Martin R. Nelson

In this paper, we investigate synchronization patterns and coherence for a network of delayed Wilson–Cowan nodes. To capture information processing across different brain regions, our model incorporates two distinct delays: an intra-nodal delay that reflects the time signals take to travel within a cortical region due to local circuitry and an inter-nodal delay representing the longer communication times associated with white matter connections between brain areas. To investigate the role of network topology, we consider a range of toy network structures as well as the known (macro-scale) cortical structure of the Macaque monkey. We examine how global network dynamics are shaped by a combination of network configuration, coupling strength, and time delays. Our focus lies on two dynamic measures: synchrony and metastability, the latter reflecting the temporal variation of the former, both crucial for the brain’s real-time functionality. Our investigation identifies extensive regions within the system’s parameter space where the synchronized state exhibits transverse instabilities. These instabilities give rise to diverse dynamical behaviors contingent upon the network architecture and the interplay between coupling strength and time delay. While similar complex partially synchronized states existed for all network topologies considered, the cortical network demonstrated time-dependent behaviors, such as phase cluster dynamics, which were absent in the toy network architectures, and which are considered crucial in its ability to orchestrate complex information processing and behavior. Additionally, we illustrate how delays can regulate a cortical network with chaotic local dynamics, thus emphasizing the potential importance of delays in suppressing pathological spreading dynamics.

Macrophages play a wide range of roles in resolving the inflammatory damage that underlies many medical conditions and have the ability to adopt different phenotypes in response to different environmental stimuli. Categorising macrophage phenotypes exactly is a difficult task, and there is disparity in the literature around the optimal nomenclature to describe these phenotypes; however, what is clear is that macrophages can exhibit both pro- and anti-inflammatory behaviours dependent upon their phenotype, rendering mathematical models of the inflammatory response potentially sensitive to their description of the macrophage populations that they incorporate. Many previous models of inflammation include a single macrophage population with both pro- and anti-inflammatory functions. Here, we build upon these existing models to include explicit descriptions of distinct macrophage phenotypes and examine the extent to which this influences the inflammatory dynamics that the models emit. We analyse our models via numerical simulation in MATLAB and dynamical systems analysis in XPPAUT, and show that models that account for distinct macrophage phenotypes separately can offer more realistic steady state solutions than precursor models do (better capturing the anti-inflammatory activity of tissue resident macrophages), as well as oscillatory dynamics not previously observed. Finally, we reflect on the conclusions of our analysis in the context of the ongoing hunt for potential new therapies for inflammatory conditions, highlighting manipulation of macrophage polarisation states as a potential therapeutic target.

The Gray--Scott model is a widely studied autocatalytic model that exhibits a range of interesting pattern formation behavior, as well as a rich structure of dynamics that includes many ideas from ...

Many common medical conditions (such as cancer, arthritis, chronic obstructive pulmonary disease (COPD), and others) are associated with inflammation, and even more so when combined with the effects of ageing and multimorbidity. While the inflammatory response varies in different tissue types, under disease and in response to therapeutic interventions, it has common interactions that occur between immune cells and inflammatory mediators. Understanding these underlying inflammatory mechanisms is key in progressing treatments and therapies for numerous inflammatory conditions. It is now considered that constituent mechanisms of the inflammatory response can be actively manipulated in order to drive resolution of inflammatory damage; particularly, those mechanisms related to the pro-inflammatory role of neutrophils and the anti-inflammatory role of macrophages. In this article, we describe the assembly of a hybrid mathematical model in which the spatial spread of inflammatory mediators is described through partial differential equations, and immune cells (neutrophils and macrophages) are described individually via an agent-based modelling approach. We pay close attention to how immune cells chemotax toward pro-inflammatory mediators, presenting a model for cell chemotaxis that is calibrated against experimentally observed cell trajectories in healthy and COPD-affected scenarios. We illustrate how variations in key model parameters can drive the switch from resolution of inflammation to chronic outcomes, and show that aberrant neutrophil chemotaxis can move an otherwise healthy outcome to one of chronicity. Finally, we reflect on our results in the context of the on-going hunt for new therapeutic interventions.

Understanding structure--function relationships in the brain remains an important challenge in neuroscience. However, whilst structural brain networks are intrinsically directed, due to the prevalence of chemical synapses in the cortex, most studies in network neuroscience represent the brain as an undirected network. Here, we explore the role that directionality plays in shaping transition dynamics of functional brain states. Using a system of Hopfield neural elements with heterogeneous structural connectivity given by different species and parcellations (cat, Caenorhabditis elegans and two macaque networks), we investigate the effect of removing directionality of connections on brain capacity, which we quantify via its ability to store attractor states. In addition to determining large numbers of fixed-point attractor sets, we deploy the recently developed basin stability technique in order to assess the global stability of such brain states, which can be considered a proxy for network state robustness. Our study indicates that not only can directed network topology have a significant effect on the information capacity of connectome-based networks, but it can also impact significantly the domains of attraction of the aforementioned brain states. In particular, we find network modularity to be a key mechanism underlying the formation of neural activity patterns, and moreover, our results suggest that neglecting network directionality has the scope to eliminate states that correlate highly with the directed modular structure of the brain. A numerical analysis of the distribution of attractor states identified a small set of prototypical direction-dependent activity patterns that potentially constitute a `skeleton' of the non-stationary dynamics typically observed in the brain. This study thereby emphasizes the substantial role network directionality can have in shaping the brain's ability to both store and process information.

Understanding the mechanisms that control the body’s response to inflammation is of key importance, due to its involvement in myriad medical conditions, including cancer, arthritis, Alzheimer’s disease and asthma. While resolving inflammation has historically been considered a passive process, since the turn of the century the hunt for novel therapeutic interventions has begun to focus upon active manipulation of constituent mechanisms, particularly involving the roles of apoptosing neutrophils, phagocytosing macrophages and anti-inflammatory mediators. Moreover, there is growing interest in how inflammatory damage can spread spatially due to the motility of inflammatory mediators and immune cells. For example, impaired neutrophil chemotaxis is implicated in causing chronic inflammation under trauma and in ageing, while neutrophil migration is an attractive therapeutic target in ailments such as chronic obstructive pulmonary disease. We extend an existing homogeneous model that captures interactions between inflammatory mediators, neutrophils and macrophages to incorporate spatial behaviour. Through bifurcation analysis and numerical simulation, we show that spatially inhomogeneous outcomes can present close to the switch from bistability to guaranteed resolution in the corresponding homogeneous model. Finally, we show how aberrant spatial mechanisms can play a role in the failure of inflammation to resolve and discuss our results within the broader context of seeking novel inflammatory treatments.