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Mottet B.,Joseph Fourier University | Mottet B.,University Hospital | Chiquet C.,Joseph Fourier University | Chiquet C.,University Hospital | And 6 more authors.
Investigative Ophthalmology and Visual Science | Year: 2012

Purpose. We evaluated the supine 24-hour IOP rhythm reproducibility over 6 weeks in healthy humans. Methods. Six healthy young male subjects underwent six 24-hour sessions of IOP measurements over a 6-week period. Subjects were housed in a sleep laboratory in a constant controlled supine position and in a strictly controlled environment. IOP was measured hourly using a pneumatonometer. A nonlinear least-squares dual harmonic regression analysis was used to model the 24-hour IOP rhythm. The intra- and intersubject variability of acrophase, bathyphase, amplitude, and IOP values were evaluated. Results. A significant nyctohemeral IOP rhythm was noted in 30 of 36 (83%) sessions. Mean nocturnal IOP was significantly higher than diurnal IOP (20.1 ± 0.2 mm Hg [SD] vs. 18.8 ± 0.1 mm Hg, P < 0.001) in all subjects. Amplitudes were not statistically different among subjects (P = 0.52). In contrast, acrophase and bathyphase were statistically different (P < 0.05). Intrasubject homogeneity of distribution over time of the acrophase and bathyphase was significant in 3 of 6 and 4 of 6 subjects, respectively. Intraclass correlation coefficients of midline estimating statistic of rhythm (MESOR) and IOP values at 2:00, 3:00, 4:00, 10:00, and 11:00 AM, and 2:00 PM showed fair to good agreement among sessions. Conclusions. In a constant supine position, all subjects exhibited a nyctohemeral IOP rhythm present at an average rate of 80% of all sessions. With the currently available methods of tonometry, intrasubject reproducibility of rhythmic parameters and IOP values is limited. IOP values in the morning and IOP MESOR were the most reproducible parameters among the six visits. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Gerardin P.,Stem Cell and Brain Research Institute | Gerardin P.,University of Lyon | Nicolas J.,University of Lyon | Farne A.,University of Lyon | Pelisson D.,University of Lyon
Investigative Ophthalmology and Visual Science | Year: 2015

PURPOSE. Visual exploration relies on saccadic eye movements and attention processes. Saccadic adaptation mechanisms, which calibrate the oculo motor commands to continuously maintain the accuracy of saccades, have been suggested to act at downstream (motor) andupstream (visuoattentional) levels of visuo motor transformation. Conversely, whether attention can directly affect saccadic adaptation remains unknown. To answer this question, we manipulated the level of attention engaged in a visual discrimination task performed during saccadic adaptation. METHODS. Participants performed low or high attention demanding orientation discrimination tasks on largely or faintly oriented Gabor patches, respectively, which served as targets for reactive saccades. Gabor patches systematically jumped backward during eye motion to elicit an adaptive shortening of saccades, and replaced 50 msec later (100 msec in two subjects) by a mask. Subjects judged whether Gabors’ orientation was “nearly horizontal” versus “nearly vertical” (low attention demanding) or “slightly left” versus “slightly right” (high attention demanding), or made no discrimination (control task). RESULTS. We found that the build-up and the retention of adaptation of reactive saccades were larger in the “high attention demanding” condition than in the “low attention demanding” and the no-discrimination control conditions. CONCLUSIONS. These results indicate that increasing the level of attention to the perceptual processing of otherwise identical targets boosts saccadic adaptation, and suggest that saccadic adaptation mechanisms and attentional load effects may functionally share common neural substrates. © 2015 The Association for Research in Vision and Ophthalmology, Inc.

Lallee S.,Stem Cell and Brain Research Institute | Pattacini U.,Italian Institute of Technology | Lemaignan S.,CNRS Laboratory for Analysis and Architecture of Systems | Lenz A.,Bristol Robotics Laboratory | And 13 more authors.
IEEE Transactions on Autonomous Mental Development | Year: 2012

Robots should be capable of interacting in a cooperative and adaptive manner with their human counterparts in open-ended tasks that can change in real-time. An important aspect of the robot behavior will be the ability to acquire new knowledge of the cooperative tasks by observing and interacting with humans. The current research addresses this challenge. We present results from a cooperative human-robot interaction system that has been specifically developed for portability between different humanoid platforms, by abstraction layers at the perceptual and motor interfaces. In the perceptual domain, the resulting system is demonstrated to learn to recognize objects and to recognize actions as sequences of perceptual primitives, and to transfer this learning, and recognition, between different robotic platforms. For execution, composite actions and plans are shown to be learnt on one robot and executed successfully on a different one. Most importantly, the system provides the ability to link actions into shared plans, that form the basis of human-robot cooperation, applying principles from human cognitive development to the domain of robot cognitive systems. © 2009-2011 IEEE.

Aksoy I.,French Institute of Health and Medical Research | Aksoy I.,Stem Cell and Brain Research Institute | Aksoy I.,University of Lyon | Aksoy I.,Genome Institute of Singapore | And 39 more authors.
Nature Communications | Year: 2014

Krüppel-like factors (Klf) 4 and 5 are two closely related members of the Klf family, known to play key roles in cell cycle regulation, somatic cell reprogramming and pluripotency. Here we focus on the functional divergence between Klf4 and Klf5 in the inhibition of mouse embryonic stem (ES) cell differentiation. Using microarrays and chromatin immunoprecipitation coupled to ultra-high-throughput DNA sequencing, we show that Klf4 negatively regulates the expression of endodermal markers in the undifferentiated ES cells, including transcription factors involved in the commitment of pluripotent stem cells to endoderm differentiation. Knockdown of Klf4 enhances differentiation towards visceral and definitive endoderm. In contrast, Klf5 negatively regulates the expression of mesodermal markers, some of which control commitment to the mesoderm lineage, and knockdown of Klf5 specifically enhances differentiation towards mesoderm. We conclude that Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in murine ES cells. © 2014 Macmillan Publishers Limited. All rights reserved.

Daneault V.,University of Montréal | Daneault V.,Center for Advanced Research in Sleep Medicine | Vandewalle G.,University of Montréal | Vandewalle G.,Center for Advanced Research in Sleep Medicine | And 13 more authors.
Journal of Biological Rhythms | Year: 2012

Many nonvisual functions are regulated by light through a photoreceptive system involving melanopsin-expressing retinal ganglion cells that are maximally sensitive to blue light. Several studies have suggested that the ability of light to modulate circadian entrainment and to induce acute effects on melatonin secretion, subjective alertness, and gene expression decreases during aging, particularly for blue light. This could contribute to the documented changes in sleep and circadian regulatory processes with aging. However, age-related modification in the impact of light on steady-state pupil constriction, which regulates the amount of light reaching the retina, is not demonstrated. We measured pupil size in 16 young (22.8 ± 4 years) and 14 older (61 ± 4.4 years) healthy subjects during 45-second exposures to blue (480 nm) and green (550 nm) monochromatic lights at low (7 × 1012 photons/cm2/s), medium (3 × 1013 photons/cm2/s), and high (1014 photons/cm2/s) irradiance levels. Results showed that young subjects had consistently larger pupils than older subjects for dark adaptation and during all light exposures. Steady-state pupil constriction was greater under blue than green light exposure in both age groups and increased with increasing irradiance. Surprisingly, when expressed in relation to baseline pupil size, no significant age-related differences were observed in pupil constriction. The observed reduction in pupil size in older individuals, both in darkness and during light exposure, may reduce retinal illumination and consequently affect nonvisual responses to light. The absence of a significant difference between age groups for relative steady-state pupil constriction suggests that other factors such as tonic, sympathetic control of pupil dilation, rather than light sensitivity per se, account for the observed age difference in pupil size regulation. Compared to other nonvisual functions, the light sensitivity of steady-state pupil constriction appears to remain relatively intact and is not profoundly altered by age. © 2012 The Author(s).

O'Reilly J.X.,University of Oxford | Croxson P.L.,Mount Sinai School of Medicine | Jbabdi S.,University of Oxford | Sallet J.,University of Oxford | And 8 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states.

Gibert G.,French Institute of Health and Medical Research | Gibert G.,Stem Cell and Brain Research Institute | Gibert G.,University of Lyon | Gibert G.,University of Western Sydney | And 2 more authors.
Speech Communication | Year: 2013

Several puppetry techniques have been recently proposed to transfer emotional facial expressions to an avatar from a user's video. Whereas generation of facial expressions may not be sensitive to small tracking errors, generation of speech-related facial movements would be severely impaired. Since incongruent facial movements can drastically influence speech perception, we proposed a more effective method to transfer speech-related facial movements from a user to an avatar. After a facial tracking phase, speech articulatory parameters (controlling the jaw and the lips) were determined from the set of landmark positions. Two additional processes calculated the articulatory parameters which controlled the eyelids and the tongue from the 2D Discrete Cosine Transform coefficients of the eyes and inner mouth images. A speech in noise perception experiment was conducted on 25 participants to evaluate the system. Increase in intelligibility was shown for the avatar and human auditory-visual conditions compared to the avatar and human auditory-only conditions, respectively. Depending on the vocalic context, the results of the avatar auditory-visual presentation were different: all the consonants were better perceived in /a/ vocalic context compared to /i/ and /u/ because of the lack of depth information retrieved from video. This method could be used to accurately animate avatars for hearing impaired people using information technologies and telecommunication. © 2012 Elsevier B.V. All rights reserved.

PubMed | Stem Cell and Brain Research Institute
Type: Journal Article | Journal: Trends in neurosciences | Year: 2010

Anatomical and functional studies of the prefrontal cortex (PFC) have identified multiple PFC subregions. We argue that the PFC is involved in cognitive functions exceeding the sum of specific functions attributed to its subregions. These can be revealed either by lesions of the whole PFC, or more specifically by selective disconnection of the PFC from certain types of information (for example, visual) allowing the investigation of PFC function in toto. Recent studies in macaque monkeys using the latter approach lead to a second conclusion: that the PFC, as a whole, could be fundamentally specialized for representing events that are extended in time. The representation of temporally complex events might underlie PFC involvement in general intelligence, decision-making, and executive function.

PubMed | Stem Cell and Brain Research Institute
Type: Journal Article | Journal: Neuroscience letters | Year: 2010

In order to determine sources and metabolism of melatonin in human cerebrospinal fluid (CSF), melatonin and 6-sulfatoxymelatonin (aMT6S) concentrations were measured in CSF sampled during neurosurgery in both lateral and third ventricles in patients displaying movement disorder (Parkinsons disease, essential tremor, dystonia or dyskinesia) and compared with their plasma levels. Previous determinations in nocturnal urine had showed that the patients displayed melatonin excretion in the normal range, compared with healthy controls matched according to age. A significant difference in melatonin concentration was observed between lateral and third ventricles, with the highest levels in the third ventricle (8.75+/-2.75 pg/ml vs. 3.20+/-0.33 pg/ml, p=0.01). CSF aMT6s levels were similar in both ventricles and of low magnitude, less than 5 pg/ml. They were not correlated with melatonin levels or influenced by the area of sampling. Melatonin levels were significantly higher in third ventricle than in the plasma, whereas there was no difference between plasma and lateral ventricle levels. These findings show that melatonin may enter directly the CSF through the pineal recess in humans. The physiological meaning of these data remains to be elucidated.

PubMed | Technical University of Denmark, University of Washington, Stem cell and Brain Research Institute and University of Oxford
Type: Journal Article | Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience | Year: 2016

Tractography based on diffusion MRI offers the promise of characterizing many aspects of long-distance connectivity in the brain, but requires quantitative validation to assess its strengths and limitations. Here, we evaluate tractographys ability to estimate the presence and strength of connections between areas of macaque neocortex by comparing its results with published data from retrograde tracer injections. Probabilistic tractography was performed on high-quality postmortem diffusion imaging scans from two Old World monkey brains. Tractography connection weights were estimated using a fractional scaling method based on normalized streamline density. We found a correlation between log-transformed tractography and tracer connection weights of r = 0.59, twice that reported in a recent study on the macaque. Using a novel method to estimate interareal connection lengths from tractography streamlines, we regressed out the distance dependence of connection strength and found that the correlation between tractography and tracers remains positive, albeit substantially reduced. Altogether, these observations provide a valuable, data-driven perspective on both the strengths and limitations of tractography for analyzing interareal corticocortical connectivity in nonhuman primates and a framework for assessing future tractography methodological refinements objectively.Tractography based on diffusion MRI has great potential for a variety of applications, including estimation of comprehensive maps of neural connections in the brain (connectomes). Here, we describe methods to assess quantitatively tractographys performance in detecting interareal cortical connections and estimating connection strength by comparing it against published results using neuroanatomical tracers. We found the correlation of tractographys estimated connection strengths versus tracer to be twice that of a previous study. Using a novel method for calculating interareal cortical distances, we show that tractography-based estimates of connection strength have useful predictive power beyond just interareal separation. By freely sharing these methods and datasets, we provide a valuable resource for future studies in cortical connectomics.

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