Délégation Régionale Auvergne-Rhône-Alpes

Prehension movements were studied by film in 7 adult subjects. Transportation of the hand to the target-object location had features very similar to any aiming arm movement, that is, it involved a fast-velocity initial phase and a low-velocity final phase. The peak velocity of the movement was highly correlated with its amplitude, although total movement duration tended to remain invariant when target distance was changed. The low-velocity phase consistently began after about 75% of movement time had elapsed. This ration was maintained for different movement amplitudes. Formation of the finger grip occurred during hand transportation. Fingers were first stretched and then began to close in anticipation to contact with the object. The onset of the closure phase was highly correlated to the beginning of the low velocity phase of transportation. This pattern for both transportation and finger grip formation was maintained in conditions whether visual feedback from the moving limb was present or not. Implications of these findings for the central programming of multisegmental movements are discussed.

Global biodiversity in freshwater and the oceans is declining at high rates. Reliable tools for assessing and monitoring aquatic biodiversity, especially for rare and secretive species, are important for efficient and timely management. Recent advances in DNA sequencing have provided a new tool for species detection from DNA present in the environment. In this study, we tested whether an environmental DNA (eDNA) metabarcoding approach, using water samples, can be used for addressing significant questions in ecology and conservation. Two key aquatic vertebrate groups were targeted: amphibians and bony fish. The reliability of this method was cautiously validated in silico, in vitro and in situ. When compared with traditional surveys or historical data, eDNA metabarcoding showed a much better detection probability overall. For amphibians, the detection probability with eDNA metabarcoding was 0.97 (CI = 0.90-0.99) vs. 0.58 (CI = 0.50-0.63) for traditional surveys. For fish, in 89% of the studied sites, the number of taxa detected using the eDNA metabarcoding approach was higher or identical to the number detected using traditional methods. We argue that the proposed DNA-based approach has the potential to become the next-generation tool for ecological studies and standardized biodiversity monitoring in a wide range of aquatic ecosystems.

Visually directed arm movements have been studied by film recordings in 10 patients with optic ataxia resulting from unilateral lesions of the parietal region, in 3 cases on the right and in 7 on the left. Half of the patients also underwent visuospatial perceptive tests. The results indicate the following. (1) Optic ataxia is a specific visuomotor disorder, independent of visual space misperception. (2) The proximal and the distal components of the movements are equally affected as shown in reaching and hand orientation tasks. (3) The percentages of spatial and orientation errors quantified, respectively, in these two situations show a different distribution across the different hand-field combinations according to the side of the lesion: whereas the right-damaged patients show a deficit essentially related to a field effect, the left-damaged patients show in addition to the latter an impairment related to a hand effect. These findings suggest that the 2 types of visuomotor mechanisms responsible for the proximal and distal components of visually-directed arm movements are controlled by the parietal cortex and that there should exist a hemisphere asymmetry in the functional organization of these mechanisms. (4) Reconstruction of the lesions drawn from CT scans in 8 of the patients shows a salient and constant involvement of the posterior parietal cortex, always including the intraparietal sulcus and either the superior part of the inferior parietal lobule or more often various parts of the superior parietal lobule. The weak co-occurrence of optic ataxia and hemispatial neglect, and their different lesion sites, indicate a double dissociation between these two symptoms.

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.

This paper describes the OpenViBE software platform which enables researchers to design, test, and use brain–computer interfaces (BCIs). BCIs are communication systems that enable users to send commands to computers solely by means of brain activity. BCIs are gaining interest among the virtual reality (VR) community since they have appeared as promising interaction devices for virtual environments (VEs). The key features of the platform are (1) high modularity, (2) embedded tools for visualization and feedback based on VR and 3D displays, (3) BCI design made available to non-programmers thanks to visual programming, and (4) various tools offered to the different types of users. The platform features are illustrated in this paper with two entertaining VR applications based on a BCI. In the first one, users can move a virtual ball by imagining hand movements, while in the second one, they can control a virtual spaceship using real or imagined foot movements. Online experiments with these applications together with the evaluation of the platform computational performances showed its suitability for the design of VR applications controlled with a BCI. OpenViBE is a free software distributed under an open-source license.

The study of pain in awake animals raises ethical, philosophical, and technical problems. We review the ethical standards for studying pain in animals and emphasize that there are scientific as well as moral reasons for keeping to them. Philosophically, there is the problem that pain cannot be monitored directly in animals but can only be estimated by examining their responses to nociceptive stimuli; however, such responses do not necessarily mean that there is a concomitant sensation. The types of nociceptive stimuli (electrical, thermal, mechanical, or chemical) that have been used in different pain models are reviewed with the conclusion that none is ideal, although chemical stimuli probably most closely mimic acute clinical pain. The monitored reactions are almost always motor responses ranging from spinal reflexes to complex behaviors. Most have the weakness that they may be associated with, or modulated by, other physiological functions. The main tests are critically reviewed in terms of their sensitivity, specificity, and predictiveness. Weaknesses are highlighted, including 1) that in most tests responses are monitored around a nociceptive threshold, whereas clinical pain is almost always more severe; 2) differences in the fashion whereby responses are evoked from healthy and inflamed tissues; and 3) problems in assessing threshold responses to stimuli, which continue to increase in intensity. It is concluded that although the neural basis of the most used tests is poorly understood, their use will be more profitable if pain is considered within, rather than apart from, the body's homeostatic mechanisms.

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.

According to most behavioural, electrophysiological, and clinical studies, the cingulate gyrus is widely thought to be involved in regulation of emotional life, reactivity to painful stimuli, memory processing, and attention to sensory stimuli. Anatomically the cingulate cortex is composed of two distinct areas numbered 24 and 23 in Brodmann's classification. We have investigated the connections of the cingulate gyrus in monkeys, using horseradish peroxydase and radioautographic techniques, in order to verify the hypothesis of an anatomical complementarity of these cytoarchitectonic subdivisions. The posterior cingulate gyrus (area 23) is specifically connected with the associative temporal cortex, the medial temporal and orbitofrontal cortices, and with the medial pulvinar. The anterior cingulate gyrus (area 24) is related to the intralaminar, mediodorsal, and ventral anterior thalamic nuclei, the amygdala, and the nucleus accumbens septi. The two cingulate areas were found to be interconnected and to have, in common, connections with the 'limbic' thalamic nuclei (AM, AV, LD), the caudate nucleus, the claustrum, the lateral frontal and the posterior parietal (area 7) cortices.

Mouse embryonic stem cells were induced to differentiate in culture with retinoic acid. Putative precursors of neurons and glial cells (nestin-positive cells) were clearly identified as early as three days after the onset of differentiation. At day 6, neuron-like cells could be clearly identified, either as isolated cells or as cellular networks. Some of these cells were positive for astrocyte- or oligodendrocyte-specific antigens (GFAP or O4 antigens, respectively). Other cells were positive for neuron-specific antigens (cytoskeleton proteins MAP2, MAP5 and NF200, as well as synaptophysin). Some neuronal-like cells were also positive for acetylcholinesterase activity or glutamic acid decarboxylase expression, indicating that ES cells could differentiate into GABAergic and possibly cholinergic neurons. Electrophysiological analyses performed in voltage clamp conditions showed that cell membranes contained voltage-dependent channels. Overshooting action potentials could be triggered by current injection. Taken together, these data provide evidence that embryonic stem cells can differentiate first into neuron-glia progenitors, and later into glial cells and functional neurons, in vitro. This technique provides an unique system to study early steps of neuronal differentiation in vitro.

The role of lysophosphatidic acid (LPA) in cancer is poorly understood. Here we provide evidence for a role of LPA in the progression of breast cancer bone metastases. LPA receptors LPA(1), LPA(2), and LPA(3) were expressed in human primary breast tumors and a series of human breast cancer cell lines. The inducible overexpression of LPA(1) in MDA-BO2 breast cancer cells specifically sensitized these cells to the mitogenic action of LPA in vitro. In vivo, LPA(1) overexpression in MDA-BO2 cells enhanced the growth of subcutaneous tumor xenografts and promoted bone metastasis formation in mice by increasing both skeletal tumor growth and bone destruction. This suggested that endogenous LPA was produced in the tumor microenvironment. However, MDA-BO2 cells or transfectants did not produce LPA. Instead, they induced the release of LPA from activated platelets which, in turn, promoted tumor cell proliferation and the LPA(1)-dependent secretion of IL-6 and IL-8, 2 potent bone resorption stimulators. Moreover, platelet-derived LPA deprivation in mice, achieved by treatment with the platelet antagonist Integrilin, inhibited the progression of bone metastases caused by parental and LPA(1)-overexpressing MDA-BO2 cells and reduced the progression of osteolytic lesions in mice bearing CHO-beta3wt ovarian cancer cells. Overall, our data suggest that, at the bone metastatic site, tumor cells stimulate the production of LPA from activated platelets, which enhances both tumor growth and cytokine-mediated bone destruction.

The aim of the present study was to examine the timing of different responses given simultaneously to a single event, the sudden displacement of a visual object occurring at the onset of the grasping movement directed at that object. The subjects were requested to correct their movement in order to reach accurately for the object and to signal the time at which they became aware of its displacement by a simple vocal utterance (Tah!). The onset of the motor adjustment was measured using kinematic landmarks obtained from the hand trajectory. Movements executed during trials where the object was displaced had an earlier peak in acceleration (107 ms) than movements executed during control trials (120 ms). By contrast, the vocal signal occurred 420 ms following object displacement, that was more than 300 ms after the onset of the motor correction. Control experiments were performed in order to verify the influence of possible interferences between the two tasks. Motor corrections performed without vocal utterance had the same timing as when the vocal signal was produced. Vocal signals produced in response to object's displacements but in the absence of reaching movements had the same latency as when movements were performed. We conclude from these results that the two responses were generated independently of each other. Assuming that the vocal responses in this experiment did signal the subject's awareness, the observed delay between motor corrections and these responses suggests that neural activity must be processed during a significant and quantifiable amount of time before it can give rise to conscious experience. This dissociation between motor responses and awareness in normal subjects is discussed in the light of clinical cases where overt behaviour and conscious experience are dissociated by cerebral lesions.

The role of lysophosphatidic acid (LPA) in cancer is poorly understood. Here we provide evidence for a role of LPA in the progression of breast cancer bone metastases. LPA receptors LPA(1), LPA(2), and LPA(3) were expressed in human primary breast tumors and a series of human breast cancer cell lines. The inducible overexpression of LPA(1) in MDA-BO2 breast cancer cells specifically sensitized these cells to the mitogenic action of LPA in vitro. In vivo, LPA(1) overexpression in MDA-BO2 cells enhanced the growth of subcutaneous tumor xenografts and promoted bone metastasis formation in mice by increasing both skeletal tumor growth and bone destruction. This suggested that endogenous LPA was produced in the tumor microenvironment. However, MDA-BO2 cells or transfectants did not produce LPA. Instead, they induced the release of LPA from activated platelets which, in turn, promoted tumor cell proliferation and the LPA(1)-dependent secretion of IL-6 and IL-8, 2 potent bone resorption stimulators. Moreover, platelet-derived LPA deprivation in mice, achieved by treatment with the platelet antagonist Integrilin, inhibited the progression of bone metastases caused by parental and LPA(1)-overexpressing MDA-BO2 cells and reduced the progression of osteolytic lesions in mice bearing CHO-beta3wt ovarian cancer cells. Overall, our data suggest that, at the bone metastatic site, tumor cells stimulate the production of LPA from activated platelets, which enhances both tumor growth and cytokine-mediated bone destruction.

The retinal coordinates of an image are normally insufficient to define the direction of an object in body-centred visual space. Gaze direction, specified by information on the position of eye-in-head and on the position of head-on-torso, is also required. While the source of the eye-in-head signal is controversial, it is clear that proprioceptive signals from neck muscles are sufficient to provide head-on-torso information. Observations by Goodwin et al., beginning in 1972, that vibration of limb muscles modifies proprioception from them, and induces illusory motion and false perception of limb position, suggested this study of the effects of neck muscle vibration on the representation of visual space. Verbal reports, supported by objective measures, revealed that vibration of muscles on one side of the neck induces a visual illusion: contralateral displacement of a small visual target viewed in the dark. Pointing movements towards the target are similarly affected, confirming that the representation of directions in visual space is modified by neck muscle vibration. A second vibration-induced illusion was uncovered when apparent displacement ceased. This is an illusion of pure target motion in the same direction as the previously observed displacement. The magnitudes of both the displacement and pure motion illusions were dependent on vibration amplitude and were unrelated to real or apparent movements of eyes or head. Taken together these observations indicate that vibration of neck muscles can modify independently (1) the central representation of the instantaneous direction of gaze and (2) the signal of the velocity with which this direction is changing.

1. Healthy subjects actually performed and mentally simulated a leg exercise at two levels of work (15 and 19 kg loads). Heart rate, respiration rate and end-tidal PCO2 were measured in both conditions. In addition, muscular metabolism was simultaneously measured using 31P nuclear magnetic resonance (NMR) spectroscopy. 2. During actual exercise, heart and respiration rates increased, first abruptly and then gradually in relation to the level of work. End-tidal PCO2 was unaltered. NMR spectra showed a drop in phosphocreatine (PCr) and an increase in inorganic phosphate (Pi) concentrations. Intracellular pH fell to 6.65 at maximal effort with a 19 kg load. 3. During mental simulation, both heart and ventilatory rate increased immediately after mental exercise was begun. This increase was proportional to the amount of simulated exercise. Heart rate remained about 25% below the level observed during actual exercise. The increase in respiration rate, by contrast, was more marked than during actual exercise. Finally, end-tidal PCO2 decreased progressively to about 18% of the resting value. 4. During mental simulation, NMR spectra were unchanged with respect to the resting values. 5. Subjects rated their sensation of fatigue using an analog rating scale, during both actual exercise and mental simulation. During mental exercise, the sensation of fatigue was greater with the 19 kg load than with the 15 kg load. 6. These results demonstrate that mental simulation of action can activate heart and respiration control mechanisms. They suggest that autonomic activation during imagined action pertains to the more general phenomenon of preparation for action.

A number of lines of evidence suggest that, in the macaque monkey, inferior parietal and inferotemporal cortices process different types of visual information. It has been suggested that visual information reaching these two subdivisions follows separate pathways from the striate cortex through the prestriate cortex. We examined directly this possibility by placing injections of the retrograde fluorescent tracers, fast blue and diamidino yellow, in inferior parietal and inferotemporal cortex and examining the spatial pattern of cortical areas containing labeled cells in two-dimensional reconstructions of the cortex. The results of injections in inferotemporal cortex show that TEO receives afferents from areas V2, ventral V3, V3A, central V4, V4t, and DPL in prestriate cortex and from areas IPa, PGa, and FST in the superior temporal sulcus (STS). Area TEp receives afferents only from V4 in prestriate cortex and from IPa, PGa, and FST in the anterior STS. Area TEa receives no prestriate input and is innervated by IPa, PGa, FST, and TPO in the anterior STS. The results of injections in inferior parietal cortex demonstrate that POa receives afferents from dorsal V3, V3A, peripheral V4, DPL, and PO in prestriate cortex, from MST and *VIP and from IPa, PGa, TPO, and FST in anterior STS. Area PGc (corresponding to 7a) is innervated by PO, MST, and by TPO in the anterior STS. Examination of the two-dimensional reconstructions of the pattern of labeling after combined injections of fast blue and diamidino yellow in areas POa and TEO revealed that these areas are principally innervated by different prestriate areas. Only a small region, centered on area V3A and extending into V4 and DPL, contained cells labeled by either injection as well as a small number of double-labeled cells. In contrast, areas POa and TEO receive afferents from extensive common regions in the anterior STS corresponding to areas IPa, PGa, and FST. These results directly demonstrate that visual information from the striate cortex reaches inferior parietal and inferotemporal cortices through largely separate prestriate cortical pathways. On the other hand, both parietal and inferotemporal cortices receive common inputs from extensive regions in the anterior STS which map play a role in linking the processing occurring in these two cortical subdivisions of the visual system.

Connections of the posterior parietal cortex (area 7) with subcortical structures related to the vestibulo-ocular function were studied on four macaque monkeys by using anterograde and retrograde tracer. Wheat germ agglutinin (WGA)-horseradish peroxidase (HRP) or tritiated amino acids were injected into the posterior part of area 7, including the caudal end of the superior bank of both the superior temporal sulcus and the lateral sulcus. The posterior parietal cortex was found to be reciprocally connected with three different ipsilateral thalamic nuclei: the nucleus ventralis posterior inferior, the magnocellular part of the medial geniculate nucleus, and some intralaminar nuclei. Through these connections, area 7 might control the vestibulo-ocular response (VOR) by modulating the ascending vestibular information. This cortical area 7 also projects to the ipsilateral intermediate and deep layers of the superior colliculus and to several ipsilateral pontine nuclei. The dorsolateral pontine nucleus is of particular interest because it is known to be related to smooth pursuit eye movements. Cortical area 7 also was seen to project to the accessory nucleus of Darkschewitsch, to all the vestibular nuclei, and to the nucleus propositus hypoglossi; the last two projections were found to be bilateral with a greater ipsilateral contribution. Efferents from posterior parietal cortex are directed to precise regions within the vestibular nuclei that are specifically involved in vestibulo-ocular reflex, or that are in turn connected with brainstem structures implicated in smooth pursuit eye movements. These connections are consistent with the posterior parietal cortex exerting a multilevel influence on the different systems dealing with eye-head movement coordination.

Dendritic morphology has a profound impact on neuronal information processing. The overall extent and orientation of dendrites determines the kinds of input a neuron receives. Fine dendritic appendages called spines act as subcellular compartments devoted to processing synaptic information, and the dendritic branching pattern determines the efficacy with which synaptic information is transmitted to the soma. The acquisition of a mature dendritic morphology depends on the coordinated action of a number of different extracellular factors. Here we discuss this evidence in the context of dendritic development in the cerebral cortex. Soon after migrating to the cortical plate, neurons extend an apical dendrite directed toward the pial surface. The oriented growth of the apical dendrite is regulated by Sema3A, which acts as a dendritic chemoattractant. Subsequent dendritic development involves signaling by neurotrophic factors and Notch, which regulate dendritic growth and branching. During postnatal development the formation and stabilization of dendritic spines are regulated in part by patterns of synaptic activity. These observations suggest that extracellular signals play an important role in regulating every aspect of dendritic development and thereby exert a critical influence on cortical connectivity.

Working memory involves the short-term storage and manipulation of information necessary for cognitive performance, including comprehension, learning, reasoning and planning. Although electroencephalogram (EEG) rhythms are modulated during working memory, the temporal relationship of EEG oscillations with the eliciting event has not been well studied. In particular, the dynamics of the neural network supporting memory processes may be best captured in induced oscillations, characterized by a loose temporal link with the stimulus. In order to differentiate induced from evoked functional processes, the present study proposes a time-frequency analysis of the 3 to 30 Hz EEG oscillatory activity in a verbal n-back working memory paradigm. Control tasks were designed to identify oscillatory activity related to stimulus presentation (passive task) and focused attention to the stimulus (detection task). Evoked theta activity (4-8 Hz) phase-locked to the visual stimulus was evidenced in the parieto-occipital region for all tasks. In parallel, induced theta activity was recorded in the frontal region for detection and n-back memory tasks, but not for the passive task, suggesting its dependency on focused attention to the stimulus. Sustained induced oscillatory activity was identified in relation to working memory in the theta and beta (15-25 Hz) frequency bands, larger for the highest memory load. Its late occurrence limited to nonmatched items suggests that it could be related to item retention and active maintenance for further task requirements. Induced theta and beta activities displayed respectively a frontal and parietal topographical distribution, providing further functional information on the fronto-posterior network supporting working memory.

The human brain is expert in analyzing rapidly and precisely facial features, especially emotional expressions representing a powerful communication vector. The involvement of insula in disgust recognition has been reported in behavioral and functional imaging studies. However, we do not know whether specific insular fields are involved in disgust processing nor what the processing time course is. Using depth electrodes implanted during presurgical evaluation of patients with drug-refractory temporal lobe epilepsy, we recorded intracerebral event-related potentials to human facial emotional expressions, that is, fear, disgust, happiness, surprise, and neutral expression. We studied evoked responses in 13 patients with insular contacts to specify the insular fields involved in disgust processing and assess the timing of their activation. We showed that specific potentials to disgust beginning 300 milliseconds after stimulus onset and lasting 200 milliseconds were evoked in the ventral anterior insula in four patients. The occurrence and latency of event-related potentials to disgust in the ventral anterior insula were affected by selective attention. The analysis of spatial and temporal characteristics of insular responses to disgust facial expression lead us to underline the crucial role of ventral anterior insula in the categorization of facial emotional expressions, particularly the disgust.

In the last few years, the study of environmental DNA (eDNA) has drawn attention for many reasons, including its advantages for monitoring and conservation purposes. So far, in aquatic environments, most of eDNA research has focused on the detection of single species using species-specific markers. Recently, species inventories based on the analysis of a single generalist marker targeting a larger taxonomic group (eDNA metabarcoding) have proven useful for bony fish and amphibian biodiversity surveys. This approach involves in situ filtering of large volumes of water followed by amplification and sequencing of a short discriminative fragment from the 12S rDNA mitochondrial gene. In this study, we went one step further by investigating the spatial representativeness (i.e. ecological reliability and signal variability in space) of eDNA metabarcoding for large-scale fish biodiversity assessment in a freshwater system including lentic and lotic environments. We tested the ability of this approach to characterize large-scale organization of fish communities along a longitudinal gradient, from a lake to the outflowing river. First, our results confirm that eDNA metabarcoding is more efficient than a single traditional sampling campaign to detect species presence, especially in rivers. Second, the species list obtained using this approach is comparable to the one obtained when cumulating all traditional sampling sessions since 1995 and 1988 for the lake and the river, respectively. In conclusion, eDNA metabarcoding gives a faithful description of local fish biodiversity in the study system, more specifically within a range of a few kilometers along the river in our study conditions, i.e. longer than a traditional fish sampling site.