Monostability and multistability of genetic regulatory networks with different types of regulation functions

The official published version of the article can be found at the link below.Monostability and multistability are proven to be two important topics in synthesis biology and system biology. In this paper, both monostability and multistability are analyzed in a unified framework by applying control theory and mathematical tools. The genetic regulatory networks (GRNs) with multiple time-varying delays and different types of regulation functions are considered. By putting forward a general sector-like regulation function and utilizing up-to-date techniques, a novel Lyapunov–Krasovskii functional is introduced for achieving delay dependence to ensure less conservatism. A new condition is then proposed for the general stability of a GRN in the form of linear matrix inequalities (LMIs) that are dependent on the upper and lower bounds of the delays. Our general stability conditions are applicable to several frequently used regulation functions. It is shown that the existing results for monostability of GRNs are special cases of our main results. Five examples are employed to illustrate the applicability and usefulness of the developed theoretical results.This work was supported in part by the Biotechnology and Biological Sciences Research Council (BBSRC) of the U.K. under Grant BB/C506264/1, the Royal Society of the U.K., the National Natural Science Foundation of China under Grants 60504008 and 60804028, the Program for New Century Excellent Talents in Universities of China, and the Alexander von Humboldt Foundation of Germany

Clustering behaviour in networks with time delayed all-to-all coupling

Networks of coupled oscillators arise in a variety of areas. Clustering is a type of oscillatory network behavior where elements of a network segregate into groups. Elements within a group oscillate synchronously, while elements in different groups oscillate with a fixed phase difference. In this thesis, we study networks of N identical oscillators with time delayed, global circulant coupling with two approaches. We first use the theory of weakly coupled oscillators to reduce the system of delay differential equations to a phase model where the time delay enters as a phase shift. We use the phase model to determine model independent existence and stability results for symmetric cluster solutions. We show that the presence of the time delay can lead to the coexistence of multiple stable clustering solutions. We then perform stability and bifurcation analysis to the original system of delay differential equations with symmetry. We first study the existence of Hopf bifurcations induced by coupling time delay, and then use symmetric Hopf bifurcation theory to determine how these bifurcations lead to different patterns of symmetric cluster oscillations. We apply our results to two specfi c examples: a network of FitzHugh-Nagumo neurons with diffusive coupling and a network of Morris-Lecar neurons with synaptic coupling. In the case studies, we show how time delays in the coupling between neurons can give rise to switching between different stable cluster solutions, coexistence of multiple stable cluster solutions and solutions with multiple frequencies

The Dynamic Brain: From Spiking Neurons to Neural Masses and Cortical Fields

The cortex is a complex system, characterized by its dynamics and architecture, which underlie many functions such as action, perception, learning, language, and cognition. Its structural architecture has been studied for more than a hundred years; however, its dynamics have been addressed much less thoroughly. In this paper, we review and integrate, in a unifying framework, a variety of computational approaches that have been used to characterize the dynamics of the cortex, as evidenced at different levels of measurement. Computational models at different space–time scales help us understand the fundamental mechanisms that underpin neural processes and relate these processes to neuroscience data. Modeling at the single neuron level is necessary because this is the level at which information is exchanged between the computing elements of the brain; the neurons. Mesoscopic models tell us how neural elements interact to yield emergent behavior at the level of microcolumns and cortical columns. Macroscopic models can inform us about whole brain dynamics and interactions between large-scale neural systems such as cortical regions, the thalamus, and brain stem. Each level of description relates uniquely to neuroscience data, from single-unit recordings, through local field potentials to functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), and magnetoencephalogram (MEG). Models of the cortex can establish which types of large-scale neuronal networks can perform computations and characterize their emergent properties. Mean-field and related formulations of dynamics also play an essential and complementary role as forward models that can be inverted given empirical data. This makes dynamic models critical in integrating theory and experiments. We argue that elaborating principled and informed models is a prerequisite for grounding empirical neuroscience in a cogent theoretical framework, commensurate with the achievements in the physical sciences

Mathematical frameworks for oscillatory network dynamics in neuroscience

The tools of weakly coupled phase oscillator theory have had a profound impact on the neuroscience community, providing insight into a variety of network behaviours ranging from central pattern generation to synchronisation, as well as predicting novel network states such as chimeras. However, there are many instances where this theory is expected to break down, say in the presence of strong coupling, or must be carefully interpreted, as in the presence of stochastic forcing. There are also surprises in the dynamical complexity of the attractors that can robustly appear—for example, heteroclinic network attractors. In this review we present a set of mathemat- ical tools that are suitable for addressing the dynamics of oscillatory neural networks, broadening from a standard phase oscillator perspective to provide a practical frame- work for further successful applications of mathematics to understanding network dynamics in neuroscience

Hierarchical heterogeneity across human cortex shapes large-scale neural dynamics

The large-scale organization of dynamical neural activity across cortex emerges through long-range interactions among local circuits. We hypothesized that large-scale dynamics are also shaped by heterogeneity of intrinsic local properties across cortical areas. One key axis along which microcircuit properties are specialized relates to hierarchical levels of cortical organization. We developed a large-scale dynamical circuit model of human cortex that incorporates heterogeneity of local synaptic strengths, following a hierarchical axis inferred from MRI-derived T1w/T2w mapping, and fit the model using multimodal neuroimaging data. We found that incorporating hierarchical heterogeneity substantially improves the model fit to fMRI-measured resting-state functional connectivity and captures sensory-association organization of multiple fMRI features. The model predicts hierarchically organized high-frequency spectral power, which we tested with resting-state magnetoencephalography. These findings suggest circuit-level mechanisms linking spatiotemporal levels of analysis and highlight the importance of local properties and their hierarchical specialization on the large-scale organization of human cortical dynamics