A PET investigation of lexicality and phonotactic frequency in oral language processing.

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.

Contribution of lexico-semantic processes to verbal short-term memory tasks: a PET activation study.

Recent studies have demonstrated the intervention of long-term memory processes in verbal STM tasks and several cognitive models have been proposed to explain these effects. A PET study was performed in order to determine whether supplementary cerebral areas are involved when subjects have to execute short-term memory tasks for items having representations in long-term memory (in comparison to items without such representations: words vs non-words). Results indicate that verbal STM for words specifically involves the left middle temporal gyrus (BA 21) and temporo-parietal junction (BA 39). These areas can be associated with lexical and semantic processes. These results are in agreement with cognitive models that postulate the simultaneous influence of lexical and semantic long-term representations on verbal STM processes and/or a lexico-semantic buffer.

Generation of rapid eye movements during paradoxical sleep in humans.

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.

The functional anatomy of inhibition processes investigated with the Hayling task.

The cortical areas involved in inhibition processes were examined with positron emission tomography (PET). The tasks administered to subjects were an adaptation of the Hayling test. In the first condition (response initiation), subjects had to complete sentences with a word clearly suggested by the context, whereas in the second condition (response inhibition), subjects had to produce a word that made no sense in the context of the sentence. Results indicated that the response initiation processes were associated to increases of activity in the left inferior frontal gyrus (BA 45/47), whereas response inhibition processes led to increases in a network of left prefrontal areas, including the middle (BA 9 and BA 10) and inferior (BA 45) frontal areas.

Striatum forever, despite sequence learning variability: a random effect analysis of PET data.

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.

The role of lateral occipitotemporal junction and area MT/V5 in the visual analysis of upper-limb postures.

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.

Neural mechanisms of antinociceptive effects of hypnosis.

BACKGROUND: The neural mechanisms underlying the modulation of pain perception by hypnosis remain obscure. In this study, we used positron emission tomography in 11 healthy volunteers to identify the brain areas in which hypnosis modulates cerebral responses to a noxious stimulus. METHODS: The protocol used a factorial design with two factors: state (hypnotic state, resting state, mental imagery) and stimulation (warm non-noxious vs. hot noxious stimuli applied to right thenar eminence). Two cerebral blood flow scans were obtained with the 15O-water technique during each condition. After each scan, the subject was asked to rate pain sensation and unpleasantness. Statistical parametric mapping was used to determine the main effects of noxious stimulation and hypnotic state as well as state-by-stimulation interactions (i.e., brain areas that would be more or less activated in hypnosis than in control conditions, under noxious stimulation). RESULTS: Hypnosis decreased both pain sensation and the unpleasantness of noxious stimuli. Noxious stimulation caused an increase in regional cerebral blood flow in the thalamic nuclei and anterior cingulate and insular cortices. The hypnotic state induced a significant activation of a right-sided extrastriate area and the anterior cingulate cortex. The interaction analysis showed that the activity in the anterior (mid-)cingulate cortex was related to pain perception and unpleasantness differently in the hypnotic state than in control situations. CONCLUSIONS: Both intensity and unpleasantness of the noxious stimuli are reduced during the hypnotic state. In addition, hypnotic modulation of pain is mediated by the anterior cingulate cortex.

Functional neuroanatomy of hypnotic state.

BACKGROUND: The aim of the present study was to describe the distribution of regional cerebral blood flow during the hypnotic state (HS) in humans, using positron-emission tomography (PET) and statistical parametric mapping. METHODS: The hypnotic state relied on revivification of pleasant autobiographical memories and was compared to imaging autobiographical material in "normal alertness." A group of 9 subjects under polygraphic monitoring received six H215O infusions and was scanned in the following order: alert-HS-HS-HS with color hallucination-HS with color hallucination-alert. PET data were analyzed using statistical parametric mapping (SPM95). RESULTS: The group analysis showed that hypnotic state is related to the activation of a widespread, mainly left-sided, set of cortical areas involving occipital, parietal, precentral, premotor, and ventrolateral prefrontal cortices and a few right-sided regions: occipital and anterior cingulate cortices. CONCLUSIONS: The pattern of activation during hypnotic state differs from those induced in normal subjects by the simple evocation of autobiographical memories. It shares many similarities with mental imagery, from which it differs by the relative deactivation of precuneus.

Regional brain activity during tasks devoted to the central executive of working memory.

Most previous PET studies investigating the central executive (CE) component of working memory found activation in the prefrontal cortex. However, the tasks used did not always permit to distinguish precisely the functions of the CE from the storage function of the slave systems. The aim of the present study was to isolate brain areas that subserve manipulation of information by the CE when the influence of storage function was removed. A PET activation study was performed with four cognitive tasks, crossing conditions of temporary storage and manipulation of information. The manipulation of information induced an activation in the right (BA 10/46) and left (BA 9/6) middle frontal gyrus and in the left parietal area (BA7). The interaction between the storage and manipulation conditions did not reveal any significant changes in activation. These results are in agreement with the hypothesis that CE functions are distributed between anterior and posterior brain areas, but could also reflect a simultaneous involvement of controlled (frontal) and automatic (parietal) attentional systems. In the other hand, the absence of interaction between the storage and manipulation conditions demonstrates that the CE is not necessarily related to the presence of a memory load.

The neural correlates of updating information in verbal working memory.

The aim of the present study was to re-examine cerebral areas subserving the updating function of the central executive with a running span task requiring subjects to watch strings of consonants of unknown length and then to recall serially a specific number of recent items. In order to dissociate more precisely the updating process from the storage function, a four-item instead of a six-item memory load was used, contrary to our previous study (Salmon et al., 1996). In addition, a serial recall procedure was preferred to a recognition procedure in order to suppress the use of visuospatial strategies. The most significant increase of rCBF occurred in the left frontopolar cortex (Brodmann's area 10), spreading to the left middle frontal (Brodmann's area 46). Results suggest that frontopolar activation underlies an updating process in working memory.

Functional neuroanatomy of human slow wave sleep.

The distribution of regional cerebral blood flow (rCBF) was estimated during sleep and wakefulness by using H215O positron emission tomography (PET) and statistical parametric mapping. A group analysis on 11 good sleepers (8 with steady slow wave sleep, SWS) showed a significant negative correlation between the occurrence of SWS and rCBF in dorsal pons and mesencephalon, thalami, basal ganglia, basal forebrain/hypothalamus, orbitofrontal cortex, anterior cingulate cortex, precuneus, and, on the right side, in a region that follows the medial aspect of the temporal lobe. Given the known decrease in global cerebral blood flow levels during SWS, these negative correlations suggest that rCBF is decreased significantly more in these cerebral areas than in the rest of the brain. The marked rCBF decreases in the pons, mesencephalon, thalamic nuclei, and basal forebrain reflect their close implication in the generation of SWS rhythms. The influence of these rhythms on the telencephalon usually are thought to be global and homogeneous. In contrast, our results show that rCBF is decreased more in some cortical areas (especially in orbitofrontal cortex) than in the rest of the cortex. We hypothesize that cellular processes taking place during SWS might be modulated differently in these regions. Given the functions of the ventromedial frontal areas, we surmise that SWS might be particularly critical for the adaptation of behavior to environmental pressures. This hypothesis is supported indirectly by results of sleep deprivation experiments.

Regional brain activity during working memory tasks.

The first aim of our PET study was to replicate previous findings concerning the brain areas activated by a verbal working memory task. The second aim was to specify the neural basis of the central executive, using a task of working memory updating. Our data confirm that the lower left supramarginal gyrus and premotor area are the key regions subserving short-term verbal memory processes. They also suggest that the updating memory task is related to middorsolateral prefrontal activation, most probably responsible for the updating function of the central executive. An unexpected, predominantly right activation occurred in the inferior parietal region during the verbal memory updating task, which we related to a visuospatial strategy used to maintain the information in short-term memory. A third purpose was to explore the brain regions activated by a nonverbal, visual memory task, and our results confirm the importance of the superior occipital gyrus in the visual short-term memory.

Functional neuroanatomy of human rapid-eye-movement sleep and dreaming.

Rapid-eye-movement (REM) sleep is associated with intense neuronal activity, ocular saccades, muscular atonia and dreaming. The function of REM sleep remains elusive and its neural correlates have not been characterized precisely in man. Here we use positron emission tomography and statistical parametric mapping to study the brain state associated with REM sleep in humans. We report a group study of seven subjects who maintained steady REM sleep during brain scanning and recalled dreams upon awakening. The results show that regional cerebral blood flow is positively correlated with REM sleep in pontine tegmentum, left thalamus, both amygdaloid complexes, anterior cingulate cortex and right parietal operculum. Negative correlations between regional cerebral blood flow and REM sleep are observed bilaterally, in a vast area of dorsolateral prefrontal cortex, in parietal cortex (supramarginal gyrus) as well as in posterior cingulate cortex and precuneus. Given the role of the amygdaloid complexes in the acquisition of emotionally influenced memories, the pattern of activation in the amygdala and the cortical areas provides a biological basis for the processing of some types of memory during REM sleep.

Combined study of cerebral glucose metabolism and [11C]methionine accumulation in probable Alzheimer's disease using positron emission tomography.

There is a characteristic decrease in glucose metabolism in associative frontal and temporo-parietal cortices of patients suffering from Alzheimer's disease (AD). The decrease in metabolism might result from local neuronal loss or from a decrease of synaptic activity. We measured in vivo [11C]methionine accumulation into proteins with positron emission tomography (PET) to assess cortical tissue loss in AD. Both global regional activity and compartmental analysis were used to express [11C]methionine accumulation into brain tissue. Glucose metabolism was measures with [18F]fluorodeoxyglucose and autoradiographic method. Combined studies were performed in 10 patients with probable AD, compared to age-matched healthy volunteers. There was a significant 45% decrease of temporo-parietal glucose metabolism in patients with AD, and frontal metabolism was lowered in most patients. Temporo-parietal metabolism correlated to dementia severity. [11C]methionine incorporation into temporo-parietal and frontal cortices was not significantly decreased in AD. There was no correlation with clinical symptoms. Data suggest that regional tissue loss, assessed by the decrease of [11C]methionine accumulation, is not sufficient to explain cortical glucose hypometabolism, which reflects, rather, reduced synaptic connectivity.

Brain activation induced by estimation of duration: a PET study.

Duration information about a visual stimulus requires processing as do other visual features such as size or intensity. Using positron emission tomography, iterative H215O infusions, and statistical parametric mapping, we investigated the neural correlates of time processing. Nine normal subjects underwent six serial rCBF. Three tasks were studied: (a) A temporal generalization task (D task) in which the subjects had to judge (by pressing one of two keys) whether the duration of the illumination of a green LED was equal to or different from that of a previously presented standard; (b) An intensity generalization task (I task) in which the judgment concerned the intensity of the LED; and (c) A control task (C task) in which the subjects had to press one of the two keys at random in response to LED illumination. A significant increase in rCBF during the D task, compared to that during the C task, was observed in right prefontal cortex, right inferior parietal lobule, anterior cingulate cortex, vermis, and a region corresponding to the left fusiform gyrus. A significant increase in rCBF during the I task, compared to that during the C task, was observed in right prefontal cortex, right inferior parietal lobule, right extrastriate cortex, anterior cingulate cortex, left inferior parietal lobule, vermis, and two symmetrical regions corresponding to the fusiform gyri. No significant activation was observed in the D task when compared to that in the I task. We propose that these cortical maps are best explained by the recruitment of visual attention and memory structures, which play a major role in prospective time judgements as indicated by behavioral studies. The data also suggest that the temporal dimension of a visual stimulus is processed in the same areas as other visual attributes.

[Study of cerebral metabolism and blood flow in partial complex epilepsy and status epilepticus in man using positron emission tomography]. / Etude chez l'homme, par tomographie à émission de positons, du métabolisme et du débit sanguin cérébral dans les épilepsies partielles complexes et dans différents états de mal.

Positron Emission Tomography (PET) with the oxygen-15 steady state inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen consumption (CMRO2) and oxygen extraction ratio (OER) in 25 patients with partial complex seizures during the interictal state, in 1 patient with recurrent temporal seizures and in 3 patients whose EEGs were characterized by periodic lateralized epileptiform discharges (PLEDs). Interictal scans showed temporal zone(s) of hypoperfusion and hypometabolism in 80% of patients with normal X-ray CT Scan. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the EEG abnormalities. Comparison of the different values of CBF, CMRO2 and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease in OER, the latter was always the most prominent in the region of the focus determined by serial EEG recordings. The observed imbalance between blood flow and oxidative glucose metabolism could suggest an impairment of O2 utilization by the mitochondria in the epilepticus focus during seizures or status epilepticus.

Myocardial blood flow and glucose uptake after myocardial infarction.

Position emission tomography can picture the distribution of flow tracers as well as of metabolic substrates or analogs. Studies of the distribution of these tracers allow to infer information about regional myocardial clearance (flow X extraction) and substrate utilization. In a study of 32 patients after myocardial infarction, we have contrasted flow and substrate utilization to demonstrate ischemic but viable myocardium in the arterial territory of the infarct in a number of patients also specially after fibrinolytic reperfusion. Restoration of blood flow to the ischemic but viable myocardium through coronary bypass or dilatation improves flow from 56.3% to 84.2% of control and restores substrate utilization. In another group of 32 patients studied with the Strontium-82/Rubidium-82 generator, we have demonstrated perfusion changes both in the myocardial infarct area and at a distance. These changes predominate in patients with multiple vessel disease. Combined PET studies of flow and substrate utilization are new tools to study early intervention after myocardial infarction and to document the benefits of revascularization.

Regional cerebral blood flow and metabolic rates in human focal epilepsy and status epilepticus.

Positron emission tomography with the oxygen-15 steady state or bolus inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen extraction ratio (OER) and oxygen consumption (CMRO2) in 25 patients with partial complex seizures during the interictal state and in 5 patients during status epilepticus. Glucose utilization (CMRglu) was also studied in one case of status epilepticus with the 18F-fluorodeoxyglucose technique (18FDG). Interictal scans showed zone(s) of hypoperfusion and hypometabolism without significant variation of the OER in approximately 80% of patients. In 62%, there was a strong correlation between the overall EEG localization and the area(s) of hypoperfusion and hypometabolism. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the electroencephalograph (EEG) abnormalities. Comparison of the different values of CBF, CMRO2, and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease of OER; the latter was always the most prominent in the region of the epilepticus focus determined by serial EEG recordings. These results showed that the supply of oxygen by blood flow is large enough to meet metabolic demand. When comparing these values with CMRglu, it appeared that the relative changes in CMRglu and CBF were very similar, indicating that the increase in blood flow correlated with the enhancement in glucose utilization. The observed imbalance between blood flow, glucose utilization, and oxygen consumption could suggest that an impairment of oxygen utilization by the mitochondria could occur in the epileptic focus during prolonged status epilepticus.

Radiocardiographic evaluation of left ventricular function after inhalation of C15O2.

Inhalation of C15O2 delivers a bolus of labelled water into the pulmonary veins and the left atrium; analysis of the left ventricular curve provides an easy method for the evaluation of left ventricular function. the patient was seated before six collimated probes positioned toward the lungs. An additional probe was directed toward the heart in a modified 15 to 20 degrees left anterior oblique projection. One to two mCi C15O2 was administered per study. The left ventricular curve was analysed and the ejection fraction was calculated using a new method. The background was first calculated for the cycle with the largest diastolic counts using characteristic points of the curve before and after transit of the indicator through the left ventricle. For the other cycles, the background was considered to be a constant fraction of the end-diastolic counts. The left ventricular ejection fraction was obtained for each cycle after corresponding background subtraction as the ratio of diastolic activity minus systolic activity over diastolic activity. The ejection fraction thus determined in 20 patients was highly reproducible from beat to beat and from study to study in the same patient (r = 0.97 and 0.96). It corresponded closely to the ejection fraction determined using a camera-computer system (r = 0.92). We conclude that C15O2 inhalation is an easy, rapid, reproducible and attractive method to assess left ventricular function.