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See detailImaging a cognitive model of apraxia: The neural substrate of gesture-specific cognitive processes
Peigneux, Philippe ULg; Van der Linden, Martial ULg; Garraux, Gaëtan ULg et al

in Human Brain Mapping (2004), 21(3), 119-142

The present study aimed to ascertain the neuroanatomical basis of an influential neuropsychological model for upper limb apraxia [Rothi LJ, et al. The Neuropsychology of Action. 1997. Hove, UK: Psychology ... [more ▼]

The present study aimed to ascertain the neuroanatomical basis of an influential neuropsychological model for upper limb apraxia [Rothi LJ, et al. The Neuropsychology of Action. 1997. Hove, UK: Psychology Press]. Regional cerebral blood flow was measured in healthy volunteers using (H2O)-O-15 PET during performance of four tasks commonly used for testing upper limb apraxia, i.e., pantomime of familiar gestures on verbal command, imitation of familiar gestures, imitation of novel gestures, and an action-semantic task that consisted in matching objects for functional use. We also re-analysed data from a previous PET study in which we investigated the neural basis. of the visual analysis of gestures. First; we found that two sets of discrete brain areas are predominantly engaged in the imitation of familiar and novel gestures, respectively. Segregated brain activation for novel gesture mutation concur with neuropsychological reports to support the hypothesis that knowledge about the organization of the human body mediates the transition from visual perception to motor execution when imitating novel gestures [Goldenberg Neuropsychologia 1995;35.63-72]. Second, conjunction analyses revealed distinctive neural bases for most of the gesture-specific cognitive processes proposed in this cognitive model of upper limb apraxia. However, a functional analysis of brain imaging data suggested that one single memory store may be used for "to be-perceived" and "to-be-produced" gestural representations, departing from Rothi et al.'s proposal. Based on the above considerations, we suggest and discuss a revised model for upper limb apraxia that might best account for both brain imaging findings and neuropsychological dissociations reported in the apraxia literature. (C) 2004 Wiley-Liss, Inc. [less ▲]

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See detailLearned material content and acquisition level modulate cerebral reactivation during posttraining rapid-eye-movements sleep
Peigneux, Philippe ULg; Laureys, Steven ULg; Fuchs, Sonia et al

in NeuroImage (2003), 20(1), 125-134

We have previously shown that several brain areas are activated both during sequence learning at wake and during subsequent rapid-eye-movements (REM) sleep (Nat. Neurosci. 3 (2000) 831-836), suggesting ... [more ▼]

We have previously shown that several brain areas are activated both during sequence learning at wake and during subsequent rapid-eye-movements (REM) sleep (Nat. Neurosci. 3 (2000) 831-836), suggesting that REM sleep participates in the reprocessing of recent memory traces in humans. However, the nature of the reprocessed information remains open. Here, we show that regional cerebral reactivation during posttraining REM sleep is not merely related to the acquisition of basic visuomotor skills during prior practice of the serial reaction time task, but rather to the implicit acquisition of the probabilistic rules that defined stimulus sequences. Moreover, functional connections between the reactivated cuneus and the striatum-the latter being critical for implicit sequence learning-are reinforced during REM sleep after practice on a probabilistic rather than on a random sequence of stimuli. Our results therefore support the hypothesis that REM sleep is deeply involved in the reprocessing and optimization of the high-order information contained in the material to be learned. In addition, we show that the level of acquisition of probabilistic rules attained prior to sleep is correlated to the increase in regional cerebral blood flow during subsequent REM sleep. This suggests that posttraining cerebral reactivation is modulated by the strength of the memory traces developed during the learning episode. Our data provide the first experimental evidence for a link between behavioral performance and cerebral reactivation during REM sleep. (C) 2003 Elsevier Inc. All rights reserved. [less ▲]

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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 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 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 detailInfluence of P-glycoprotein on the tissue distribution in rats of the 5-HT1A antagonist p-[18F]MPPF.
Plenevaux, Alain ULg; Lacan, G.; Defraiteur, C. et al

in Society for Neuroscience / Abstracts (2002)

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See detailFast F-18 FDG synthesis by alkaline hydrolysis on a low polarity solid phase supports
Lemaire, Christian ULg; Damhaut, P.; Lauricella, Benjamino ULg et al

in Journal of Labelled Compounds & Radiopharmaceuticals (2002), 45(5), 435-447

The synthesis of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) has been simplified by the use of a tC18 Sep Pak cartridge to effect purification and hydrolysis of the tetraacetylated [18F]fluoro-glucose ... [more ▼]

The synthesis of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) has been simplified by the use of a tC18 Sep Pak cartridge to effect purification and hydrolysis of the tetraacetylated [18F]fluoro-glucose compound ([18F]TAG). After radiolabelling, this derivative was trapped on a solid phase extraction (SPE) cartridge and the residual reaction solvent (CH3CN), reagents (K222, K2CO3,) and by-products removed by washing the support with water. After this cleaning step, the acetyl groups were cleaved on the same tC18 column using 2N sodium hydroxide. This fast reaction proceeded near quantitatively (>98%) at room temperature in less than 2 min. The [18F]FDG was then recovered with a small amount of water, neutralized with a slight excess of 2N hydrochloric acid, buffered for pH with a citrate solution and finally purified on a neutral alumina oxide and a second tC18 column. After filtration, the radiochemical yield of this [18F]FDG isotonic solution after more than 100 production runs was found to be very reliable and reproducible (70±6% decay corrected). The synthesis time was about 22 min. Quality controls showed that the radiochemical purity was higher than 98% and in any case no [18F]FDM was detected. Only traces of 2-chloro-2-deoxy-glucose (ClDG) were found in the final sample (64±9 g/ batch of 16 ml). [18F]FDG specific activity averaged between 1 and 20 Ci/µmol (EOS). No evaporation and use of ion retardation resin (AG11A8) are required. Moreover, this new approach is suitable for complete remote operation using available single use medical components. Copyright © 2002 John Wiley [less ▲]

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See detailGeneration of rapid eye movements during paradoxical sleep in humans
Peigneux, Philippe ULg; Laureys, Steven ULg; Fuchs, Sonia et al

in NeuroImage (2001), 14(3), 701-708

Although rapid eye movements (REMs) are a prominent feature of paradoxical sleep (PS), their origin and functional significance remain poorly understood in humans. In animals, including nonhuman primates ... [more ▼]

Although rapid eye movements (REMs) are a prominent feature of paradoxical sleep (PS), their origin and functional significance remain poorly understood in humans. In animals, including nonhuman primates, REMs during PS are closely related to the occurrence of the so-called PGO waves, i.e., prominent phasic activities recorded throughout the brain but predominantly and most easily in the pons (P), the lateral geniculate bodies (G), and the occipital cortex (O). Therefore, and because the evolution of species is parsimonious, a plausible hypothesis would be that during PS in humans, REMs are generated by mechanisms similar to PGO waves. Using positron emission tomography and iterative cerebral blood flow measurements by H(2)(15)O infusions, we predicted that the brain regions where the PGO waves are the most easily recorded in animals would be differentially more active in PS than in wakefulness, in relation with the density of the REM production [i.e., we looked for the condition (PS versus wakefulness) by performance (REM density) interaction]. Accordingly, we found a significant interaction effect in the right geniculate body and in the primary occipital cortex. The result supports the hypothesis of the existence of processes similar to PGO waves in humans, responsible for REM generation. The interest in the presence of PGO waves in humans is outstanding because the cellular processes involved in, or triggered by, PGO waves might favor brain plasticity during PS. [less ▲]

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See detailExperience-dependent changes in cerebral functional connectivity during human rapid eye movement sleep
Laureys, Steven ULg; Peigneux, Philippe ULg; Phillips, Christophe ULg et al

in Neuroscience (2001), 105(3), 521-525

One function of sleep is hypothesized to be the reprocessing and consolidation of memory traces (Smith, 1995; Gais et al., 2000; McGaugh, 2000; Stickgold et al., 2000). At the cellular level, neuronal ... [more ▼]

One function of sleep is hypothesized to be the reprocessing and consolidation of memory traces (Smith, 1995; Gais et al., 2000; McGaugh, 2000; Stickgold et al., 2000). At the cellular level, neuronal reactivations during post-training sleep in animals have been observed in hippocampal (Wilson and McNaughton, 1994) and cortical (Amzica et al., 1997) neuronal populations. At the systems level, using positron emission tomography, we have recently shown that some brain areas reactivated during rapid-eye-movement sleep in human subjects previously trained on an implicit learning task (a serial reaction time task) (Maquet et al., 2000). These cortical reactivations, located in the left premotor area and bilateral cuneus, were thought to reflect the reprocessing - possibly the consolidation - of memory traces during post-training rapid-eye-movement sleep. Here, the experience-dependent functional connectivity of these brain regions is examined. It is shown that the left premotor cortex is functionally more correlated with the left posterior parietal cortex and bilateral pre-supplementary motor area during rapid-eye-movement sleep of subjects previously trained to the reaction time task compared to rapid-eye-movement sleep of untrained subjects. The increase in functional connectivity during post-training rapid-eye-movement sleep suggests that the brain areas reactivated during post-training rapid-eye-movement sleep participate in the optimization of the network that subtends subject's visuo-motor response. The optimization of this visuo-motor network during sleep could explain the gain in performance observed during the following day. [less ▲]

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See detailEtudes par tomographie à émission de positons chez des patients en coma, en état végétatif ou de conscience minimale, en «locked-in syndrome» et en mort cérébrale
Laureys, Steven ULg; Faymonville, Marie-Elisabeth ULg; Berre, Jacques et al

in L'évaluation neurophysiologique des comas, de la mort encéphalique et des états végétatifs (2001)

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See detailStriatum forever, despite sequence learning variability : A random effect analysis of PET data
Peigneux, Philippe ULg; Maquet, Pierre ULg; Meulemans, Thierry ULg et al

in Human Brain Mapping (2000), 10(4), 179-194

This PET study is concerned with the what, where, and how of implicit sequence learning. In contrast with previous studies imaging the serial reaction time (SRT) task, the sequence of successive locations ... [more ▼]

This PET study is concerned with the what, where, and how of implicit sequence learning. In contrast with previous studies imaging the serial reaction time (SRT) task, the sequence of successive locations was determined by a probabilistic finite-state grammar. The implicit acquisition of statistical relationships between serially ordered elements (i.e., what) was studied scan by scan, aiming to evidence the brain areas (i.e., where) specifically involved in the implicit processing of this core component of sequential higher-order knowledge. As behavioural results demonstrate between- and within-subjects variability in the implicit acquisition of sequential knowledge through practice, functional PET data were modelled using a random-effect model analysis (i.e., how) to account for both sources of behavioural variability. First, two mean condition images were created per subject depending on the presence or not of implicit sequential knowledge at the time of each of the 12 scans. Next, direct comparison of these mean condition images provided the brain areas involved in sequential knowledge processing. Using this approach, we have shown that the striatum is involved in more than simple pairwise associations and that it has the capacity to process higher-order knowledge. We suggest that the striatum is not only involved in the implicit automatization of serial information through prefrontal cortex-caudate nucleus networks, but also that it plays a significant role for the selection of the most appropriate responses in the context created by both the current and previous stimuli, thus contributing to better efficiency and faster response preparation in the SRT task. Hum. Brain Mapping 10:179-194, 2000. © 2000 Wiley-Liss, Inc. [less ▲]

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See detailExperience-dependent changes in cerebral activation during human REM sleep
Maquet, Pierre ULg; Laureys, Steven ULg; Peigneux, Philippe ULg et al

in Nature Neuroscience (2000), 3(8), 831-836

The function of rapid-eye-movement (REM) sleep is stiil unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET ... [more ▼]

The function of rapid-eye-movement (REM) sleep is stiil unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET) and regional cerebral blood flow measurements, we show that waking experience influences regional brain activity during subsequent sleep. Several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously trained on the task than in non-trained subjects. These results support the hypothesis that memory traces are processed during REM sleep in humans. [less ▲]

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See detail[(18)F]p-MPPF: A radiolabeled antagonist for the study of 5-HT(1A) receptors with PET
Plenevaux, Alain ULg; Lemaire, Christian ULg; Aerts, Joël ULg et al

in Nuclear Medicine & Biology (2000), 27(5), 467-71

This paper summarizes the present status of the researches conducted with [(18)F]4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido ]ethyl]-piperazine known as [(18)F]p-MPPF, a new 5-HT(1A ... [more ▼]

This paper summarizes the present status of the researches conducted with [(18)F]4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-fluorobenzamido ]ethyl]-piperazine known as [(18)F]p-MPPF, a new 5-HT(1A) antagonist for the study of the serotonergic neurotransmission with positron emission tomography (PET). This includes chemistry, radiochemistry, animal data (rats, cats, and monkeys) with autoradiography and PET, human data with PET, toxicity, and metabolism. [less ▲]

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See detailImpaired cerebral connectivity in vegetative state
Laureys, Steven ULg; Faymonville, Marie ULg; Goldman, S. et al

in Physiological imaging of the brain with PET (2000)

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See detailBrain activation during somatosensory and auditory stimulation in acute vegetative state of anoxic origin
Laureys, Steven ULg; Faymonville, Marie ULg; Del Fiore, G. et al

in Physiological imaging of the brain with PET (2000)

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See detailThe role of lateral occipitotemporal junction and area MT/V5 in the visual analysis of upper-limb postures
Peigneux, Philippe ULg; Salmon, Eric ULg; Van der Linden, Martial ULg et al

in Neuroimage (2000), 11(6), 644-655

Humans, like numerous other species, strongly rely on the observation of gestures of other individuals in their everyday life. It is hypothesized that the visual processing of human gestures is sustained ... [more ▼]

Humans, like numerous other species, strongly rely on the observation of gestures of other individuals in their everyday life. It is hypothesized that the visual processing of human gestures is sustained by a specific functional architecture, even at an early prelexical cognitive stage, different from that required for the processing of other visual entities. In the present PET study, the neural basis of visual gesture analysis was investigated with functional neuroimaging of brain activity during naming and orientation tasks performed on pictures of either static gestures (upper-limb postures) or tridimensional objects. To prevent automatic object-related cerebral activation during the visual processing of postures, only intransitive postures were selected, i.e., symbolic or meaningless postures which do not imply the handling of objects. Conversely, only intransitive objects which cannot be handled were selected to prevent gesture-related activation during their visual processing. Results clearly demonstrate a significant functional segregation between the processing of static intransitive postures and the processing of intransitive tridimensional objects. Visual processing of objects elicited mainly occipital and fusiform gyrus activity, while visual processing of postures strongly activated the lateral occipitotemporal junction, encroaching upon area MT/V5, involved in motion analysis. These findings suggest that the lateral occipitotemporal junction, working in association with area MT/V5, plays a prominent role in the high-level perceptual analysis of gesture, namely the construction of its visual representation, available for subsequent recognition or imitation. (C) 2000 Academic Press. [less ▲]

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See detailAuditory processing in the vegetative state.
Laureys, Steven ULg; Faymonville, Marie ULg; Degueldre, Christian ULg et al

in Brain : A Journal of Neurology (2000), 123 ( Pt 8)

H(2)(15)O-PET was used to investigate changes in regional cerebral blood flow in response to auditory stimulation in patients in the vegetative state. Five patients in a vegetative state of hypoxic origin ... [more ▼]

H(2)(15)O-PET was used to investigate changes in regional cerebral blood flow in response to auditory stimulation in patients in the vegetative state. Five patients in a vegetative state of hypoxic origin were compared with 18 age-matched controls. In addition, the cerebral metabolism of these patients and 53 age-matched controls was studied using [(18)F]fluorodeoxyglucose. In control subjects, auditory click stimuli activated bilateral auditory cortices [Brodmann areas (BA) 41 and 42] and the contralateral auditory association cortices (BA 22). In the patients, although resting metabolism was decreased to 61% of normal values, bilateral auditory areas 41 and 42 showed activation as seen in the controls, but the temporoparietal junction cortex (BA 22) failed to be activated. Moreover, the auditory association cortex was functionally disconnected from the posterior parietal association area (BA 40), the anterior cingulate cortex (BA 24) and the hippocampus, as revealed by psychophysiological interaction analysis. Thus, despite altered resting metabolism, the auditory primary cortices were still activated during external stimulation, whereas hierarchically higher-order multi- modal association areas were not. Such a cascade of functional disconnections along the auditory cortical pathways, from the primary auditory areas to multimodal and limbic areas, suggests that the residual cortical processing observed in the vegetative state cannot lead to the integrative processes that are thought to be necessary for the attainment of the normal level of awareness. [less ▲]

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See detailTissue distribution, autoradiography, and metabolism of 4-(2'-methoxyphenyl)-1-[2' -[N-2"-pyridinyl)-p-[(18)F]fluorobenzamido]ethyl]piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist for positron emission tomography: An In vivo study in rats.
Plenevaux, Alain ULg; Weissmann, D.; Aerts, Joël ULg et al

in Journal of Neurochemistry (2000), 75(2), 803-11

The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-[(18)F]fluorobenzamido ]ethyl]-piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist, was studied in awake, freely moving ... [more ▼]

The in vivo behavior of 4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-p-[(18)F]fluorobenzamido ]ethyl]-piperazine (p-[(18)F]MPPF), a new serotonin 5-HT(1A) antagonist, was studied in awake, freely moving rats. Biodistribution studies showed that the carbon-fluorine bond was stable in vivo, that this compound was able to cross the blood-brain barrier, and that a general diffusion equilibrium could account for the availability of the tracer. The great quantity of highly polar metabolites found in plasma did not contribute to the small amounts of metabolites found in hippocampus, frontal cortex, and cerebellum. Exvivo p-[(18)F]MPPF and in vitro 8-hydroxy-2-(di-n-[(3)H]propylamino)tetralin autoradiography were compared both qualitatively and quantitatively. Qualitative evaluation proved that the same brain regions were labeled and that the p-[(18)F]MPPF labeling is (a) in total agreement with the known distribution of 5-HT(1A) receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in vivo labeling pattern obtained with p-[(18)F]MPPF cannot be explained by differences in regional blood flow, capillary density, or permeability. The 5-HT(1A) specificity of p-[(18)F]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to evaluate parameters characterizing 5-HT(1A) binding sites in the brain. [less ▲]

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See detailImpaired effective cortical connectivity in vegetative state : Preliminary investigation using PET
Laureys, Steven ULg; Goldman, Serge; Phillips, Christophe ULg et al

in Neuroimage (1999), 9(4), 377-382

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural ... [more ▼]

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural networks. Our hypothesis was that part of the neural correlate underlying VS is an altered connectivity, especially between the associative cortices. We assessed regional cerebral glucose metabolism (rCMRGlu) and effective cortical connectivity in four patients in VS by means of statistical parametric mapping and [F-18]fluorodeoxyglucose-positron emission tomography. Our data showed a common pattern of impaired rCMRGlu in the prefrontal, premotor, and parietotemporal association areas and posterior cingulate cortex/precuneus in VS. In a next step, we demonstrated that in VS patients various prefrontal and premotor areas have in common that they are less tightly connected with the posterior cingulate cortex than in normal controls. These results provide a strong argument for an alteration of cortical connectivity in VS patients. (C) 1999 Academic Press. [less ▲]

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