Institut Pasteur de Paris
Neuroscience
Filopodia are dynamic, finger-like plasma membrane protrusions that sense the mechanical and chemical surroundings of the cell. Here, we show in epithelial cells that the dynamics of filopodial extension and retraction are determined by... more
Filopodia are dynamic, finger-like plasma membrane protrusions that sense the mechanical and chemical surroundings of the cell. Here, we show in epithelial cells that the dynamics of filopodial extension and retraction are determined by the difference between the actin polymerization rate at the tip and the retrograde flow at the base of the filopodium. Adhesion of a bead to the filopodial tip locally reduces actin polymerization and leads to retraction via retrograde flow, reminiscent of a process used by pathogens to invade cells. Using optical tweezers, we show that filopodial retraction occurs at a constant speed against counteracting forces up to 50 pN. Our measurements point toward retrograde flow in the cortex together with frictional coupling between the filopodial and cortical actin networks as the main retraction-force generator for filopodia. The force exerted by filopodial retraction, however, is limited by the connection between filopodial actin filaments and the membrane at the tip. Upon mechanical rupture of the tip connection, filopodia exert a passive retraction force of 15 pN via their plasma membrane. Transient reconnection at the tip allows filopodia to continuously probe their surroundings in a load-and-fail manner within a well-defined force range.
Empirical temporal networks display strong heterogeneities in their dynamics, which profoundly affect processes taking place on these networks, such as rumor and epidemic spreading. Despite the recent wealth of data on temporal networks,... more
Empirical temporal networks display strong heterogeneities in their dynamics, which profoundly affect processes taking place on these networks, such as rumor and epidemic spreading. Despite the recent wealth of data on temporal networks, little work has been devoted to the understanding of how such heterogeneities can emerge from microscopic mechanisms at the level of nodes and links. Here we show that long-term memory effects are present in the creation and disappearance of links in empirical networks. We thus consider a simple generative modeling framework for temporal networks able to incorporate these memory mechanisms. This allows us to study separately the role of each of these mechanisms in the emergence of heterogeneous network dynamics. In particular, we show analytically and numerically how heterogeneous distributions of contact durations, of intercontact durations, and of numbers of contacts per link emerge. We also study the individual effect of heterogeneities on dynamical processes, such as the paradigmatic susceptible-infected epidemic spreading model. Our results confirm in particular the crucial role of the distributions of intercontact durations and of the numbers of contacts per link.
Amplitude- and frequency-modulated waves of Ca(2+) ions transmit information inside cells. Reactive Oxygen Species (ROS), specifically hydrogen peroxide, have been proposed to have a similar role in plant cells. We consider the... more
Amplitude- and frequency-modulated waves of Ca(2+) ions transmit information inside cells. Reactive Oxygen Species (ROS), specifically hydrogen peroxide, have been proposed to have a similar role in plant cells. We consider the feasibility of such an intracellular communication system in view of the physical and biochemical conditions in plant cells. As model system, we use a H(2)O(2) signal originating at the plasma membrane (PM) and spreading through the cytosol. We consider two maximally simple types of signals, isolated pulses and harmonic oscillations. First we consider the basic limits on such signals as regards signal origin, frequency, amplitude, and distance. Then we establish the impact of ROS-removing enzymes on the ability of H(2)O(2) to transmit signals. Finally, we consider to what extent cytoplasmic streaming distorts signals. This modeling allows us to predict the conditions under which diffusion-mediated signaling is possible. We show that purely diffusive transmission of intracellular information by H(2)O(2) over a distance of 1 μm (typical distance between organelles, which may function as relay stations) is possible at frequencies well above 1 Hz, which is the highest frequency observed experimentally. This allows both frequency and amplitude modulation of the signal. Signaling over a distance of 10 μm (typical distance between the PM and the nucleus) may be possible, but requires high signal amplitudes or, equivalently, a very low detection threshold. Furthermore, at this longer distance a high rate of enzymatic degradation is required to make signaling at frequencies above 0.1 Hz possible. In either case, cytoplasmic streaming does not seriously disturb signals. We conclude that although purely diffusion-mediated signaling without relaying stations is theoretically possible, it is unlikely to work in practice, since it requires a much faster enzymatic degradation and a much lower cellular background concentration of H(2)O(2) than observed experimentally.
- by Henrik Flyvbjerg and +1
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ABSTRACT Empirical data on contacts between individuals in social contexts play an important role in the information of models describing human behavior and how epidemics spread in populations. Here, we analyze data on face-to-face... more
ABSTRACT Empirical data on contacts between individuals in social contexts play an important role in the information of models describing human behavior and how epidemics spread in populations. Here, we analyze data on face-to-face contacts collected in an office building. The statistical properties of contacts are similar to other social situations, but important differences are observed in the contact network structure. In particular, the contact network is strongly shaped by the organization of the offices in departments, which has consequences in the design of accurate agent-based models of epidemic spread. We then consider the contact network as a potential substrate for infectious disease spread and show that its sparsity tends to prevent outbreaks of fast-spreading epidemics. Moreover, we define three typical behaviors according to the fraction $f$ of links each individual shares outside its own department: residents, wanderers and linkers. Linkers ($f\sim 50%$) act as bridges in the network and have large betweenness centralities. Thus, a vaccination strategy targeting linkers efficiently prevents large outbreaks. As such a behavior may be spotted \emph{a priori} in the offices' organization or from surveys, without the full knowledge of the time-resolved contact network, this result might help the design of efficient, low-cost vaccination or social-distancing strategies.
- by Christian L. Vestergaard and +2
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- Network science
Molecular motors are responsible for numerous cellular processes from cargo transport to heart contraction. Their interactions with other cellular components are often transient and exhibit kinetics that depend on load. Here, we measure... more
Molecular motors are responsible for numerous cellular processes from cargo transport to heart contraction. Their interactions with other cellular components are often transient and exhibit kinetics that depend on load. Here, we measure such interactions using 'harmonic force spectroscopy'. In this method, harmonic oscillation of the sample stage of a laser trap immediately, automatically and randomly applies sinusoidally varying loads to a single motor molecule interacting with a single track along which it moves. The experimental protocol and the data analysis are simple, fast and efficient. The protocol accumulates statistics fast enough to deliver single-molecule results from single-molecule experiments. We demonstrate the method's performance by measuring the force-dependent kinetics of individual human β-cardiac myosin molecules interacting with an actin filament at physiological ATP concentration. We show that a molecule's ADP release rate depends exponentiall...
Data describing human interactions often suffer from incomplete sampling of the underlying population. As a consequence, the study of contagion processes using data-driven models can lead to a severe underestimation of the epidemic risk.... more
Data describing human interactions often suffer from incomplete sampling of the underlying population. As a consequence, the study of contagion processes using data-driven models can lead to a severe underestimation of the epidemic risk. Here we present a systematic method to alleviate this issue and obtain a better estimation of the risk in the context of epidemic models informed by high-resolution time-resolved contact data. We consider several such data sets collected in various contexts and perform controlled resampling experiments. We show how the statistical information contained in the resampled data can be used to build a series of surrogate versions of the unknown contacts. We simulate epidemic processes on the resulting reconstructed data sets and show that it is possible to obtain good estimates of the outcome of simulations performed using the complete data set. We discuss limitations and potential improvements of our method.
Stochastic simulations are one of the cornerstones of the analysis of dynamical processes on complex networks, and are often the only accessible way to explore their behavior. The development of fast algorithms is paramount to allow... more
Stochastic simulations are one of the cornerstones of the analysis of dynamical processes on complex networks, and are often the only accessible way to explore their behavior. The development of fast algorithms is paramount to allow large-scale simulations. The Gillespie algorithm can be used for fast simulation of stochastic processes, and variants of it have been applied to simulate dynamical processes on static networks. However, its adaptation to temporal networks remains non-trivial. We here present a temporal Gillespie algorithm that solves this problem. Our method is applicable to general Poisson (constant-rate) processes on temporal networks, stochastically exact, and up to multiple orders of magnitude faster than traditional simulation schemes based on rejection sampling. We also show how it can be extended to simulate non-Markovian processes. The algorithm is easily applicable in practice, and as an illustration we detail how to simulate both Poissonian and non-Markovian m...
Transition state theory (TST) provides a simple interpretation of many thermally activated processes. It applies successfully on timescales and length scales that differ several orders of magnitude: to chemical reactions, breaking of... more
Transition state theory (TST) provides a simple interpretation of many thermally activated processes. It applies successfully on timescales and length scales that differ several orders of magnitude: to chemical reactions, breaking of chemical bonds, unfolding of proteins and RNA structures and polymers crossing entropic barriers. Here we apply TST to out-of-equilibrium transport through confined environments: the thermally activated translocation of single DNA molecules over an entropic barrier helped by an external force field. Reaction pathways are effectively one dimensional and so long that they are observable in a microscope. Reaction rates are so slow that transitions are recorded on video. We find sharp transition states that are independent of the applied force, similar to chemical bond rupture, as well as transition states that change location on the reaction pathway with the strength of the applied force. The states of equilibrium and transition are separated by micrometres as compared with angstroms/nanometres for chemical bonds.
During social interaction, both participants are continuously active, each modifying their own actions in response to the continuously changing actions of the partner. This continuous mutual adaptation results in interactional synchrony... more
During social interaction, both participants are continuously active, each modifying their own actions in response to the continuously changing actions of the partner. This continuous mutual adaptation results in interactional synchrony to which both members contribute. Freely exchanging the role of imitator and model is a well-framed example of interactional synchrony resulting from a mutual behavioral negotiation. How the participants' brain activity underlies this process is currently a question that hyperscanning recordings allow us to explore. In particular, it remains largely unknown to what extent oscillatory synchronization could emerge between two brains during social interaction. To explore this issue, 18 participants paired as 9 dyads were recorded with dual-video and dual-EEG setups while they were engaged in spontaneous imitation of hand movements. We measured interactional synchrony and the turn-taking between model and imitator. We discovered by the use of nonlinear techniques that states of interactional synchrony correlate with the emergence of an interbrain synchronizing network in the alpha-mu band between the right centroparietal regions. These regions have been suggested to play a pivotal role in social interaction. Here, they acted symmetrically as key functional hubs in the interindividual brainweb. Additionally, neural synchronization became asymmetrical in the higher frequency bands possibly reflecting a top-down modulation of the roles of model and imitator in the ongoing interaction.
Recently, the neuroscience field took a particular interest in the use of a neuroimaging technique called ‘hyperscanning’. This new technique consists in the simultaneous recording of the hemodynamic or neuroelectric activities of... more
Recently, the neuroscience field took a particular interest in the use of a neuroimaging technique called ‘hyperscanning’. This new technique consists in the simultaneous recording of the hemodynamic or neuroelectric activities of multiple subjects. Behind this small technical step lays a giant methodological leap. Groundbreaking insight in the understanding of social cognition shall be achieved if the right paradigms are implemented. A growing number of studies demonstrate the potential of this recent technique. In this paper, we will focus on current issues and future perspectives of brain studies using hyperscanning. We will also add to this review two studies initiated by Line Garnero. These studies will illustrate the promising possibilities offered by hyperscanning through two different key phenomena pertaining to social interaction: gesture imitation and joint attention.
Recent work from our interdisciplinary research group has revealed the emergence of inter-brain synchronization across multiple frequency bands during social interaction.1 Our findings result from the close collaboration between experts... more
Recent work from our interdisciplinary research group has revealed the emergence of inter-brain synchronization across multiple frequency bands during social interaction.1 Our findings result from the close collaboration between experts who study neural dynamics and developmental psychology. The initial aim of the collaboration was to combine knowledge from these two fields in order to move from a classical one-brain neuroscience towards a novel two-body approach. A new technique called hyperscanning has made it possible to study the neural activity of two individuals simultaneously. However, this advanced methodology was not sufficient in itself. What remained to be found was a way to promote real-time reciprocal social interaction between two individuals during brain recording and analyze the neural and behavioral phenomenon from an inter-individual perspective. Approaches used in infancy research to study nonverbal communication and coordination, between a mother and her child for example, have so far been poorly applied to neuroimaging experiments. We thus adapted an ecological two-body experiment inspired by the use of spontaneous imitation in preverbal infants. Numerous methodological and theoretical problems had to be overcome, ranging from the choice of a common time-unit for behavioral and brain recordings to the creation of algorithms for data processing between distant brain regions in different brains. This article will discuss the underlying issues and perspectives involved in elucidating the pathway from individual to social theories of cognition.
Addendum to: Dumas G, Nadel J, Soussignan R, Martinerie J, Garnero L. Inter-brain synchronization during social interaction. PLoS One 2010; 5:278-88.
Addendum to: Dumas G, Nadel J, Soussignan R, Martinerie J, Garnero L. Inter-brain synchronization during social interaction. PLoS One 2010; 5:278-88.
Brain correlates of the sense of agency have recently received increased attention. However, the explorations remain largely restricted to the study of brains in isolation. The prototypical paradigm used so far consists of manipulating... more
Brain correlates of the sense of agency have recently received increased attention. However, the explorations remain largely restricted to the study of brains in isolation. The prototypical paradigm used so far consists of manipulating visual perception of own action while asking the subject to draw a distinction between self- versus externally caused action. However, the recent definition of agency as a multifactorial phenomenon combining bottom-up and top-down processes suggests the exploration of more complex situations. Notably there is a need of accounting for the dynamics of agency in a two-body context where we often experience the double faceted question of who is at the origin of what in an ongoing interaction. In a dyadic context of role switching indeed, each partner can feel body ownership, share a sense of agency and altogether alternate an ascription of the primacy of action to self and to other. To explore the brain correlates of these different aspects of agency, we recorded with dual EEG and video set-ups 22 subjects interacting via spontaneous versus induced imitation (II) of hand movements. The differences between the two conditions lie in the fact that the roles are either externally attributed (induced condition) or result from a negotiation between subjects (spontaneous condition). Results demonstrate dissociations between self- and other-ascription of action primacy in delta, alpha and beta frequency bands during the condition of II. By contrast a similar increase in the low gamma frequency band (38–47 Hz) was observed over the centro-parietal regions for the two roles in spontaneous imitation (SI). Taken together, the results highlight the different brain correlates of agency at play during live interactions.
Recent development in diffusion spectrum brain imaging combined to functional simulation has the potential to further our understanding of how structure and dynamics are intertwined in the human brain. At the intra-individual scale,... more
Recent development in diffusion spectrum brain imaging combined to functional simulation has the potential to further our understanding of how structure and dynamics are intertwined in the human brain. At the intra-individual scale, neurocomputational models have already started to uncover how the human connectome constrains the coordination of brain activity across distributed brain regions. In parallel, at the inter-individual scale, nascent social neuroscience provides a new dynamical vista of the coupling between two embodied cognitive agents. Using EEG hyperscanning to record simultaneously the brain activities of subjects during their ongoing interaction, we have previously demonstrated that behavioral synchrony correlates with the emergence of inter-brain synchronization. However, the functional meaning of such synchronization remains to be specified. Here, we use a biophysical model to quantify to what extent inter-brain synchronizations are related to the anatomical and functional similarity of the two brains in interaction. Pairs of interacting brains were numerically simulated and compared to real data. Results show a potential dynamical property of the human connectome to facilitate inter-individual synchronizations and thus may partly account for our propensity to generate dynamical couplings with others.
Since 2002, a new neuroimaging technique called hyperscanning allows to record several participants simultaneously and thus to study social interaction in a reciprocal and spontaneous social context. Meanwhile, neurodynamics and... more
Since 2002, a new neuroimaging technique called hyperscanning allows to record several participants simultaneously and thus to study social interaction in a reciprocal and spontaneous social context. Meanwhile, neurodynamics and sensorimotor theories suggested to understand social interaction in a more holistic approach by considering the two interacting individuals as a single system, and giving equal importance to behavior and brain activity.
This thesis presents the study of pairs of participants recorded simultaneously during spontaneous imitation of the movement of their hands, by a dual-video combined with a hyperscanning-EEG setup. A fine grained video analysis identified the episodes of interactional synchrony and imitation, thus allowing the neurodynamic characterization of various aspects of the interaction, both at the inter- and intra-individual. The first study showed that episodes of interactional synchrony were accompanied by the emergence of inter-brain phase synchronizations in several frequency bands. The second study showed a neural differentiation between self- and other-attribution of action primacy, and found a signature of the co-ownership of the action in both partners during the spontaneous imitation. The third study validated the experimental measurements with biophysical simulations of pairs of human brains. It also showed the effects of anatomical connectivity on intra-individual neural dynamics and the facilitation of the inter-individual sensorimotor coupling.
This thesis presents the study of pairs of participants recorded simultaneously during spontaneous imitation of the movement of their hands, by a dual-video combined with a hyperscanning-EEG setup. A fine grained video analysis identified the episodes of interactional synchrony and imitation, thus allowing the neurodynamic characterization of various aspects of the interaction, both at the inter- and intra-individual. The first study showed that episodes of interactional synchrony were accompanied by the emergence of inter-brain phase synchronizations in several frequency bands. The second study showed a neural differentiation between self- and other-attribution of action primacy, and found a signature of the co-ownership of the action in both partners during the spontaneous imitation. The third study validated the experimental measurements with biophysical simulations of pairs of human brains. It also showed the effects of anatomical connectivity on intra-individual neural dynamics and the facilitation of the inter-individual sensorimotor coupling.
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