Ion dynamics at the energy-deprived tripartite synapse.

The anatomical and functional organization of neurons and astrocytes at 'tripartite synapses' is essential for reliable neurotransmission, which critically depends on ATP. In low energy conditions, synaptic transmission fails, accompanied by a breakdown of ion gradients, changes in membrane potentials and cell swelling. The resulting cellular damage and cell death are causal to the often devastating consequences of an ischemic stroke.

Neural field models with transmission delays and diffusion.

A neural field models the large scale behaviour of large groups of neurons. We extend previous results for these models by including a diffusion term into the neural field, which models direct, electrical connections. We extend known and prove new sun-star calculus results for delay equations to be able to include diffusion and explicitly characterise the essential spectrum.

Pathological responses to single-pulse electrical stimuli in epilepsy: The role of feedforward inhibition.

Delineation of epileptogenic cortex in focal epilepsy patients may profit from single-pulse electrical stimulation during intracranial EEG recordings. Single-pulse electrical stimulation evokes early and delayed responses. Early responses represent connectivity.

A Comparison of Evoked and Non-evoked Functional Networks.

The growing interest in brain networks to study the brain's function in cognition and diseases has produced an increase in methods to extract these networks. Typically, each method yields a different network. Therefore, one may ask what the resulting networks represent.

A framework for directional and higher-order reconstruction in photoacoustic tomography.

Photoacoustic tomography is a hybrid imaging technique that combines high optical tissue contrast with high ultrasound resolution. Direct reconstruction methods such as filtered back-projection, time reversal and least squares suffer from curved line artefacts and blurring, especially in the case of limited angles or strong noise. In recent years, there has been great interest in regularised iterative methods.

A Rate-Reduced Neuron Model for Complex Spiking Behavior.

We present a simple rate-reduced neuron model that captures a wide range of complex, biologically plausible, and physiologically relevant spiking behavior. This includes spike-frequency adaptation, postinhibitory rebound, phasic spiking and accommodation, first-spike latency, and inhibition-induced spiking. Furthermore, the model can mimic different neuronal filter properties.

Quantifying HER-2 expression on circulating tumor cells by ACCEPT.

Circulating tumor cells (CTCs) isolated from blood can be probed for the expression of treatment targets. Immunofluorescence is often used for both the enumeration of CTC and the determination of protein expression levels related to treatment targets. Accurate and reproducible assessment of such treatment target expression levels is essential for their use in the clinic.

Cross-scale effects of neural interactions during human neocortical seizure activity.

Small-scale neuronal networks may impose widespread effects on large network dynamics. To unravel this relationship, we analyzed eight multiscale recordings of spontaneous seizures from four patients with epilepsy. During seizures, multiunit spike activity organizes into a submillimeter-sized wavefront, and this activity correlates significantly with low-frequency rhythms from electrocorticographic recordings across a 10-cm-sized neocortical network.

Phenomenological network models: Lessons for epilepsy surgery.

The current opinion in epilepsy surgery is that successful surgery is about removing pathological cortex in the anatomic sense. This contrasts with recent developments in epilepsy research, where epilepsy is seen as a network disease. Computational models offer a framework to investigate the influence of networks, as well as local tissue properties, and to explore alternative resection strategies.

Estimation and Identifiability of Model Parameters in Human Nociceptive Processing Using Yes-No Detection Responses to Electrocutaneous Stimulation.

Healthy or pathological states of nociceptive subsystems determine different stimulus-response relations measured from quantitative sensory testing. In turn, stimulus-response measurements may be used to assess these states. In a recently developed computational model, six model parameters characterize activation of nerve endings and spinal neurons.

A Biophysical Model for Cytotoxic Cell Swelling.

Unlabelled: We present a dynamic biophysical model to explain neuronal swelling underlying cytotoxic edema in conditions of low energy supply, as observed in cerebral ischemia. Our model contains Hodgkin-Huxley-type ion currents, a recently discovered voltage-gated chloride flux through the ion exchanger SLC26A11, active KCC2-mediated chloride extrusion, and ATP-dependent pumps. The model predicts changes in ion gradients and cell swelling during ischemia of various severity or channel blockage with realistic timescales.

Sparse pallidal connections shape synchrony in a network model of the basal ganglia.

Neural synchrony in the basal ganglia, especially in the beta frequency band (13-30 Hz), is a hallmark of Parkinson's disease and considered as antikinetic. In contrast, the healthy basal ganglia show low levels of synchrony. It is currently unknown where synchrony and oscillations arise in the parkinsonian brain and how they are transmitted through the basal ganglia, as well as what makes them dependent on dopamine.

Dependence of Nociceptive Detection Thresholds on Physiological Parameters and Capsaicin-Induced Neuroplasticity: A Computational Study.

Physiological properties of peripheral and central nociceptive subsystems can be altered over time due to medical interventions. The effective change for the whole nociceptive system can be reflected in changes of psychophysical characteristics, e.g.

Computational modeling of Adelta-fiber-mediated nociceptive detection of electrocutaneous stimulation.

Sensitization is an example of malfunctioning of the nociceptive pathway in either the peripheral or central nervous system. Using quantitative sensory testing, one can only infer sensitization, but not determine the defective subsystem. The states of the subsystems may be characterized using computational modeling together with experimental data.

Modeling focal epileptic activity in the Wilson-cowan model with depolarization block.

Unlabelled: Measurements of neuronal signals during human seizure activity and evoked epileptic activity in experimental models suggest that, in these pathological states, the individual nerve cells experience an activity driven depolarization block, i.e. they saturate.

Exploiting pallidal plasticity for stimulation in Parkinson's disease.

Objective: Continuous application of high-frequency deep brain stimulation (DBS) often effectively reduces motor symptoms of Parkinson's disease patients. While there is a growing need for more effective and less traumatic stimulation, the exact mechanism of DBS is still unknown. Here, we present a methodology to exploit the plasticity of GABAergic synapses inside the external globus pallidus (GPe) for the optimization of DBS.

Pallidal gap junctions-triggers of synchrony in Parkinson's disease?

Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively).

Phase-locking of epileptic spikes to ongoing delta oscillations in non-convulsive status epilepticus.

The EEG of patients in non-convulsive status epilepticus (NCSE) often displays delta oscillations or generalized spike-wave discharges. In some patients, these delta oscillations coexist with intermittent epileptic spikes. In this study we verify the prediction of a computational model of the thalamo-cortical system that these spikes are phase-locked to the delta oscillations.

Synchrony in Parkinson's disease: importance of intrinsic properties of the external globus pallidus.

The mechanisms for the emergence and transmission of synchronized oscillations in Parkinson's disease, which are potentially causal to motor deficits, remain debated. Aside from the motor cortex and the subthalamic nucleus, the external globus pallidus (GPe) has been shown to be essential for the maintenance of these oscillations and plays a major role in sculpting neural network activity in the basal ganglia (BG). While neural activity of the healthy GPe shows almost no correlations between pairs of neurons, prominent synchronization in the β frequency band arises after dopamine depletion.

Analysis of stability and bifurcations of fixed points and periodic solutions of a lumped model of neocortex with two delays.

A lumped model of neural activity in neocortex is studied to identify regions of multi-stability of both steady states and periodic solutions. Presence of both steady states and periodic solutions is considered to correspond with epileptogenesis. The model, which consists of two delay differential equations with two fixed time lags is mainly studied for its dependency on varying connection strength between populations.

Efficacy, nephrotoxicity and ototoxicity of aminoglycosides, mathematically modelled for modelling-supported therapeutic drug monitoring.

Therapeutic drug monitoring (TDM) of aminoglycosides has been a topic during the last thirty years. There is a tendency that - because of the once-daily regimen - TDM is considered not necessary anymore. Although once daily dosing has the potential for decreased toxicity, long-term usage can cause severe nephro- and ototoxicity.

Comparing epileptiform behavior of mesoscale detailed models and population models of neocortex.

Two models of the neocortex are developed to study normal and pathologic neuronal activity. One model contains a detailed description of a neocortical microcolumn represented by 656 neurons, including superficial and deep pyramidal cells, four types of inhibitory neurons, and realistic synaptic contacts. Simulations show that neurons of a given type exhibit similar, synchronized behavior in this detailed model.

Frequency-selectivity of a thalamocortical relay neuron during Parkinson's disease and deep brain stimulation: a computational study.

In this computational study, we investigated (i) the functional importance of correlated basal ganglia (BG) activity associated with Parkinson's disease (PD) motor symptoms by analysing the effects of globus pallidus internum (GPi) bursting frequency and synchrony on a thalamocortical (TC) relay neuron, which received GABAergic projections from this nucleus; (ii) the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on the response of the TC relay neuron to synchronized GPi oscillations; and (iii) the functional basis of the inverse relationship that has been reported between DBS frequency and stimulus amplitude, required to alleviate PD motor symptoms [A. L. Benabid et al.