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Biomedical subjects

N Costes

Publications and source records attributed to N Costes.

6 recordsLinked to original sources

Chiral dihydroxylation of acronycine: absolute configuration of natural cis-1,2-dihydroxy-1,2-dihydroacronycine and cytotoxicity of (1R,2R)- and (1S,2S)-1,2-diacetoxy-1,2-dihydroacronycine.

Sharpless asymmetric dihydroxylation of acronycine (1) gave (1R, 2R)-1,2-dihydroxy-1,2-dihydroacronycine (2) and (1S,2S)-1, 2-dihydroxy-1,2-dihydroacronycine (3), which allowed determination of the absolute configuration of natural cis-1,2-dihydroxy-1, 2-dihydroacronycine as 1R,2R. The cis isomer had been previously isolated from various Sarcomelicope species. Benzylic reduction of isomers 2 and 3 gave the alcohols 4 (2R) and 5 (2S), respectively. Acetylation of 2 and 3 afforded the corresponding esters 6 and 7. No significant difference of cytotoxicity was observed between these (1R,2R)- and (1S,2S)-enantiomers and the recently described, highly active racemic cis-1,2-diacetoxy-1,2-dihydroacronycine, when tested against L-1210 cells in vitro.

Acronine

The effects of learning and intention on the neural network involved in the perception of meaningless actions.

PET was used to explore the neural network involved in the perception of meaningless action. In two conditions, subjects observed learned and unknown meaningless actions without any purpose. In two other conditions, subjects observed the same type of stimuli for later imitation. The control condition, which consisted of the presention of stationary hands, served as a baseline. Unsurprisingly, a common network that forms part of the dorsal pathway was engaged in all conditions when compared with stationary hands, and this was interpreted as being devoted to the analysis of hand movements. One of the most striking results of the present study was that some brain areas were strongly modulated by the learning level, independent of the subject's intention. Two different effects were observed: a reduced activity in posterior regions within the common network, which correlated with specific increases in the frontopolar area 10 and in the angular gyrus during the perception of learned meaningless actions compared with the perception of unknown actions. Finally, the major effect of the subject's intention to imitate was a strong increase in the dorsal pathway extending to the lateral premotor cortex and to the dorsolateral prefrontal cortex, which reflects the information processing needed for prospective action. Overall, our results provide evidence for both an effect of the visuomotor learning level and of the subject's intention on the neural network involved during the perception of human meaningless actions.

Adult

Haemodynamic brain responses to acute pain in humans: sensory and attentional networks.

Turning attention towards or away from a painful heat stimulus is known to modify both the subjective intensity of pain and the cortical evoked potentials to noxious stimuli. Using PET, we investigated in 12 volunteers whether pain-related regional cerebral blood flow (rCBF) changes were also modulated by attention. High (mean 46.6 degrees C) or low (mean 39 degrees C) intensity thermal stimuli were applied to the hand under three attentional conditions: (i) attention directed towards the stimuli, (ii) attention diverted from the stimuli, and (iii) no task. Only the insular/second somatosensory cortices were found to respond whatever the attentional context and might, therefore, subserve the sensory-discriminative dimension of pain (intensity coding). In parallel, other rCBF changes previously described as 'pain-related' appeared to depend essentially on the attentional context. Attention to the thermal stimulus involved a large network which was primarily right-sided, including prefrontal, posterior parietal, anterior cingulate cortices and thalamus. Anterior cingulate activity was not found to pertain to the intensity coding network but rather to the attentional neural activity triggered by pain. The attentional network disclosed in this study could be further subdivided into a non-specific arousal component, involving thalamic and upper brainstem regions, and a selective attention and orientating component including prefrontal, posterior parietal and cingulate cortices. A further effect observed in response to high intensity stimuli was a rCBF decrease within the somatosensory cortex ipsilateral to stimulation, which was considered to reflect contrast enhancing and/or anticipation processes. Attentional processes could possibly explain part of the variability observed in previous PET reports and should therefore be considered in further studies on pain in both normal subjects and patients with chronic pain.

Acoustic Stimulation

Functional anatomy of perceptual and semantic processing for odors.

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.

Adult

Visual working memory for shape and 3D-orientation: a PET study.

In order to determine the neural substrate of working memory for shape and 3D-orientation, regional cerebral blood flow (rCBF) changes were estimated using positron emission tomography (PET). Subjects were scanned during the performance of two delayed-matching-to-sample tasks using flat polydedrical objects of different shapes and 3D-orientations presented in a virtual environment. The shape matching task was associated with activation in the occipito-temporal junction, occipito-parietal cortex and mesial frontal pole of the right hemisphere. During the orientation matching task, rCBF increased in the mesial occipito-temporal cortex, superior temporal gyrus and middle frontal gyrus of the left hemisphere. The right supramarginal gyrus was also activated. These results suggest that both visual pathways are engaged in the processing of objects presented in different orientations. The dorsal stream is involved mainly in working memory of 3D-orientation, while the ventral stream is involved especially in shape working memory.

Adult

Brain activity during observation of actions. Influence of action content and subject's strategy.

PET was used to map brain regions that are associated with the observation of meaningful and meaningless hand actions. Subjects were scanned under four conditions which consisted of visually presented actions. In each of the four experimental conditions, they were instructed to watch the actions with one of two aims: to be able to recognize or to imitate them later. We found that differences in the meaning of the action, irrespective of the strategy used during observation, lead to different patterns of brain activity and clear left/right asymmetries. Meaningful actions strongly engaged the left hemisphere in frontal and temporal regions while meaningless actions involved mainly the right occipitoparietal pathway. Observing with the intent to recognize activated memory-encoding structures. In contrast, observation with the intent to imitate was associated with activation in the regions involved in the planning and in the generation of actions. Thus, the pattern of brain activation during observation of actions is dependent both on the nature of the required executive processing and the type of the extrinsic properties of the action presented.

Adult