Sustained synchronized neuronal network activity in a human astrocyte co-culture system

Impaired neuronal network function is a hallmark of neurodevelopmental and neurodegenerative disorders such as autism, schizophrenia, and Alzheimer's disease and is typically studied using genetically modified cellular and animal models. Weak predictive capacity and poor translational value of these models urge for better human derived in vitro models. The implementation of human induced pluripotent stem cells (hiPSCs) allows studying pathologies in differentiated disease-relevant and patient-derived neuronal cells. However, the differentiation process and growth conditions of hiPSC-derived neurons are non-trivial. In order to study neuronal network formation and (mal) function in a fully humanized system, we have established an in vitro co-culture model of hiPSC-derived cortical neurons and human primary astrocytes that recapitulates neuronal network synchronization and connectivity within three to four weeks after final plating. Live cell calcium imaging, electrophysiology and high content image analyses revealed an increased maturation of network functionality and synchronicity over time for co-cultures compared to neuronal monocultures. The cells express GABAergic and glutamatergic markers and respond to inhibitors of both neurotransmitter pathways in a functional assay. The combination of this co-culture model with quantitative imaging of network morphofunction is amenable to high throughput screening for lead discovery and drug optimization for neurological diseases

A blind deconvolution approach to recover effective connectivity brain networks from resting state fMRI data

A great improvement to the insight on brain function that we can get from fMRI data can come from effective connectivity analysis, in which the flow of information between even remote brain regions is inferred by the parameters of a predictive dynamical model. As opposed to biologically inspired models, some techniques as Granger causality (GC) are purely data-driven and rely on statistical prediction and temporal precedence. While powerful and widely applicable, this approach could suffer from two main limitations when applied to BOLD fMRI data: confounding effect of hemodynamic response function (HRF) and conditioning to a large number of variables in presence of short time series. For task-related fMRI, neural population dynamics can be captured by modeling signal dynamics with explicit exogenous inputs; for resting-state fMRI on the other hand, the absence of explicit inputs makes this task more difficult, unless relying on some specific prior physiological hypothesis. In order to overcome these issues and to allow a more general approach, here we present a simple and novel blind-deconvolution technique for BOLD-fMRI signal. Coming to the second limitation, a fully multivariate conditioning with short and noisy data leads to computational problems due to overfitting. Furthermore, conceptual issues arise in presence of redundancy. We thus apply partial conditioning to a limited subset of variables in the framework of information theory, as recently proposed. Mixing these two improvements we compare the differences between BOLD and deconvolved BOLD level effective networks and draw some conclusions

Brain covariance selection: better individual functional connectivity models using population prior

Spontaneous brain activity, as observed in functional neuroimaging, has been shown to display reproducible structure that expresses brain architecture and carries markers of brain pathologies. An important view of modern neuroscience is that such large-scale structure of coherent activity reflects modularity properties of brain connectivity graphs. However, to date, there has been no demonstration that the limited and noisy data available in spontaneous activity observations could be used to learn full-brain probabilistic models that generalize to new data. Learning such models entails two main challenges: i) modeling full brain connectivity is a difficult estimation problem that faces the curse of dimensionality and ii) variability between subjects, coupled with the variability of functional signals between experimental runs, makes the use of multiple datasets challenging. We describe subject-level brain functional connectivity structure as a multivariate Gaussian process and introduce a new strategy to estimate it from group data, by imposing a common structure on the graphical model in the population. We show that individual models learned from functional Magnetic Resonance Imaging (fMRI) data using this population prior generalize better to unseen data than models based on alternative regularization schemes. To our knowledge, this is the first report of a cross-validated model of spontaneous brain activity. Finally, we use the estimated graphical model to explore the large-scale characteristics of functional architecture and show for the first time that known cognitive networks appear as the integrated communities of functional connectivity graph.Comment: in Advances in Neural Information Processing Systems, Vancouver : Canada (2010

Neural Avalanches at the Critical Point between Replay and Non-Replay of Spatiotemporal Patterns

We model spontaneous cortical activity with a network of coupled spiking units, in which multiple spatio-temporal patterns are stored as dynamical attractors. We introduce an order parameter, which measures the overlap (similarity) between the activity of the network and the stored patterns. We find that, depending on the excitability of the network, different working regimes are possible. For high excitability, the dynamical attractors are stable, and a collective activity that replays one of the stored patterns emerges spontaneously, while for low excitability, no replay is induced. Between these two regimes, there is a critical region in which the dynamical attractors are unstable, and intermittent short replays are induced by noise. At the critical spiking threshold, the order parameter goes from zero to one, and its fluctuations are maximized, as expected for a phase transition (and as observed in recent experimental results in the brain). Notably, in this critical region, the avalanche size and duration distributions follow power laws. Critical exponents are consistent with a scaling relationship observed recently in neural avalanches measurements. In conclusion, our simple model suggests that avalanche power laws in cortical spontaneous activity may be the effect of a network at the critical point between the replay and non-replay of spatio-temporal patterns

Anticipatory Semantic Processes

Why anticipatory processes correspond to cognitive abilities of living systems? To be adapted to an environment, behaviors need at least i) internal representations of events occurring in the external environment; and ii) internal anticipations of possible events to occur in the external environment. Interactions of these two opposite but complementary cognitive properties lead to various patterns of experimental data on semantic processing. How to investigate dynamic semantic processes? Experimental studies in cognitive psychology offer several interests such as: i) the control of the semantic environment such as words embedded in sentences; ii) the methodological tools allowing the observation of anticipations and adapted oculomotor behavior during reading; and iii) the analyze of different anticipatory processes within the theoretical framework of semantic processing. What are the different types of semantic anticipations? Experimental data show that semantic anticipatory processes involve i) the coding in memory of sequences of words occurring in textual environments; ii) the anticipation of possible future words from currently perceived words; and iii) the selection of anticipated words as a function of the sequences of perceived words, achieved by anticipatory activations and inhibitory selection processes. How to modelize anticipatory semantic processes? Localist or distributed neural networks models can account for some types of semantic processes, anticipatory or not. Attractor neural networks coding temporal sequences are presented as good candidate for modeling anticipatory semantic processes, according to specific properties of the human brain such as i) auto-associative memory; ii) learning and memorization of sequences of patterns; and iii) anticipation of memorized patterns from previously perceived patterns

Detection of subthreshold pulses in neurons with channel noise

Neurons are subject to various kinds of noise. In addition to synaptic noise, the stochastic opening and closing of ion channels represents an intrinsic source of noise that affects the signal processing properties of the neuron. In this paper, we studied the response of a stochastic Hodgkin-Huxley neuron to transient input subthreshold pulses. It was found that the average response time decreases but variance increases as the amplitude of channel noise increases. In the case of single pulse detection, we show that channel noise enables one neuron to detect the subthreshold signals and an optimal membrane area (or channel noise intensity) exists for a single neuron to achieve optimal performance. However, the detection ability of a single neuron is limited by large errors. Here, we test a simple neuronal network that can enhance the pulse detecting abilities of neurons and find dozens of neurons can perfectly detect subthreshold pulses. The phenomenon of intrinsic stochastic resonance is also found both at the level of single neurons and at the level of networks. At the network level, the detection ability of networks can be optimized for the number of neurons comprising the network.Comment: 14 pages, 9 figure

Stimulus sensitivity of a spiking neural network model

Some recent papers relate the criticality of complex systems to their maximal capacity of information processing. In the present paper, we consider high dimensional point processes, known as age-dependent Hawkes processes, which have been used to model spiking neural networks. Using mean-field approximation, the response of the network to a stimulus is computed and we provide a notion of stimulus sensitivity. It appears that the maximal sensitivity is achieved in the sub-critical regime, yet almost critical for a range of biologically relevant parameters

Neuronal Synchronization Can Control the Energy Efficiency of Inter-Spike Interval Coding

The role of synchronous firing in sensory coding and cognition remains controversial. While studies, focusing on its mechanistic consequences in attentional tasks, suggest that synchronization dynamically boosts sensory processing, others failed to find significant synchronization levels in such tasks. We attempt to understand both lines of evidence within a coherent theoretical framework. We conceptualize synchronization as an independent control parameter to study how the postsynaptic neuron transmits the average firing activity of a presynaptic population, in the presence of synchronization. We apply the Berger-Levy theory of energy efficient information transmission to interpret simulations of a Hodgkin-Huxley-type postsynaptic neuron model, where we varied the firing rate and synchronization level in the presynaptic population independently. We find that for a fixed presynaptic firing rate the simulated postsynaptic interspike interval distribution depends on the synchronization level and is well-described by a generalized extreme value distribution. For synchronization levels of 15% to 50%, we find that the optimal distribution of presynaptic firing rate, maximizing the mutual information per unit cost, is maximized at ~30% synchronization level. These results suggest that the statistics and energy efficiency of neuronal communication channels, through which the input rate is communicated, can be dynamically adapted by the synchronization level.Comment: 47 pages, 14 figures, 2 Table