Glioma is a common type of primary brain tumour, with a strongly invasive potential, often exhibiting non-uniform, highly irregular growth. This makes it difficult to assess the degree of extent of the tumour, hence bringing about a supplementary challenge for the treatment. It is therefore necessary to understand the migratory behaviour of glioma in greater detail. In this paper, we propose a multiscale model for glioma growth and migration. Our model couples the microscale dynamics (reduced to the binding of surface receptors to the surrounding tissue) with a kinetic transport equation for the cell density on the mesoscopic level of individual cells. On the latter scale, we also include the proliferation of tumour cells via effects of interaction with the tissue. An adequate parabolic scaling yields a convection-diffusion-reaction equation, for which the coefficients can be explicitly determined from the information about the tissue obtained by diffusion tensor imaging (DTI). Numerical simulations relying on DTI measurements confirm the biological findings that glioma spread along white matter tracts.

We consider the multiscale model for glioma growth introduced in [19] and extend it to account for therapy effects. Thereby, three treatment strategies involving surgical resection, radio-, and chemotherapy are compared for their efficiency. The chemotherapy relies on inhibiting the binding of cell surface receptors to the surrounding tissue, which impairs both migration and proliferation.

We present a serial design process with associated tools to select parameter values for a posture and locomotion controller for simulation of a robot. The controller is constructed from dynamic neuron and synapse models and simulated with the open-source neuromechanical simulator AnimatLab 2. Each joint has a central pattern generator (CPG), whose neurons possess persistent sodium channels. The CPG rhythmically inhibits motor neurons that control the servomotor's velocity. Sensory information coordinates the joints in the leg into a cohesive stepping motion. The parameter value design process is intended to run on a desktop computer, and has three steps. First, our tool FEEDBACKDESIGN uses classical control methods to find neural and synaptic parameter values that stably and robustly control servomotor output. This method is fast, testing over 100 parameter value variations per minute. Next, our tool CPGDESIGN generates bifurcation diagrams and phase response curves for the CPG model. This reveals neural and synaptic parameter values that produce robust oscillation cycles, whose phase can be rapidly entrained to sensory feedback. It also designs the synaptic conductance of inter-joint pathways. Finally, to understand sensitivity to parameters and how descending commands affect a leg's stepping motion, our tool SIMSCAN runs batches of neuromechanical simulations with specified parameter values, which is useful for searching the parameter space of a complicated simulation. These design tools are demonstrated on a simulation of a robot, but may be applied to neuromechanical animal models or physical robots as well.

Animals dynamically adapt to varying terrain and small perturbations with remarkable ease. These adaptations arise from complex interactions between the environment and biomechanical and neural components of the animal's body and nervous system. Research into mammalian locomotion has resulted in several neural and neuro-mechanical models, some of which have been tested in simulation, but few “synthetic nervous systems” have been implemented in physical hardware models of animal systems. One reason is that the implementation into a physical system is not straightforward. For example, it is difficult to make robotic actuators and sensors that model those in the animal. Therefore, even if the sensorimotor circuits were known in great detail, those parameters would not be applicable and new parameter values must be found for the network in the robotic model of the animal. This manuscript demonstrates an automatic method for setting parameter values in a synthetic nervous system composed of non-spiking leaky integrator neuron models. This method works by first using a model of the system to determine required motor neuron activations to produce stable walking. Parameters in the neural system are then tuned systematically such that it produces similar activations to the desired pattern determined using expected sensory feedback. We demonstrate that the developed method successfully produces adaptive locomotion in the rear legs of a dog-like robot actuated by artificial muscles. Furthermore, the results support the validity of current models of mammalian locomotion. This research will serve as a basis for testing more complex locomotion controllers and for testing specific sensory pathways and biomechanical designs. Additionally, the developed method can be used to automatically adapt the neural controller for different mechanical designs such that it could be used to control different robotic systems.

A dynamical model of an animal’s nervous system, or synthetic nervous system (SNS), is a potentially transformational control method. Due to increasingly detailed data on the connectivity and dynamics of both mammalian and insect nervous systems, controlling a legged robot with an SNS is largely a problem of parameter tuning. Our approach to this problem is to design functional subnetworks that perform specific operations, and then assemble them into larger models of the nervous system. In this paper, we present networks that perform addition, subtraction, multiplication, division, differentiation, and integration of incoming signals. Parameters are set within each subnetwork to produce the desired output by utilizing the operating range of neural activity, R, the gain of the operation, k, and bounds based on biological values. The assembly of large networks from functional subnetworks underpins our recent results with MantisBot.

Starting from a two-scale description involving receptor binding dynamics and a kinetic transport equation for the evolution of the cell density function under velocity reorientations, we deduce macroscopic models for glioma invasion featuring partial differential equations for the mass density and momentum of a population of glioma cells migrating through the anisotropic brain tissue. The proposed first and higher order moment closure methods enable numerical simulations of the kinetic equation. Their performance is then compared to that of the diffusion limit. The approach allows for DTI-based, patient-specific predictions of the tumor extent and its dynamic behavior.

We propose and study a strongly coupled PDE‐ODE‐ODE system modeling cancer cell invasion through a tissue network under the go‐or‐grow hypothesis asserting that cancer cells can either move or proliferate. Hence, our setting features 2 interacting cell populations with their mutual transitions and involves tissue‐dependent degenerate diffusion and haptotaxis for the moving subpopulation. The proliferating cells and the tissue evolution are characterized by way of ODEs for the respective densities. We prove the global existence of weak solutions and illustrate the model behaviour by numerical simulations in a 2‐dimensional setting. The numerical results recover qualitatively the infiltrative patterns observed histologically and moreover allow to establish a qualitative relationship between the structure of the tissue and the expansion of the tumour, thereby paying heed to its heterogeneity.

No abstract