Bridging functional and anatomical neural connectivity through cluster synchronization.

The dynamics of the brain results from the complex interplay of several neural populations and is affected by both the individual dynamics of these areas and their connection structure. Hence, a fundamental challenge is to derive models of the brain that reproduce both structural and functional features measured experimentally. Our work combines neuroimaging data, such as dMRI, which provides information on the structure of the anatomical connectomes, and fMRI, which detects patterns of approximate synchronous activity between brain areas. We employ cluster synchronization as a tool to integrate the imaging data of a subject into a coherent model, which reconciles structural and dynamic information. By using data-driven and model-based approaches, we refine the structural connectivity matrix in agreement with experimentally observed clusters of brain areas that display coherent activity. The proposed approach leverages the assumption of homogeneous brain areas; we show the robustness of this approach when heterogeneity between the brain areas is introduced in the form of noise, parameter mismatches, and connection delays. As a proof of concept, we apply this approach to MRI data of a healthy adult at resting state.

Pinning control of networks: Dimensionality reduction through simultaneous block-diagonalization of matrices.

In this paper, we study the network pinning control problem in the presence of two different types of coupling: (i) node-to-node coupling among the network nodes and (ii) input-to-node coupling from the source node to the "pinned nodes." Previous work has mainly focused on the case that (i) and (ii) are of the same type. We decouple the stability analysis of the target synchronous solution into subproblems of the lowest dimension by using the techniques of simultaneous block diagonalization of matrices. Interestingly, we obtain two different types of blocks, driven and undriven. The overall dimension of the driven blocks is equal to the dimension of an appropriately defined controllable subspace, while all the remaining undriven blocks are scalar. Our main result is a decomposition of the stability problem into four independent sets of equations, which we call quotient controllable, quotient uncontrollable, redundant controllable, and redundant uncontrollable. Our analysis shows that the number and location of the pinned nodes affect the number and the dimension of each set of equations. We also observe that in a large variety of complex networks, the stability of the target synchronous solution is de facto only determined by a single quotient controllable block.

One-way dependent clusters and stability of cluster synchronization in directed networks.

Cluster synchronization in networks of coupled oscillators is the subject of broad interest from the scientific community, with applications ranging from neural to social and animal networks and technological systems. Most of these networks are directed, with flows of information or energy that propagate unidirectionally from given nodes to other nodes. Nevertheless, most of the work on cluster synchronization has focused on undirected networks. Here we characterize cluster synchronization in general directed networks. Our first observation is that, in directed networks, a cluster A of nodes might be one-way dependent on another cluster B: in this case, A may remain synchronized provided that B is stable, but the opposite does not hold. The main contribution of this paper is a method to transform the cluster stability problem in an irreducible form. In this way, we decompose the original problem into subproblems of the lowest dimension, which allows us to immediately detect inter-dependencies among clusters. We apply our analysis to two examples of interest, a human network of violin players executing a musical piece for which directed interactions may be either activated or deactivated by the musicians, and a multilayer neural network with directed layer-to-layer connections.

Delays induced cluster synchronization in chaotic networks.

We study networks of coupled oscillators and analyze the role of coupling delays in determining the emergence of cluster synchronization. Given a network topology and a particular arrangement of the coupling delays over the network connections, different patterns of cluster synchronization may emerge. We focus on a simple ring network of six bidirectionally coupled identical oscillators, for which with two different values of the delays, a total of eight cluster synchronization patterns may emerge, depending on the assignment of the delays to the ring connections. We analyze stability of each of the patterns and find that for large enough coupling strength and specific values of the delays, they can all be stabilized. We construct an experimental ring of six bidirectionally coupled Colpitts oscillators, with delayed connections obtained by coupling the oscillators via RF cables of appropriate length. We find that experimental observations of cluster synchronization are in essential agreement with theoretical predictions. We also verify our theory in a fully connected network of fifty nodes for which connections are randomly assigned to be either undelayed or delayed with a given probability.

Analyzing synchronized clusters in neuron networks.

The presence of synchronized clusters in neuron networks is a hallmark of information transmission and processing. Common approaches to study cluster synchronization in networks of coupled oscillators ground on simplifying assumptions, which often neglect key biological features of neuron networks. Here we propose a general framework to study presence and stability of synchronous clusters in more realistic models of neuron networks, characterized by the presence of delays, different kinds of neurons and synapses. Application of this framework to two examples with different size and features (the directed network of the macaque cerebral cortex and the swim central pattern generator of a mollusc) provides an interpretation key to explain known functional mechanisms emerging from the combination of anatomy and neuron dynamics. The cluster synchronization analysis is carried out also by changing parameters and studying bifurcations. Despite some modeling simplifications in one of the examples, the obtained results are in good agreement with previously reported biological data.

Design Principles for Central Pattern Generators With Preset Rhythms.

This article is concerned with the design of synthetic central pattern generators (CPGs). Biological CPGs are neural circuits that determine a variety of rhythmic activities, including locomotion, in animals. A synthetic CPG is a network of dynamical elements (here called cells) properly coupled by various synapses to emulate rhythms produced by a biological CPG. We focus on CPGs for locomotion of quadrupeds and present our design approach, based on the principles of nonlinear dynamics, bifurcation theory, and parameter optimization. This approach lets us design the synthetic CPG with a set of desired rhythms and switch between them as the parameter representing the control actions from the brain is varied. The developed four-cell CPG can produce four distinct gaits: walk, trot, gallop, and bound, similar to the mouse locomotion. The robustness and adaptability of the network design principles are verified using different cell and synapse models.

Dimensional reduction in networks of non-Markovian spiking neurons: Equivalence of synaptic filtering and heterogeneous propagation delays.

Message passing between components of a distributed physical system is non-instantaneous and contributes to determine the time scales of the emerging collective dynamics. In biological neuron networks this is due in part to local synaptic filtering of exchanged spikes, and in part to the distribution of the axonal transmission delays. How differently these two kinds of communication protocols affect the network dynamics is still an open issue due to the difficulties in dealing with the non-Markovian nature of synaptic transmission. Here, we develop a mean-field dimensional reduction yielding to an effective Markovian dynamics of the population density of the neuronal membrane potential, valid under the hypothesis of small fluctuations of the synaptic current. Within this limit, the resulting theory allows us to prove the formal equivalence between the two transmission mechanisms, holding for any synaptic time scale, integrate-and-fire neuron model, spike emission regimes and for different network states even when the neuron number is finite. The equivalence holds even for larger fluctuations of the synaptic input, if white noise currents are incorporated to model other possible biological features such as ionic channel stochasticity.

Phase analysis method for burst onset prediction.

The response of bursting neurons to fluctuating inputs is usually hard to predict, due to their strong nonlinearity. For the same reason, decoding the injected stimulus from the activity of a bursting neuron is generally difficult. In this paper we propose a method describing (for neuron models) a mechanism of phase coding relating the burst onsets with the phase profile of the input current. This relation suggests that burst onset may provide a way for postsynaptic neurons to track the input phase. Moreover, we define a method of phase decoding to solve the inverse problem and estimate the likelihood of burst onset given the input state. Both methods are presented here in a unified framework, describing a complete coding-decoding procedure. This procedure is tested by using different neuron models, stimulated with different inputs (stochastic, sinusoidal, up, and down states). The results obtained show the efficacy and broad range of application of the proposed methods. Possible applications range from the study of sensory information processing, in which phase-of-firing codes are known to play a crucial role, to clinical applications such as deep brain stimulation, helping to design stimuli in order to trigger or prevent neural bursting.

A mathematical model for the vessel recruitment in coronary microcirculation in the absence of active autoregulation.

This paper proposes a mathematical model for vessel recruitment in the microvascular coronary network. The model is based on microvascular network units (MVNUs), where we define a MVNU as a portion of the microvascular network comprising seven generations of identical, parallel-arranged vessels (upstream arteries, large and small arterioles, capillaries, small and large venules, and downstream veins). The model implements a new mechanism to describe the variation in the number of MVNU in response to sudden variations of the local input pressure. In particular, it describes a recruitment mechanism dependent on distal pressure which operates in the coronary microcirculatory network even in maximally dilated conditions. We apply the model to interpret data from 29 patients who underwent revascularization by percutaneous coronary intervention (PCI). Treated vessels were the left anterior descending coronary artery, the left circumflex and the right coronary artery in 26, 2 and 1 patients, respectively. Following intracoronary adenosine administration, distal coronary pressure and blood flow were 48 ± 18 mmHg and 45 ± 30 ml/min before PCI, respectively, and significantly increased afterwards to 80 ± 17 mmHg and 68 ± 32 ml/min (p<0.001). The model predicts an increase in MVNU number in patients with preserved wall motion in the myocardial region which underwent PCI. On the contrary, a decrease in MVNU number is predicted by the model in patients with regional dysfunction and implies a relatively lower response of maximal flow to revascularization.

Inferring network dynamics and neuron properties from population recordings.

Understanding the computational capabilities of the nervous system means to "identify" its emergent multiscale dynamics. For this purpose, we propose a novel model-driven identification procedure and apply it to sparsely connected populations of excitatory integrate-and-fire neurons with spike frequency adaptation (SFA). Our method does not characterize the system from its microscopic elements in a bottom-up fashion, and does not resort to any linearization. We investigate networks as a whole, inferring their properties from the response dynamics of the instantaneous discharge rate to brief and aspecific supra-threshold stimulations. While several available methods assume generic expressions for the system as a black box, we adopt a mean-field theory for the evolution of the network transparently parameterized by identified elements (such as dynamic timescales), which are in turn non-trivially related to single-neuron properties. In particular, from the elicited transient responses, the input-output gain function of the neurons in the network is extracted and direct links to the microscopic level are made available: indeed, we show how to extract the decay time constant of the SFA, the absolute refractory period and the average synaptic efficacy. In addition and contrary to previous attempts, our method captures the system dynamics across bifurcations separating qualitatively different dynamical regimes. The robustness and the generality of the methodology is tested on controlled simulations, reporting a good agreement between theoretically expected and identified values. The assumptions behind the underlying theoretical framework make the method readily applicable to biological preparations like cultured neuron networks and in vitro brain slices.

Barriers to transport induced by periodic oscillations in a physical model of the human vitreous chamber.

Understanding mixing processes that occur in the human vitreous chamber is of fundamental importance due to the relevant clinical implications in drug delivery treatments of several eye conditions. In this article we rely on experimental observations (which demonstrated that dispersion coefficients largely dominate diffusive coefficients) on a physical model of the human eye to perform an analysis based on Lagrangian trajectories. In particular, we study barriers to transport in a particularly significant two-dimensional section of the eye model by using nonlinear dynamical systems theoretical and numerical tools. Bifurcations in the system dynamics are investigated by varying the main physical parameters of the problem.

Accurate and fast simulation of channel noise in conductance-based model neurons by diffusion approximation.

Stochastic channel gating is the major source of intrinsic neuronal noise whose functional consequences at the microcircuit- and network-levels have been only partly explored. A systematic study of this channel noise in large ensembles of biophysically detailed model neurons calls for the availability of fast numerical methods. In fact, exact techniques employ the microscopic simulation of the random opening and closing of individual ion channels, usually based on Markov models, whose computational loads are prohibitive for next generation massive computer models of the brain. In this work, we operatively define a procedure for translating any Markov model describing voltage- or ligand-gated membrane ion-conductances into an effective stochastic version, whose computer simulation is efficient, without compromising accuracy. Our approximation is based on an improved Langevin-like approach, which employs stochastic differential equations and no Montecarlo methods. As opposed to an earlier proposal recently debated in the literature, our approximation reproduces accurately the statistical properties of the exact microscopic simulations, under a variety of conditions, from spontaneous to evoked response features. In addition, our method is not restricted to the Hodgkin-Huxley sodium and potassium currents and is general for a variety of voltage- and ligand-gated ion currents. As a by-product, the analysis of the properties emerging in exact Markov schemes by standard probability calculus enables us for the first time to analytically identify the sources of inaccuracy of the previous proposal, while providing solid ground for its modification and improvement we present here.

The Hindmarsh-Rose neuron model: bifurcation analysis and piecewise-linear approximations.

This paper provides a global picture of the bifurcation scenario of the Hindmarsh-Rose model. A combination between simulations and numerical continuations is used to unfold the complex bifurcation structure. The bifurcation analysis is carried out by varying two bifurcation parameters and evidence is given that the structure that is found is universal and appears for all combinations of bifurcation parameters. The information about the organizing principles and bifurcation diagrams are then used to compare the dynamics of the model with that of a piecewise-linear approximation, customized for circuit implementation. A good match between the dynamical behaviors of the models is found. These results can be used both to design a circuit implementation of the Hindmarsh-Rose model mimicking the diversity of neural response and as guidelines to predict the behavior of the model as well as its circuit implementation as a function of parameters.

A modular supervised algorithm for vessel segmentation in red-free retinal images.

In this paper, a supervised algorithm for vessel segmentation in red-free images of the human retina is proposed. The algorithm is modular and made up of two fundamental blocks. The optimal values of two algorithm parameters are found out by maximizing proper measures of performances (MOPs) able to evaluate from a quantitative point of view the results provided by the proposed algorithm. The choice of the MOP allows one to tailor the solution to the specific image features to be emphasized. The performances of the algorithm are compared with those of other methods described in the literature. The simulation results show a good trade-off between quality and processing speed times. For instance, in terms of the maximum average accuracy (MAA), K value, and specificity (SP), the best performance outcomes are 0.9587, 0.8069 and 0.9477, respectively.

On the complexity of periodic and nonperiodic behaviors of a hysteresis-based electronic oscillator.

We investigate the families of periodic and nonperiodic behaviors admitted by a hysteresis-based circuit oscillator. The analysis is carried out by combining brute-force simulations with continuation methods. As a result of the analysis, it is shown that the existence of many different periodic solutions and of the chaotic behaviors associated with them is organized by few codimension-2 bifurcation points. This implies the possibility of switching between different periodic solutions by controlling only two bifurcation parameters, which makes the oscillator a possible generator of nontrivial periodic solutions suitable, for instance for actual radiofrequency identification systems applications.