Modeling pathological brain rhythms: constructing a neural mass model from single cell dynamics

Neural mass models (NMM) describe neural activity on a macroscopic scale, which can be compared to the electroencephalogram (EEG). This allows a better understanding of the processes responsible for various EEG patterns, including pathological rhythms as diffuse slowing or burst-suppression [1]. Using available models which contain explicit expressions for the synaptic response and number of synapses [2], pathological conditions that modulate synaptic function, such as anesthetics [3] and hypoxia, can be included easily. However, it is less obvious how to incorporate conditions which alter the excitability of neurons, such as hyperkalemia or channel blockers. Here, we present a method for constructing a neural mass model by using the relation between synaptic input of a single cell model and its firing rate. This allows an easy implementation for pathological conditions. We describe the average firing rate of a single population of neurons receiving one type of synaptic input, but this can readily be extended to multiple populations. A set of differential equations describes, traditionally, the average synaptic conductance [2]. Assuming Poisson statistics for the input, we can derive another equation, which describes the time evolution of the standard deviation of the synaptic conductance across the population. The average and standard deviation of the conductance then determine the distribution and the corresponding average of the firing rates in the population. As initial verification, the constructed mean field model is numerically compared to a network of single cells. From the single cell model we determine the dependence of the firing rate on (constant) synaptic conductance numerically. Furthermore, we show that, for fluctuating inputs, the firing rate is well approximated by the instantaneous synaptic conductance. 120 Hodgkin-Huxley type cells were connected all-to-all with inhibitory synapses: a simple configuration which results in intrinsic oscillations. Each cell receives inhibitory external input as well, consisting of Poisson trains. We find a close agreement between the constructed neural mass model and the network simulation (Figure 1). Figure 1. Comparison of step response of the derived NMM and a detailed network model The proposed method can easily be extended to model heterogeneous populations, multiple types of synapses, spatial structures, propagation delays, and bursting dynamics [4]. Any pathophysiology can readily be incorporated by adapting the single cell model. This allows for testing hypotheses on processes underlying abnormal EEGs

An objective approach for Burkholderia pseudomallei strain selection as challenge material for medical countermeasures efficacy testing

Burkholderia pseudomallei is the causative agent of melioidosis, a rare disease of biodefense concern with high mortality and extreme difficulty in treatment. No human vaccines are available that protect against B. pseudomallei infection, and with the current limitations of antibiotic treatment, the development of new preventative and therapeutic interventions is crucial. Although clinical trials could be used to test the efficacy of new medical countermeasures (MCMs), the high mortality rates associated with melioidosis raises significant ethical issues concerning treating individuals with new compounds with unknown efficacies. The US Food and Drug Administration (FDA) has formulated a set of guidelines for the licensure of new MCMs to treat diseases in which it would be unethical to test the efficacy of these drugs in humans. The FDA “Animal Rule” 21 CFR 314 calls for consistent, well-characterized B. pseudomallei strains to be used as challenge material in animal models. In order to facilitate the efficacy testing of new MCMs for melioidosis using animal models, we intend to develop a well-characterized panel of strains for use. This panel will comprise of strains that were isolated from human cases, have a low passage history, are virulent in animal models, and are well-characterized phenotypically and genotypically. We have reviewed published and unpublished data on various B. pseudomallei strains to establish an objective method for selecting the strains to be included in the panel of B. pseudomallei strains with attention to five categories: animal infection models, genetic characterization, clinical and passage history, and availability of the strain to the research community. We identified 109 strains with data in at least one of the five categories, scored each strain based on the gathered data and identified six strains as candidate for a B. pseudomallei strain panel

Decision noise may mask criterion shifts: Reply to Balakrishnan and MacDonald (2008)

J. D. Balakrishnan and J. A. MacDonald (2008) argue that RTbased measures of signal detection processes provide evidence against signal detection theory’s notion of a flexible decision criterion. They argue that this evidence is immune to the alternative explanation proposed by S. T. Mueller and C. T. Weidemann (2008), that decision noise may mask criterion shifts. We show that noise in response times can produce the same effects as are produced by noise in confidence ratings. Given these results, the evidence is not sufficient to categorically reject the notion of a flexible response policy implemented through shifts in a decision criterion

La Grange, Texas Housing Needs Assessment

A housing quality study was conducted to evaluate the current housing stock in the City of La Grange. It was found that the majority of housing is maintained or well maintained and that although the City has an older housing stock, it is very well taken care of. There has been no new residential construction since 2010 and the vacancy rate for owner occupied households is at zero percent. Housing tenure patterns show that many residents moved into their homes during the period of 2000 to 2009 and growth has continued since then. Housing is affordable within the City, especially for owner occupied households. The City is however, lacking in housing options for renters and the elderly.The City of La Grange has been experiencing growth at a higher rate than expected in the City’s comprehensive plan. Due to this, the City is nearing build out capacity and housing has become limited. Local real estate agents and developers have expressed concern to the City in regards to the limited housing options for their clients. In response, the City contacted Texas Target Communities at Texas A&M University to conduct a Housing Needs Assessment. The purpose of this assessment is to provide an inventory of current housing, identify future demand, and explore other possible housing related issues and, or concerns for the area.Texas Target Communitie

Acoustic Spectroscopy of the DNA in GHz range

We find a parametric resonance in the GHz range of the DNA dynamics, generated by pumping hypersound . There are localized phonon modes caused by the random structure of elastic modulii due to the sequence of base pairs

Long-Term Seizure Suppression and Optogenetic Analyses of Synaptic Connectivity in Epileptic Mice with Hippocampal Grafts of GABAergic Interneurons

Studies in rodent epilepsy models suggest that GABAergic interneuron progenitor grafts can reduce hyperexcitability and seizures in temporal lobe epilepsy (TLE). Although integration of the transplanted cells has been proposed as the underlying mechanism for these disease-modifying effects, prior studies have not explicitly examined cell types and synaptic mechanisms for long-term seizure suppression. To address this gap, we transplanted medial ganglionic eminence (MGE) cells from embryonic day 13.5 VGAT-Venus or VGAT-ChR2-EYFP transgenic embryos into the dentate gyrus (DG) of adult mice 2 weeks after induction of TLE with pilocarpine. Beginning 3–4 weeks after status epilepticus, we conducted continuous video-electroencephalographic recording until 90–100 d. TLE mice with bilateral MGE cell grafts in the DG had significantly fewer and milder electrographic seizures, compared with TLE controls. Immunohistochemical studies showed that the transplants contained multiple neuropeptide or calcium-binding protein-expressing interneuron types and these cells established dense terminal arborizations onto the somas, apical dendrites, and axon initial segments of dentate granule cells (GCs). A majority of the synaptic terminals formed by the transplanted cells were apposed to large postsynaptic clusters of gephyrin, indicative of mature inhibitory synaptic complexes. Functionality of these new inhibitory synapses was demonstrated by optogenetically activating VGAT-ChR2-EYFP-expressing transplanted neurons, which generated robust hyperpolarizations in GCs. These findings suggest that fetal GABAergic interneuron grafts may suppress pharmacoresistant seizures by enhancing synaptic inhibition in DG neural circuits

Is it really search or just matching? The influence of goodness, number of stimuli and presentation sequence in same-different tasks

The Goodness of Garner dot patterns has been shown to influence same-different response times in a specific way, which has led to the formulation of a memory search model of pattern comparison. In this model, the space of possible variations of each pattern is searched separately for each pattern in the comparison, resulting in faster response times for patterns that have fewer alternatives. Compared to an alternative explanation based on stimulus encoding plus mental rotation, however, the existing data strongly favor this explanation. To obtain a more constraining set of data to distinguish between the two possible accounts, we extended the original paradigm to a situation in which participants needed to compare three, rather than two patterns and varied the way the stimuli were presented (simultaneously or sequentially). Our findings suggest that neither the memory search nor the encoding plus mental rotation model provides a complete description of the data, and that the effects of Goodness must be understood in a combination of both mechanisms, or in terms of cascades processing

On the nonlinear dynamics of topological solitons in DNA

Dynamics of topological solitons describing open states in the DNA double helix are studied in the frameworks of the model which takes into account asymmetry of the helix. It is shown that three types of topological solitons can occur in the DNA double chain. Interaction between the solitons, their interactions with the chain inhomogeneities and stability of the solitons with respect to thermal oscillations are investigated.Comment: 16 pages, 16 figure