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ABSTRACT: BACKGROUND: Brain areas involved in nociception have been repeatedly investigated. Therefore, brain responses to physiological pain conditions are well identified. The same is not true for allodynic pain in patients with neuropathic pain since the cortical reorganizations that are involved in the conversion of non-noxious stimuli into painful sensations still remain unknown. METHODS: The present positron emission tomography (PET) study enrolled 19 patients with dynamic mechanical allodynia to brushing or to cold rubbing of the skin. PET activations during allodynic stimulation were compared to those obtained with the same innocuous stimulation applied outside the neuropathic pain area (control). In a second comparison, they were compared with responses to a noxious heat stimulation applied outside the neuropathic pain area (experimental pain). RESULTS: Common responses to allodynia and control stimulations were found in contralateral SI, SII and insula and in ipsilateral cerebellum. Not surprisingly, heat pain condition was associated with activations in contralateral prefrontal and SII cortices and, bilaterally, in the anterior insular cortices. Distinctive cortical responses between control and allodynic conditions were restricted to one activation within the contralateral anterior insula, a region also activated by experimental heat pain. CONCLUSIONS: The insular subdivision was inappropriately activated considering the innocuous nature of the stimulus, but adequately activated with regard to pain-evoked sensation. Subcortically, the hypothesis of reorganization at any level of the somatosensory and pain pathways underlying such insular activity was supported by the observed shift of thalamic activation from a lateral-posterior to an anterior-medial position.
European journal of pain (London, England) 03/2013; · 3.37 Impact Factor
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ABSTRACT: To date, two positron emission tomography (PET) studies have explored 5-HT(1A) receptor density in the hippocampus of Alzheimer's disease (AD) patients. They showed early changes of 5-HT(1A) receptors in this brain region, known to have a dense serotonergic innervation. These studies only reported measurements in hippocampus. In the present PET study, we used an antagonist of 5-HT(1A) receptors, the [(18)F]MPPF (1) to explore 5-HT(1A) receptor density in the whole brain of AD patients at a mild stage of dementia and amnestic mild cognitive impairment (aMCI) patients compared to a control population; (2) to explore more precisely the 5-HT(1A) receptor density in the limbic brain regions of AD patients and aMCI patients compared to controls. Voxel-based analyses were performed to assess differences in the [(18)F]MPPF binding potential (BP) between AD patients and aMCI patients compared to controls. Analyses of whole-brain [(18)F]MPPF BP showed a global decrease in AD brains in contrast with a global increase in aMCI brains. In AD brains, a significant decrease of BP was detected in hippocampus and parahippocampal gyrus, whereas a significant increase of BP was observed in the inferior occipital gyrus in aMCI brains. These whole brain results are in accordance to hippocampal data reported in a previous study, showing an increase of [(18)F]MPPF binding in the aMCI group contrasting with a decrease in the AD group. Altogether, these results suggest the implication of a compensatory mechanism illustrated by an up regulation of serotonergic metabolism at the aMCI stage before a breakdown of this mechanism at the AD stage. This difference of serotonergic receptor labeling allows to distinguish the groups of aMCI patients from mild AD patients with specific [(18)F]MPPF PET profiles for each patient group.
NeuroImage 05/2008; 40(3):1251-6. · 5.89 Impact Factor
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L Truchot,
S N Costes,
L Zimmer,
B Laurent, D Le Bars,
C Thomas-Antérion,
B Croisile,
B Mercier,
M Hermier,
A Vighetto,
P Krolak-Salmon
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ABSTRACT: Recent studies have suggested modifications of serotonin cerebral metabolism and of 5-HT(1A) receptors density in Alzheimer disease (AD). This study aims at exploring hippocampus 5-HT(1A) receptor density in patients at the amnesic mild cognitive impairment (aMCI) and mild AD dementia stages.
With use of PET with a selective 5-HT(1A) antagonist, 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro-benzamidoethylpiperazine ([(18)F]MPPF), the hippocampus 5-HT(1A) binding potential (BP) was quantified in 10 patients with mild AD, in 11 patients with aMCI, and in 21 aged paired control subjects. To take into account hippocampal atrophy, a partial volume correction was applied to the [(18)F]MPPF data, leading to the calculation of a corrected BP (BP(c)). Comparison of hippocampus BP over populations was performed using Kruskal-Wallis rank analysis.
Hippocampus serotonergic receptor binding distinguishes patients from controls and patients with aMCI from patients with AD. In aMCI patients, the mean hippocampus BP(c) was 59% higher than the controls' (p < 0.005), and it was conversely 35% lower in patients with mild AD (p < 0.01). The difference in BP(c) values between patients with aMCI and mild AD was large, resulting in a p value of <0.0005. These differences were not related to hippocampus atrophy.
A compensatory mechanism illustrated by an up-regulation of serotonergic metabolism has been shown at the stage of amnesic mild cognitive impairment (aMCI) in contrast with a dramatic decrease at later stages of Alzheimer disease (AD). This difference of hippocampus serotonergic receptor labeling allows distinguishing of patients with aMCI from those with mild AD. Exploring 5-HT(1A) receptors with 2'-methoxyphenyl-(N-2'-pyridinyl)-p-(18)F-fluoro-benzamidoethylpiperazine PET seems to be of interest for better understanding pathophysiologic changes at early stages of AD.
Neurology 09/2007; 69(10):1012-7. · 8.31 Impact Factor
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ABSTRACT: Brain tumours responsible for longstanding partial epilepsy are characterised by a high prevalence of dysembryoplastic neuroepithelial tumour (DNT), whose natural evolution is much more benign than that of gliomas. The preoperative diagnosis of DNT, which is not yet feasible on the basis of available clinical and imaging data, would help optimise the therapeutic strategy for this type of tumour. This study tested whether [(11)C]-methionine positron emission tomography (MET-PET) could help to distinguish DNTs from other epileptogenic brain tumours.
Prospective study of 27 patients with partial epilepsy of at least six months duration related to a non-rapidly progressing brain tumour on magnetic resonance imaging (MRI). A structured visual analysis, which distinguished between normal, moderately abnormal, or markedly abnormal tumour methionine uptake, as well as various regions of interest and semiquantitative measurements were conducted.
Pathological results showed 11 DNTs (41%), 5 gangliogliomas (18%), and 11 gliomas (41%). MET-PET visual findings significantly differed between the various tumour types (p<0.0002), regardless of gadolinium enhancement on MRI, and were confirmed by semiquantitative analysis (p<0.001 for all calculated ratios). All gliomas and gangliogliomas were associated with moderately or markedly increased tumour methionine uptake, whereas 7/11 DNTs had a normal methionine uptake, including all six located in the mesiotemporal structures. No DNT presented with a marked MET-PET abnormality.
Normal MET-PET findings in patient with an epileptogenic and non-rapidly progressing brain tumour are suggestive of DNT, whereas a markedly increased tumour methionine uptake makes this diagnosis unlikely.
Journal of Neurology Neurosurgery & Psychiatry 12/2005; 76(12):1686-92. · 4.76 Impact Factor
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ABSTRACT: Enhancing cerebral serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is a common property of antidepressant treatments and the basis for their efficacy. 5-HT1A receptors located on the cell body and dendrites of 5-HT neurons (autoreceptors) play a key role in this regard. Because they normally mediate an inhibition of neuronal firing, their desensitization is a prerequisite to the delayed enhancement of 5-HT neurotransmission upon treatment with monoamine oxidase (MAOI) inhibitors or specific serotonin reuptake inhibitors (SSRI). Using beta-sensitive microprobes in vivo, we measured a significant decrease (-30%) in binding sites for the 5-HT1A PET radioligand [18F]MPPF associated with an equivalent reduction (-34%) in the cell surface density of 5-HT1A receptor immunoreactivity (internalization), in the nucleus raphe dorsalis (autoreceptors), but not hippocampus (heteroreceptors), of rats given a single dose of the specific 5-HT1A receptor agonist, 8-OH-DPAT (0.5 mg/kg, iv). This effect was completely blocked by pretreatment with the selective 5-HT1A antagonist WAY 100635. Having ruled out that this decreased density of [18F]MPPF binding in the nucleus raphe dorsalis of 8-OH-DPAT-treated rats resulted from a local blood flow effect, we obtained autoradiographic evidence indicating that the total amount of specific binding of [18F]MPPF in tissue sections was unaffected by the 8-OH-DPAT treatment in either NRD or hippocampus. It was therefore concluded that the internalization of 5-HT1A autoreceptors accounted for the decreased binding in vivo of [18F]MPPF in the nucleus raphe dorsalis of rats treated with 8-OH-DPAT. Thus, PET imaging might provide a mean to measure 5-HT1A receptor internalization in human brain and thus assess responsiveness to antidepressant treatment.
NeuroImage 08/2004; 22(3):1421-6. · 5.89 Impact Factor
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ABSTRACT: Whether the intrinsic epileptogenicity of hypothalamic hamartomas (HH) is responsible for the entire clinical spectrum of epileptic, neuropsychological and behavioural disorders associated with HH, remains an open issue, in as much as morphologically similar HH can be associated with dramatically different seizure types and cognitive outcomes. The aim of this study was to investigate brain glucose metabolism in patients with epileptogenic HH, in an attempt to identify signs of focal cortical and subcortical dysfunction which might correlate with other clinical data. We have studied five patients with epileptogenic HH using [18F]-fluoro-desoxyglucose and positron emission tomography (FDG-PET). All our patients also underwent an optimal MRI and a video-EEG monitoring, as well as an intra-cranial EEG recording in one of them. The anatomical distribution of FDG-PET abnormalities was compared to that of interictal and ictal electroclinical findings. All five patients demonstrated focal hypometabolism, ipsilateral to the predominant EEG abnormalities and side of HH. Hypometabolic areas greatly varied between patients, but were grossly concordant with the cortical regions suspected to participate in the ictal discharges in each individual. Epileptogenic hypothalamic hamartomas are usually associated with focal cortical hypometabolism in regions which might participate in the overall HH-driven epileptic network. Whether these cortical abnormalities only reflect the propagation of ictal discharges, or a potentially independent seizure onset zone remains unknown.
Epileptic disorders: international epilepsy journal with videotape 01/2004; 5(4):219-27. · 1.50 Impact Factor
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ABSTRACT: Subthalamic nucleus (STN) stimulation mechanism of action remains a matter for debate. In animals, an increased striatal dopamine (DA) release due to STN stimulation has been reported.
To determine in Parkinson's disease (PD) patients using positron emission tomography (PET) and [11C]-Raclopride, whether STN stimulation induces a striatal DA release.
Nine PD patients with bilateral STN stimulation were enrolled and underwent two [11C]-Raclopride PET scans. The scans were randomly performed in off and on stimulation conditions. Striatal [11C]-Raclopride binding potential (BP) was calculated using regions of interest and statistical parametric mapping.
For PD patients, the mean [(11C]-Raclopride BP (+/- SD) were, in Off stimulation condition: 1.7 +/- 0.3 for the right caudate nucleus, 1.8 +/- 0.4 for the left caudate nucleus, 2.6 +/- 0.5 for the right putamenand 2.6 +/- 0.5 for the left putamen. In On stimulation condition: 1.7 +/- 0.4 for the right caudate nucleus, 1.9 +/- 0.5 for the left caudate nucleus, 2.8 +/- 0.7 for the right putamen and 2.7 +/- 0.8 for the left putamen. No significant difference of BP related to the stimulation was noted.
STN stimulation does not produce significant variations of striatal DA release as assessed by PET and [11C]-Raclopride.
Journal of Neurology 11/2003; 250(10):1219-23. · 3.47 Impact Factor
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ABSTRACT: The aim of this study was to demonstrate the ability of a recently developed beta(+)-range sensitive intracerebral probe (beta-Microprobe) to measure the binding kinetics of [(18)F]MPPF, a well-documented 5-HT(1A) serotoninergic receptor ligand, in the dorsal raphe nucleus (DRN) of the anaesthetised rat. This midbrain nucleus presents a high concentration of 5-HT(1A) receptors known to be implicated in the effects of antidepressants. The difficulty confronting this study lay in the fact that the dimensions of the DRN are smaller than the detection volume of the beta-Microprobe. In the first part of the study, we studied the feasibility of this measurement from a theoretical point of view by autoradiography and a Monte Carlo simulation. We determined the optimal beta-Microprobe location close to the DRN and verified that this configuration allowed accurate determination of [(18)F]MPPF specific binding in the nucleus. In the second part of our study, we measured the in vivo time-concentration curves of [(18)F]MPPF binding in the DRN in comparison with the cerebellum. The specificity of [(18)F]MPPF binding in the DRN was confirmed by its displacement after non-labelled 5-HT(1A)antagonist injection (MPPF or WAY-100635). Moreover, we verified the feasibility of using beta-Microprobe monitoring and simultaneous validation by microdialysis to study the effect of an increase in extracellular serotonin, induced by fenfluramine injection, on [(18)F]MPPF binding in the DRN. Our theoretical simulations, confirmed by our experimental results, demonstrate the ability of this new device to monitor in vivo the binding of [(18)F]MPPF in the DRN of anaesthetised rodents.
European journal of nuclear medicine and molecular imaging 10/2002; 29(9):1237-47. · 4.99 Impact Factor
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ABSTRACT: The in vivo behavior of 4-(2′-methoxyphenyl)-1-[2′-[N-(2″-pyridinyl)-p-[18F]fluorobenzamido]ethyl]-piperazine (p-[18F]MPPF), a new serotonin 5-HT1A 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-[18F]MPPF and in vitro 8-hydroxy-2-(di-n-[3H]propylamino)tetralin autoradiography were compared both qualitatively and quantitatively. Qualitative evaluation proved that the same brain regions were labeled and that the p-[18F]MPPF labeling is (a) in total agreement with the known distribution of 5-HT1A receptors in rats and (b) characterized by very low nonspecific binding. Quantitative comparison demonstrated that the in vivo labeling pattern obtained with p-[18F]MPPF cannot be explained by differences in regional blood flow, capillary density, or permeability. The 5-HT1A specificity of p-[18F]MPPF and binding reversibility were confirmed in vivo with displacement experiments. Thus, this compound can be used to evaluate parameters characterizing 5-HT1A binding sites in the brain.
Journal of Neurochemistry 01/2002; 75(2):803 - 811. · 4.06 Impact Factor
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ABSTRACT: Despite its critical sociobiological importance, the brain processing of visual sexual stimuli has not been characterized precisely in human beings. We used Positron Emission Tomography (PET) to investigate responses of regional cerebral blood flow (rCBF) in nine healthy males presented with visual sexual stimuli of graded intensity. Statistical Parametric Mapping was used to locate brain regions whose activation was associated with the presentation of the sexual stimuli and was correlated with markers of sexual arousal. The claustrum, a region whose function had been unclear, displayed one of the highest activations. Additionally, activations were recorded in paralimbic areas (anterior cingulate gyrus, orbito-frontal cortex), in the striatum (head of caudate nucleus, putamen), and in the posterior hypothalamus. By contrast, decreased rCBF was observed in several temporal areas. Based on these results, we propose a model of the brain processes mediating the cognitive, emotional, motivational, and autonomic components of human male sexual arousal.
Human Brain Mapping 12/2000; 11(3):162-77. · 5.88 Impact Factor
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ABSTRACT: 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.
Journal of Neurochemistry 09/2000; 75(2):803-11. · 4.06 Impact Factor
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A Plenevaux,
C Lemaire,
J Aerts,
G Lacan,
D Rubins,
W P Melega,
C Brihaye,
C Degueldre,
S Fuchs,
E Salmon,
P Maquet,
S Laureys,
P Damhaut,
D Weissmann, D Le Bars,
J F Pujol,
A Luxen
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ABSTRACT: 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.
Nuclear Medicine and Biology 08/2000; 27(5):467-71. · 3.02 Impact Factor
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ABSTRACT: Only few noninvasive methods have the potential to quantitate renal blood flow (RBF) in humans. Positron emission tomography (PET) is a clinical imaging method that can be used to measure the tissue blood flow noninvasively. The purpose of this study was to validate PET measurement of RBF using 15O-labeled water (H215O), a tracer that allows repeated measurements at short time intervals.
RBF was measured in six pigs by PET and by radioactive microspheres (MS). Three measurements were performed in each pig at baseline (BL), during vascular expansion and dopamine infusion (DA; 20 microg. kg-1. min-1 intravenously), and during angiotensin II (Ang II) infusion (50 ng. kg-1. min-1 intravenously). RBF was estimated from aortic and renal tracer kinetics using a model adapted from the blood flow model described by Kety and Smith.
PET and MS values correlated strongly (y = 0.79x + 42, r = 0.93, P < 0.0001) over the RBF range from 100 to 500 mL. min-1. 100 g-1. Pharmacologically induced changes were significant and were measured equally well by PET and MS: 38 and 39%, respectively, below BL (P < 0.005 and P < 0.05) under Ang II, and 47 and 48%, respectively, above BL (P < 0.005 and P < 0.01) under DA. A Bland and Altman representation showed a low average difference of -17 +/- 45 mL. min-1. 100 g-1 (mean +/- SD).
To our knowledge, this study provides the first validation of RBF measurement by PET using H215O over a large range of RBF values (100 to 500 mL. min-1. 100 g-1), which correspond to RBF values in both healthy subjects and in patients suffering from chronic renal failure.
Kidney International 07/2000; 57(6):2511-8. · 6.61 Impact Factor
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ABSTRACT: The in vivo and ex vivo distributions and the pharmacological profile of the fluorinated phenylpiperazine derivative p-[(18)F]MPPF (4-(2'-methoxyphenyl)-1-[2'-(N-2"-pyridinyl)-p-fluorobenzamido]-et hyl piperazine) were evaluated in the cat brain as a potential selective antagonist for 5-HT(1A) receptors using PET. After intravenous injection of p-[(18)F]MPPF in cats, there was a rapid accumulation of radioactivity in the brain, with 4% of the total radioactivity injected present in the brain at 4 minutes postinjection. The highest uptakes of radioactivity were observed in the hippocampus and cingulate cortex, regions known to be rich in 5-HT(1A) receptors, whereas lower levels of radioactivity were observed in the cerebellum. The mean ratio of radioactivity in the hippocampus to the cerebellum was 4.29 (SD = 0.21; n = 5) from 40 to 90 minutes postinjection of p-[(18)F]MPPF. The corresponding ratio for the cingulate cortex was 3.01 (SD = 0.16; n = 5). Specific binding in the hippocampus and the cingulate cortex was markedly reduced following injection of unlabeled WAY-100635 and pindolol but was unaffected by treatment with alpha1, 5-HT(2), or reuptake inhibitor agents indicating reversibility and selectivity of p-[(18)F]MPPF binding to 5-HT(1A) receptors. Ex vivo autoradiographic study with p-[(18)F]MPPF in cat brain sections showed labeling of areas rich in 5-HT(1A) receptors with a regional brain distribution that closely matched that observed using PET. These results indicate that p-[(18)F]MPPF may be a useful candidate for noninvasive PET imaging of 5-HT(1A) receptors in the living human brain.
Synapse 04/2000; 35(3):192-200. · 2.94 Impact Factor
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ABSTRACT: We have observed a falsely lateralizing mesial temporal [11C]-flumazenil binding asymmetry in three patients who had temporal lobe epilepsy (TLE) with normal hippocampal volumes. This abnormality was not detected 3 months later in two of the patients who underwent a second PET study. We conclude that transient and falsely lateralizing changes of flumazenil binding might occur in patients with TLE and no hippocampal sclerosis.
Neurology 12/1999; 53(8):1882-5. · 8.31 Impact Factor
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Movement Disorders 12/1999; 14(6):1025-30. · 4.51 Impact Factor
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ABSTRACT: Although electrical stimulation of the precentral gyrus (MCS) is emerging as a promising technique for pain control, its mechanisms of action remain obscure, and its application largely empirical. Using positron emission tomography (PET) we studied regional changes in cerebral flood flow (rCBF) in 10 patients undergoing motor cortex stimulation for pain control, seven of whom also underwent somatosensory evoked potentials and nociceptive spinal reflex recordings. The most significant MCS-related increase in rCBF concerned the ventral-lateral thalamus, probably reflecting cortico-thalamic connections from motor areas. CBF increases were also observed in medial thalamus, anterior cingulate/orbitofrontal cortex, anterior insula and upper brainstem; conversely, no significant CBF changes appeared in motor areas beneath the stimulating electrode. Somatosensory evoked potentials from SI remained stable during MCS, and no rCBF changes were observed in somatosensory cortex during the procedure. Our results suggest that descending axons, rather than apical dendrites, are primarily activated by MCS, and highlight the thalamus as the key structure mediating functional MCS effects. A model of MCS action is proposed, whereby activation of thalamic nuclei directly connected with motor and premotor cortices would entail a cascade of synaptic events in pain-related structures receiving afferents from these nuclei, including the medial thalamus, anterior cingulate and upper brainstem. MCS could influence the affective-emotional component of chronic pain by way of cingulate/orbitofrontal activation, and lead to descending inhibition of pain impulses by activation of the brainstem, also suggested by attenuation of spinal flexion reflexes. In contrast, the hypothesis of somatosensory cortex activation by MCS could not be confirmed by our results.
Pain 12/1999; 83(2):259-73. · 5.78 Impact Factor
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S Stoléru,
M C Grégoire,
D Gérard,
J Decety,
E Lafarge,
L Cinotti,
F Lavenne, D Le Bars,
E Vernet-Maury,
H Rada,
C Collet,
B Mazoyer,
M G Forest,
F Magnin,
A Spira,
D Comar
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ABSTRACT: Brain areas activated in human male sexual behavior have not been characterized precisely. For the first time, positron emission tomography (PET) was used to identify the brain areas activated in healthy males experiencing visually evoked sexual arousal. Eight male subjects underwent six measurements of regional brain activity following the administration of [15O]H2O as they viewed three categories of film clips: sexually explicit clips, emotionally neutral control clips, and humorous control clips inducing positive but nonsexual emotions. Statistical Parametric Mapping was used to identify brain regions demonstrating an increased activity associated with the sexual response to the visual stimulus. Visually evoked sexual arousal was characterized by a threefold pattern of activation: the bilateral activation of the inferior temporal cortex, a visual association area; the activation of the right insula and right inferior frontal cortex, which are two paralimbic areas relating highly processed sensory information with motivational states; and the activation of the left anterior cingulate cortex, another paralimbic area known to control autonomic and neuroendocrine functions. Activation of some of these areas was positively correlated with plasma testosterone levels. Although this study should be considered preliminary, it identified brain regions whose activation was correlated with visually evoked sexual arousal in males.
Archives of Sexual Behavior 03/1999; 28(1):1-21. · 3.53 Impact Factor
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ABSTRACT: Solid phase extraction (SPE) was used for the formulation of several radiopharmaceuticals. The method involves dilution of the previously purified HPLC compound with water, trapping of the activity on an SPE bed, washing off the support, elution of the radiopharmaceutical with a small volume of ethanol (<1 mL) and dilution with sterile isotonic saline solution. Recovery of the radiopharmaceuticals was always higher than 97%. Two different methods of automation were developed for the formulation of [11C] and [18F]radiopharmaceuticals. In all cases, organic solvent levels in the injectable solution were below the recommended limits. This fast (3–6 min.) and easy to automate process can be considered as an alternative to the conventional methods (rotary evaporators). Copyright © 1999 John Wiley & Sons, Ltd.
Journal of Labelled Compounds 02/1999; 42(1):63 - 75.
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J P Royet,
O Koenig,
M C Gregoire,
L Cinotti,
F Lavenne, D Le Bars,
N Costes,
M Vigouroux,
V Farget,
G Sicard,
A Holley,
F Mauguière,
D Comar,
J C Froment
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ABSTRACT: The functional anatomy of perceptual and semantic processings for odors was studied using positron emission tomography (PET). The first experiment was a pretest in which 71 normal subjects were asked to rate 185 odorants in terms of intensity, familiarity, hedonicity, and comestibility and to name the odorants. This pretest was necessary to select the most appropriate stimuli for the different cognitive tasks of the second experiment. The second one was a PET experiment in which 15 normal subjects were scanned using the water bolus method to measure regional cerebral blood flow (rCBF) during the performance in three conditions. In the first (perceptual) condition, subjects were asked to judge whether an odor was familiar or not. In the second (semantic) condition, subjects had to decide whether an odor corresponded to a comestible item or not. In the third (detection) condition, subjects had to judge whether the perceived stimulus was made of an odor or was just air. It was hypothetized that the three tasks were hierarchically organized from a superficial detection level to a deep semantic level. Odorants were presented with an air-flow olfactometer, which allowed the stimulations to be synchronized with breathing. Subtraction of activation images obtained between familiarity and control judgments revealed that familiarity judgments were mainly associated with the activity of the right orbito-frontal area, the subcallosal gyrus, the left inferior frontal gyrus, the left superior frontal gyrus, and the anterior cingulate (Brodmann's areas 11, 25, 47, 9, and 32, respectively). The comestibility minus familiarity comparison showed that comestibility judgments selectively activated the primary visual areas. In contrast, a decrease in rCBF was observed in these same visual areas for familiarity judgments and in the orbito-frontal area for comestibility judgments. These results suggest that orbito-frontal and visual regions interact in odor processing in a complementary way, depending on the task requirements.
Journal of Cognitive Neuroscience 02/1999; 11(1):94-109. · 5.18 Impact Factor
