Towards an optimised deep brain stimulation using a large-scale computational network and realistic volume conductor model.

Objective. Constructing a theoretical framework to improve deep brain stimulation (DBS) based on the neuronal spatiotemporal patterns of the stimulation-affected areas constitutes a primary target.Approach. We develop a large-scale biophysical network, paired with a realistic volume conductor model, to estimate theoretically efficacious stimulation protocols. Based on previously published anatomically defined structural connectivity, a biophysical basal ganglia-thalamo-cortical neuronal network is constructed using Hodgkin-Huxley dynamics. We define a new biomarker describing the thalamic spatiotemporal activity as a ratio of spiking vs. burst firing. The per cent activation of the different pathways is adapted in the simulation to minimise the differences of the biomarker with respect to its value under healthy conditions.Main results.This neuronal network reproduces spatiotemporal patterns that emerge in Parkinson's disease. Simulations of the fibre per cent activation for the defined biomarker propose desensitisation of pallido-thalamic synaptic efficacy, induced by high-frequency signals, as one possible crucial mechanism for DBS action. Based on this activation, we define both an optimal electrode position and stimulation protocol using pathway activation modelling.Significance. A key advantage of this research is that it combines different approaches, i.e. the spatiotemporal pattern with the electric field and axonal response modelling, to compute the optimal DBS protocol. By correlating the inherent network dynamics with the activation of white matter fibres, we obtain new insights into the DBS therapeutic action.

Optimal vaccine roll-out strategies including social distancing for pandemics.

Non-pharmacological interventions (NPIs), principally social distancing, in combination with effective vaccines, aspire to develop a protective immunity shield against pandemics and particularly against the COVID-19 pandemic. In this study, an agent-based network model with small-world topology is employed to find optimal policies against pandemics, including social distancing and vaccination strategies. The agents' states are characterized by a variation of the SEIR model (susceptible, exposed, infected, recovered). To explore optimal policies, an equation-free method is proposed to solve the inverse problem of calibrating an agent's infection rate with respect to the vaccination efficacy. The results show that prioritizing the first vaccine dose in combination with mild social restrictions, is sufficient to control the pandemic, with respect to the number of deaths. Moreover, for the same mild number of social contacts, we find an optimal vaccination ratio of 0.85 between older people of ages > 65 compared to younger ones.

Deep brain stimulation for movement disorder treatment: exploring frequency-dependent efficacy in a computational network model.

A large-scale computational model of the basal ganglia network and thalamus is proposed to describe movement disorders and treatment effects of deep brain stimulation (DBS). The model of this complex network considers three areas of the basal ganglia region: the subthalamic nucleus (STN) as target area of DBS, the globus pallidus, both pars externa and pars interna (GPe-GPi), and the thalamus. Parkinsonian conditions are simulated by assuming reduced dopaminergic input and corresponding pronounced inhibitory or disinhibited projections to GPe and GPi. Macroscopic quantities are derived which correlate closely to thalamic responses and hence motor programme fidelity. It can be demonstrated that depending on different levels of striatal projections to the GPe and GPi, the dynamics of these macroscopic quantities (synchronisation index, mean synaptic activity and response efficacy) switch from normal to Parkinsonian conditions. Simulating DBS of the STN affects the dynamics of the entire network, increasing the thalamic activity to levels close to normal, while differing from both normal and Parkinsonian dynamics. Using the mentioned macroscopic quantities, the model proposes optimal DBS frequency ranges above 130 Hz.

Multiscale modeling of brain dynamics: from single neurons and networks to mathematical tools.

The extreme complexity of the brain naturally requires mathematical modeling approaches on a large variety of scales; the spectrum ranges from single neuron dynamics over the behavior of groups of neurons to neuronal network activity. Thus, the connection between the microscopic scale (single neuron activity) to macroscopic behavior (emergent behavior of the collective dynamics) and vice versa is a key to understand the brain in its complexity. In this work, we attempt a review of a wide range of approaches, ranging from the modeling of single neuron dynamics to machine learning. The models include biophysical as well as data-driven phenomenological models. The discussed models include Hodgkin-Huxley, FitzHugh-Nagumo, coupled oscillators (Kuramoto oscillators, Rössler oscillators, and the Hindmarsh-Rose neuron), Integrate and Fire, networks of neurons, and neural field equations. In addition to the mathematical models, important mathematical methods in multiscale modeling and reconstruction of the causal connectivity are sketched. The methods include linear and nonlinear tools from statistics, data analysis, and time series analysis up to differential equations, dynamical systems, and bifurcation theory, including Granger causal connectivity analysis, phase synchronization connectivity analysis, principal component analysis (PCA), independent component analysis (ICA), and manifold learning algorithms such as ISOMAP, and diffusion maps and equation-free techniques. WIREs Syst Biol Med 2016, 8:438-458. doi: 10.1002/wsbm.1348 For further resources related to this article, please visit the WIREs website.

Coarse-grained particle model for pedestrian flow using diffusion maps.

Interacting particle systems constitute the dynamic model of choice in a variety of application areas. A prominent example is pedestrian dynamics, where good design of escape routes for large buildings and public areas can improve evacuation in emergency situations, avoiding exit blocking and the ensuing panic. Here we employ diffusion maps to study the coarse-grained dynamics of two pedestrian crowds trying to pass through a door from opposite sides. These macroscopic variables and the associated smooth embeddings lead to a better description and a clearer understanding of the nature of the transition to oscillatory dynamics. We also compare the results to those obtained through intuitively chosen macroscopic variables.

Independent component analysis of high-resolution imaging data identifies distinct functional domains.

In the vertebrate brain external stimuli are often represented in distinct functional domains distributed across the cortical surface. Fast imaging techniques used to measure patterns of population activity record movies with many pixels and many frames, i.e., data sets with high dimensionality. Here we demonstrate that principal component analysis (PCA) followed by spatial independent component analysis (sICA), can be exploited to reduce the dimensionality of data sets recorded in the olfactory bulb and the somatosensory cortex of mice as well as the visual cortex of monkeys, without loosing the stimulus-specific responses. Different neuronal populations are separated based on their stimulus-specific spatiotemporal activation. Both, spatial and temporal response characteristics can be objectively obtained, simultaneously. In the olfactory bulb, groups of glomeruli with different response latencies can be identified. This is shown for recordings of olfactory receptor neuron input measured with a calcium-sensitive axon tracer and for network dynamics measured with the voltage-sensitive dye RH 1838. In the somatosensory cortex, barrels responding to the stimulation of single whiskers can be automatically detected. In the visual cortex orientation columns can be extracted. In all cases artifacts due to movement, heartbeat or respiration were separated from the functional signal by sICA and could be removed from the data set. sICA following PCA is therefore a powerful technique for data compression, unbiased analysis and dissection of imaging data of population activity, collected with high spatial and temporal resolution.

Visualization of individual growth-related craniofacial changes based on cephalometric landmark data: a pilot study.

OBJECTIVE: An approach based on Euclidean distances between cephalometric landmarks is presented (1) to visualize and localize the individual shape changes of the complex craniofacial skeleton during growth and (2) to depict the individual dynamic behavior of developmental size and shape changes. PATIENTS AND METHOD: Growth-related craniofacial changes were investigated exemplarily for two male orthodontically untreated subjects from the Belfast Growth Study on the basis of lateral cephalograms at 7, 9, 11, 13, and 15 years. The interlandmark distances among seven skeletal cephalometric landmarks served as a database for the study. A modified Karhunen-Loève decomposition based on orthogonal modes and time-dependent scalar amplitudes was used to describe the growth process. The individual shape changes of the various craniofacial regions were visualized by allocation of colors to the respective distances, and overdrawn representations were reconstructed by means of multidimensional scaling. RESULTS AND CONCLUSIONS: This visualization technique allows anatomical regions to be characterized with respect to reduced or strengthened growth, compared with pure size changes. The clinically relevant mechanisms of craniofacial changes are visualized (e.g., shifts in the anteroposterior or vertical dimensions of the jaws in relation to cranial base and structural imbalances during development). In addition, overdrawing the effects of shape change on the skeletal structures gives a more readily comprehensible impression of the growth process. Taking account of the methodical limitations of this approach (e.g., the restrictions concerning the number of landmarks), the clinician may take advantage of this technique in orthodontic or surgical diagnostics to gain additional insight into the individual complex size and shape changes during development along with their dynamic behavior.