Guy Delfiore

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. Language: en

Exploring the Unity and Diversity of the Neural Substrates of Executive Functioning

Previous studies exploring the neural substrates of executive functioning used task‐specific analyses, which might not be the most appropriate approach due to the difficulty of precisely isolating executive functions. Consequently, the aim of this study was to use positron emission tomography (PET) to reexamine by conjunction and interaction paradigms the cerebral areas associated with three executive processes (updating, shifting, and inhibition). Three conjunction analyses allowed us to isolate the cerebral areas common to tasks selected to tap into the same executive process. A global conjunction analysis demonstrated that foci of activation common to all tasks were observed in the right intraparietal sulcus, the left superior parietal gyrus, and at a lower statistical threshold, the left lateral prefrontal cortex. These regions thus seem to play a general role in executive functioning. The right intraparietal sulcus seems to play a role in selective attention to relevant stimuli and in suppression of irrelevant information. The left superior parietal region is involved in amodal switching/integration processes. One hypothesis regarding the functional role of the lateral prefrontal cortex is that monitoring and temporal organization of cognitive processes are necessary to carry out ongoing tasks. Finally, interaction analyses showed that specific prefrontal cerebral areas were associated with each executive process. The results of this neuroimaging study are in agreement with cognitive studies demonstrating that executive functioning is characterized by both unity and diversity of processes. Hum. Brain Mapp, 2005.

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. Hum. Brain Mapping 10:179–194, 2000.

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 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.

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 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 (Brodmanns area 10), spreading to the left middle frontal (Brodmanns area 46). Results suggest that frontopolar activation underlies an updating process in working memory.

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.

Modulation of Brain Activity during Phonological Familiarization.

We measured brain activity in 12 adults for the repetition of auditorily presented words and nonwords, before and after repeated exposure to their phonological form. The nonword phoneme combinations were either of high (HF) or low (LF) phonotactic frequency. After familiarization, we observed, for both word and nonword conditions, decreased activation in the left posterior superior temporal gyrus, in the bilateral temporal pole and middle temporal gyri. At the same time, interaction analysis showed that the magnitude of decrease of activity in bilateral posterior temporal lobe was significantly smaller for LF nonwords, relative to words and HF nonwords. Decrease of activity in this area also correlated with the size of behavioral familiarization effects for LF nonwords. The results show that the posterior superior temporal gyrus plays a fundamental role during phonological learning. Its relationship to sublexical and lexical phonological processing as well as to phonological short-term memory is discussed.

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 Alzheimers 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 measured 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.