ... [more ▼]

Since 1998, routine [18F]FDG syntheses are being carried out by alkaline hydrolysis on a solid support, i.e. the labeled intermediate is trapped on a tC18 solid phase extraction cartridge, purified and finally hydrolyzed within the cartridge, at room temperature, using sodium hydroxide. The present study demonstrated that no epimerization of [18F]FDG to [18F]FDM occurs even when 12 N NaOH is used and when the hydrolysis time is extended up to 1 h. The alkaline hydrolysis on solid support appears to be a simple method leading to [18F]FDG with high purity. [less ▲]

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See detailA PET investigation of lexicality and phonotactic frequency in oral language processing
Majerus, Steve ULg; Collette, Fabienne ULg; Van der Linden, Martial ULg et al

in Cognitive Neuropsychology (2002), 19(4), 343-360

Lexicality and phonotactic frequency effects are observed in many cognitive studies on language processing, but little is known about their underlying neural substrates, especially with regard to ... [more ▼]

Lexicality and phonotactic frequency effects are observed in many cognitive studies on language processing, but little is known about their underlying neural substrates, especially with regard to phonotactic frequency effects. Here, we conducted a positron emission tomography (PET) study in which 11 right-handed volunteers had either to repeat or to listen to lists of words, high phonotactic frequency nonwords, and low phonotactic frequency nonwords. The comparison of word versus nonword processing consistently confirmed previous findings of left temporal and prefrontal activations classically ascribed to lexicosemantic processing. Higher activation was found in the right posterior superior temporal gyrus when comparing high phonotactic frequency nonwords to words, but not when comparing low phonotactic frequency nonwords to words. We propose that this region is implicated in the formation of temporary phonological representations for high-probability phonological events, which may support processing of high phonotactic frequency nonwords [less ▲]

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See detailShort- and long-term effects of p-ethynylphenylalanine on brain serotonin levels
Zimmer, Luc; Luxen, André ULg; Giacomelli, Fabrice ULg et al

in Neurochemical Research (2002), 27(4), 269-275

Changes in tissue and extracellular serotonin (5-HT) in raphe dorsalis, raphe medialis and in their main projections areas (hippocampus, striatum and frontal cortex) were investigated at short and long ... [more ▼]

Changes in tissue and extracellular serotonin (5-HT) in raphe dorsalis, raphe medialis and in their main projections areas (hippocampus, striatum and frontal cortex) were investigated at short and long-term times after single injection (5 mg/kg ip) of a novel tryptophan hydroxylase inhibitor, p-ethynylphenylalanine (p-EPA). The 5-HT tissue concentration decreased significantly in raphe nuclei, 30 min post-injection and for 4 days, whereas it decreased from 24 hours post-injection in the 5-HT projections. Normal 5-HT levels reappeared after 12 days post-injection in all areas. Moreover, in the projection areas, the extracellular 5-HT levels decreased rapidly, 90, 40 and 30 min after p-EPA injection, in hippocampus, striatum and frontal cortex, respectively. Decreased accumulation of 5-hydroxytryptophan (5-HTP) under NSD-101 perfusion in the serotoninergic projections after p-EPA injection, confirmed the direct inhibitory effect of the drug on the tryptophan hydroxylase activity. These results demonstrated that p-EPA is a useful pharmacological tool which powerfully, acutely and irreversibly reduces the 5-HT levels. [less ▲]

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See detailEffect of endogenous serotonin on the binding of the 5-HT1A PET ligand 18 F in the rat hippocampus: kinetic b measurements combined with microdialysis
Zimmer, Luc; Mauger, Gweltas; Le Bars, Didier et al

in Journal of Neurochemistry (2002), 80(2), 278-286

By using a combination of an original beta(+)-sensitive intracerebral probe and microdialysis, the effect of increased endogenous serotonin on specific binding of F-18-MPPF [4-(2'-methoxy-phenyl)-1-[2'-[N ... [more ▼]

By using a combination of an original beta(+)-sensitive intracerebral probe and microdialysis, the effect of increased endogenous serotonin on specific binding of F-18-MPPF [4-(2'-methoxy-phenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido]ethyl]piperazine] to the serotonin-1A (5-HT1A) receptors was investigated in the hippocampus of the anaesthetized rat. Our beta-sensitive probe prototype was sensitive enough to obtain Specific F-18-MPPF time-activity curves in the rodent (hippocampus/cerebellum ratio approximate to 2). The serotonin neuronal release was pharmacologically enhanced using fenfluramine at three different doses (1, 2 and 10 mg/kg intravenous) multiplying by 2-15 the extracellular serotonin in the hippocampus. These extracellular variations of extracellular serotonin resulted in dose-ranging decreases in F-18-MPPF-specific binding in the same rat. Our results showed for the first time that F-18-MPPF binding could be modulated by modifications of extracellular serotonin in the rat hippocampus. These results were confirmed by the enhancement of extracellular radioactivity collected in dialysates after the displacement of F-18-MPPF by fenfluramine. After modelization, F-18-MPPF binding could constitute an interesting radiotracer for positron emission tomography in evaluating the serotonin endogenous levels in limbic areas of the human brain. [less ▲]

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See detailModeling [F-18]MPPF positron emission tomography kinetics for the determination of 5-hydroxytryptamine(1A) receptor concentration with multiinjection
Costes, Nicolas; Merlet, I.; Zimmer, L. et al

in Journal of Cerebral Blood Flow & Metabolism (2002), 22

The selectivity of [F-18]MPPF (fluorine-18-labeled 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been ... [more ▼]

The selectivity of [F-18]MPPF (fluorine-18-labeled 4-(2'-methoxyphenyl)-1-[2'-(N-2"-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5-hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and humans. The authors quantified the parameters of ligand-receptor exchanges using a double-injection protocol. After injection of a tracer and a coinjection dose of [F-18]MPPF, dynamic positron emission tomography (PET) data Were acquired during a 160-minute session in five healthy males. These PET and magnetic resonance imaging data were coregistered for anatomical identification. A three-compartment model was used to determine six parameters: F-v (vascular fraction). K-1, k(2) (plasma/free compartment exchange rate). k(off). k(on)/V-r (association and dissociation rate), B-max (receptor concentration), and to deduce K-d (apparent equilibrium dissociation rate). The model was fitted with regional PET kinetics and arterial input function corrected for metabolites. Analytical distribution volume and binding potential Were compared With indices generated by Logan-Patlak graphical analysis. The 5HT(1A) specificity for MPPF was evidenced. A B-max of 2.9 pmol/mL and a K-d of 2.8 nmol/L were found in hippocampal regions, K-d and distribution volume in the free compartment were regionally stable. and the Logan binding potential was linearly correlated to B-max. This study confirms the value of MPPF in the investigation of normal and pathologic systems involving the limbic network and 5-HT1A receptors. Standard values can be used for the simulation of simplified protocols. [less ▲]

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