Cortical processing of noxious somatosensory stimuli in the persistent vegetative state.

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 [(18)F]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.

Effects of incidental and intentional feature binding on recognition: a behavioural and PET activation study.

Using Positron Emission Tomography (PET), we investigated cerebral regions associated with the episodic recognition of words alone and words bound to contextual colours. Two modes of colour encoding were tested: incidental and intentional word-to-colour binding. Word-only recognition was associated with brain activation in a lexico-semantic left middle temporal region and in the cerebellum following an incidental colour encoding, and with brain activation in the left posterior middle frontal gyrus, right anterior cingulate and right inferior frontal gyrus following an intentional encoding. Recognition of bound features was associated with activation in left prefrontal and superior parietal regions following an incidental colour encoding, and with preferential right prefrontal cortex activation following an intentional colour encoding. Our results are in line with the hypothesis of a parietal involvement in context processing, and prefrontal areas in monitoring retrieval processes. Our results also support the hypothesis of a 'cortical asymmetry for reflective activity' (CARA).

Experience-dependent changes in cerebral functional connectivity during human rapid eye movement sleep.

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.

Experience-dependent changes in cerebral activation during human REM sleep.

The function of rapid-eye-movement (REM) sleep is still 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.

Preoperative evaluation of 54 gliomas by PET with fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine.

UNLABELLED: This study evaluates the usefulness of PET for the preoperative evaluation of brain gliomas and methods of quantification of PET results. METHODS: Fifty-four patients with brain gliomas were studied by PET with 18F-fluorodeoxyglucose (FDG) (n = 45) and/or 11C-methionine (MET) (n = 41) before any treatment. Results of visual analysis, calculation of glucose consumption and five tumor-to-normal brain ratios for both tracers were correlated with two histologic grading systems and with follow-up. RESULTS: Visual analysis (for FDG) and tumor-to-mean cortical uptake (T/MCU) ratio proved to be the best tools for the evaluation of PET results. Methionine was proven to be better than FDG at delineating low-grade gliomas. Tumor-to-mean cortical uptake ratios for FDG and MET were clearly correlated (r = 0.78), leading to the equation T/MCU(FDG) = 0.4 x T/MCU(MET). We showed a good correlation between FDG PET and histologic grading. MET uptake could not differentiate between low-grade and anaplastic astrocytomas but was significantly increased in glioblastomas. Low-grade oligodendrogliomas exhibited high uptake of FDG and MET, probably depending more on oligodendroglial cellular differentiation than on proliferative potential. Uptake was decreased in anaplastic oligodendrogliomas, probably due to dedifferentiation. Care must be taken with peculiar histologic subgroups, i.e., juvenile pilocytic astrocytomas and oligodendrogliomas, because of a discrepancy between high PET metabolism and low proliferative potential (good prognosis). Both tracers proved useful for the prediction of survival prognosis. Methionine proved slightly superior to FDG for predicting the histologic grade and prognosis of gliomas, despite the impossibility of differentiation between Grades II and III astrocytomas with MET. This superiority of MET could be explained by patient sampling (low number of Grade III gliomas submitted to examination with both tracers). The combination of both tracers improved the overall results compared to each tracer alone. CONCLUSION: Both tracers are useful for the prediction of the histologic grade and prognosis. The apparent superiority of MET over FDG could be due to the small number of Grade III gliomas studied with both tracers.

Effect of exercise on the leg distribution of C15O2 and 15O2 in normals and in patients with peripheral ischemia: a study using positron tomography.

In order to evaluate regional muscle blood flow and oxygen utilization, we study with positron emission tomography (PET) the distribution of C15O2 and 15O2 in 17 subjects: 5 normals (24 +/- 3 years) and 12 patients (63 +/- 13.5 years). C15O2 and 15O2 are inhalated with a steady-state technique. Positron tomograms are recorded in supine position at the greatest diameter of the leg. Exercise consists in simultaneous ankle flexions. In all normals, C15O2 and 15O2 are distributed homogeneously and symmetrically in both legs. At rest, they concentrate in the region of vascular pedicle. After exercise, C15O2 and 15O2 are electively distributed in the anterolateral region of the leg. In patients, this pattern of distribution is similar but asymmetrical. Moreover, the regional uptake of C15O2 and 15O2 often dissociates. In conclusion, C15O2 and 15O2 allow to study repeatedly muscle blood flow and oxygen utilization in patients with peripheral ischemia, both at rest and after exercise. The broad spectrum of pathological changes observed in this study needs further metabolic investigations.

[Regional blood flow and oxygen consumption in the leg muscles of normal subjects and in those with arterial insufficiency. Study of the distribution of C15O2 and of 15O2 using positron emission tomography]. / Débit sanguin régional et extraction de l'oxygène dans les muscles de la jambe chez le sujet normal et l'insuffisant artériel. Etude de la distribution du C15O2 et de l'15O2 par tomographie à émission de positons.

We first studied the distribution of radioactivity during continuous inhalation of C15O2 and 15O2 in traverse tomograms of the greatest diameter of legs, at rest and immediately after exercise (ankle flexions). C15O2 and 15O2 were distributed homogeneously and symmetrically in both legs of normal subjects at rest. The activity accumulated in the anterolateral region after exercise. In patients, this pattern of distribution was similar but asymmetrical, depending on the arterial pathology. No systematic distribution of either C15O2 or 15O2 was observed. In a second step, we studied quantitatively blood flow (F), oxygen uptake (R) and oxygen extraction (E) in 11 subjects: 5 normals (23 +/- 1 years) and 6 patients (60 +/- 11 years) suffering from unilateral intermittent claudication. We used the bolus inhalation technique of C15O2 and 15O2. In the normal leg at rest, ranges were 2.5 to 8.0 ml/min.hg for F, 0.9 to 21.3 mumol/min.hg for R and 3.6 to 33.4% for E. In the pathological leg at rest, ranges were 3.7 to 11.3 ml/min.hg for F, 3.8 to 10.6 mumol/min.hg for R and 7.1 to 24.5% for E. After exercise, ranges were 6.4 to 62.8 ml/min.hg for F, 66.0 to 386.3 mumol/min.hg for R and 29.2 to 89.5% for E in both legs. There was no straight difference between normal and pathological legs soon after exercise. This study allows us to expect that the demonstration of such a difference implies a longer delay of data acquisition following the slow post-ischemia recovery.

Pulmonary regional ventilation. C15O2 single breath method. New technical improvements.

After a single inhalation of C15O2 labelled air, from residual volume to total lung capacity, followed by a few seconds apnea, it is possible to record in four or six lung zones the regional activity changes on a time basis. A first fast rise in activity is seen during the inhalation phase, corresponding to the ventilation in the region of interest (ROI). During the apnea, a slower decreasing component is observed in the different ROI, proportional to the regional blood flow, as almost instantaneously C15O2 is converted to labelled water. After the pioneer work of West & Dollery (1962) very few papers appeared on the subject despite technical improvements as, for instance, coincidence counting of radioactive events. We thus decided to improve the reproducibility and accuracy of the method which were of such a poor quality that no individual measurements were possible in the past. Were of critical importance: a careful positioning of the patients between the counters, a faster electronics improving true coincidence counting. In six healthy volunteers (age 22-35) the values obtained for regional ventilation with the C15O2 single breath were compared to the values given by the inhalation of a poorly soluble gas (Nitrogen13). The correlation between the two sets of measurements is high (r = 0.975). The slope of the regression line is 0.859, ordinate at origin is 2.35. This reveals a systematic error. A mathematical model was therefore developed to take into account the "washout" occurring during the constitution of the ventilation peak, and to correct its value.(ABSTRACT TRUNCATED AT 250 WORDS)

[Positron tomographic study of the behavior of 13N-labeled nitrous oxide in the human brain]. / Etude par tomographie à positron du comportement dans le cerveau humain protoxyde d'azote marqué à l'azote-13.

The synthesis of 13N-labelled nitrous oxide was made following NICKLES' method. After a partial denitrogenisation by breathing pure oxygen for 3 min, the subject inhaled a bolus of 13N-labelled nitrous oxide diluted in 2 l of oxygen (a mixture of 5% 13N2O and 95% O2). After an apnea of 30 sec the subject began to breathe in a closed respiratory system containing a mixture of 10% N2O and 90% O2. Eight images of the brain taken at level OM + 3 in 4 subjects showed an important uptake in the cerebellum and in the frontal and temporal cortex. Six min after inhalation of the bolus, the radioactivity in the cerebellum showed a clear decrease, whereas little decrease was observed in the frontal cortex and only a slight decrease in the temporal cortex. In order to suppress the activity due to the vascular comportment, an experiment was performed under the same conditions as the previous one, but using sodium pyrophosphate containing tin and 25 mCi of Tc-99m pertechnetate. The correction factors vary from 0.394 to 0.894 depending on the R.O.I. The activity curves after correction showed a predominance in the frontal cortex. It can therefore be concluded that some specific zones of the brain are receptive to N2O and in particular the frontal cortex. These results were compared with the data obtained from the electrophysiological recording of the frontal region of the brain (C.N.V.: Contingent Negative Variation).