Info

FIGURE 3.4 Data are queried and extracted from the CoCoDat database using the SearchBoard (accessible from the SwitchBoard by clicking Experimental Data under the Perform Search heading see Figure 3.1). Here, an example illustrates a query for data on IonicConductances from GM-Ctx_Gen (general cortex), GM-L_Gen (general layer), GM-C_Pyr (pyramidal cell), GM-Dend_Ap (apical dendrite). In the expanded hierarchies, numbers in parentheses following the BrainSites indicate the number of returned...

Adding New Kinds Of Mechanisms

NEURON has a special programming language called NMODL that can be used to enlarge its library of biophysical mechanisms (active currents, buffers, diffusion, exchange pumps etc.) (Hines and Carnevale 2000 chapter 9 in Carnevale and Hines, 2006) and also to define new types of synapses and artificial spiking cells that can interact with NEURON's event delivery system (see Modeling networks below). NMODL offers many examples of how NEURON allows modelers to work with familiar concepts and focus...

References

Bergey, G., Britton, J., Cascino, G. et al. (2002). Implementation of an external responsive neurostimulator system (eRNS) in patients with intractable epilepsy undergoing intractable seizure monitoring. Epilepsia (AES abstract). Bragin, A. et al. (1999a). Hippocampal and entorhinal cortex high-frequency oscillations (100-500 Hz) in human epileptic brain and in kainic acid-treated rats with chronic seizures. Epilepsia 40(2) 127-137. Bragin, A. et al. (1999b). High-frequency oscillations in...

Thalamocortical Mechanisms For Absence Seizures

As reviewed above, thalamic circuits can generate hypersynchronized oscillations at 3 Hz, resembling the typical oscillation frequency during absence seizures. However, there is ample evidence that the thalamus is not sufficient to explain seizure generation. GABAa-receptor antagonists induce spike-and-wave seizures when applied to cerebral cortex Gloor et al., 1977 Fisher and Prince, 1977a Steriade and Contreras, 1998 , while they fail to generate such paroxysms when injected to the thalamus...

Fp1

FIGURE 13.1 Electroencephalogram EEG recording during an absence seizure in a human subject. A Absence seizure in different EEG leads FP1 and FP2 measure the potential difference between frontal and parietal regions of the scalp, whereas O1 and O2 correspond to the measures between occipital regions . The seizure lasted approximately five seconds and consisted of an oscillation at around 3 Hz which appeared nearly-simultaneously in all EEG leads. B Same seizure at higher temporal resolution,...

Tra

Electrodecremental

FIGURE 28.2 Intracranial recordings of selective subdural grid contacts of a complex partial seizure from several electrodes close to the epileptic focus. LBT57-LBT58 is the electrode pair the closest to the focus. The different phases of the seizure are marked and detailed in Figure 28.3. FIGURE 28.2 Intracranial recordings of selective subdural grid contacts of a complex partial seizure from several electrodes close to the epileptic focus. LBT57-LBT58 is the electrode pair the closest to the...

Intrinsic Potential Connectivity Patterns

Dendritic Morphology Ca1 Hippocampus

Electron microscopy showed that synaptic specialization may exist without a physical contact between an axon and a dendrite Palay, 1958 Gray, 1959a, 1959b . Experiments have demonstrated the plastic nature of spines in establishing and remodeling a synaptic contact with the presynaptic machinery Lendvai et al., 2000 Matsuzaki et al., 2004 . In this context, a potential synapse can be defined as the condition of an axonal segment passing within a specified distance depending on the type of...

An Outline For Building Network Models

A network model in NEURON can involve any combination of artificial spiking cells and mechanistic model cells. We already know that biophysical model cells are constructed from sections and density mechanisms. We also know that an event-triggered synapse onto a biophysical model cell is a point process attached to a section, which is capable of responding to an input event by affecting membrane current, concentration of a second messenger, or some other variable at the point of attachment....

Fabrication

Mea Fabrication

Our MEAs are constructed in conjunction with Thin Films Technology, Inc. Buellton, CA . The multisite MEAs are mass fabricated using photolithographic methods, as this technique routinely produces recording surfaces microns in size, greatly improving the spatial resolution as compared to microdialysis. Details of the fabrication process are outlined in Burmeister et al. 2001 . Briefly, photolithography helps decrease overall production costs as multiple MEAs can be fabricated with minimal...

Generalities On Gap Junction Mediatedcoupling In Gabaergic Networks Of The Hippocampus

Not too many years ago, neuroscience textbooks reported that gap junctions are relatively rare between adult mammalian neurons. This view has now radically changed. Great advances in the study of electrical coupling in cortical networks have come as the result of technical developments allowing the simultaneous recording from multiple neurons in 'in vitro' slices Miles and Poncer, 1996 . These experimental arrangements provide an excellent model to study the connectivity of specific brain...

Triangulation Algorithm And Surface Representation

Hippocampus Rat Brain

Each individual pixel-based closed polygon representing a cyto-architectonic layer boundary in a given section was 'triangulated' to identify or 'fill' all pixels inside the contour, representing an inner position of the respective anatomical subregion. The novel algorithm, written in C and illustrated in Figure 6.2, uses circular linked lists Kernighan and Ritchie, 1998 and is applicable to both convex and concave polygons. This procedure is analogous to the Marching Cube approach Lorensen and...

Microelectrodebased Epilepsy Therapy Coupled With Neural Prostheses For Maintenance Of Hippocampal Function

Hippocampal Prosthesis Image

Outside basic science investigation, the clinical applications of our MEA technology are equally promising in their novelty and diversity. Based upon acute basal recordings during seizure focus resection surgery, discrete brain regions could conceivably be 'mapped' to isolate diseased from non-diseased tissue. With alternative modeling and prediction algorithm developments, chronic MEA technology could be coupled to local drug delivery, therefore circumventing adverse side-effects of systemic...

Volumetric Analysis

The computational framework described above decomposes the 3D volume of the hippocampus into 4096 m3 16 m 16 m 16 m voxels. The centers of the voxels within the granule and pyramidal cell layers are assigned to correspond to a soma location, approximating the tight neuronal packing of principal cells in the real tissue Claiborne et al., 1990 Ishizuka et al., 1995 . The resulting number of soma positions in the granule cell layer covering the whole septo-temporal extent was 0.9x 106. For...

Experimental Characterization And Mathematical Modeling Of The Nonlinear Dynamic Properties Of The Hippocampal Ca3

Our strategy for achieving a hippocampal neural prosthesis is based on several system requirements for replacing any CNS region with a biomimetic device that interacts bi-directionally with the rest of the undamaged brain i.e. sensing and communicating input to the biomimetic device from afferents of the damaged region communicating and electrically stimulating outputs from the biomimetic device to efferents of the damaged region Berger et al., 2001 . First and foremost is the nature of the...

Cadd And Modeling Anticonvulsant Drugs

Tricyclic Butterfly

Modern CADD calculations particularly quantum mechanics calculations are being used to study smaller molecules such as anticonvulsant drugs Weaver, 1996 Carter et al., 2003 . Unlike the molecular mechanics calculations on large receptor proteins, these drug molecule calculations are highly accurate, rivalling high quality experimental studies. This accuracy is exemplified by a recent study of tricyclic anticonvulsant drugs. Tricyclic molecules are frequently used to treat a diversity of...

Ass A1 As9 A1 A40 A1 A41 A1 A42 A1 A4s A1 A44 A1 A4s A1 A4s A1 A47 A1 A4s A1 A49 A1 As0 A1 As1 A1 As2 A1 Ass A1

Figure 27.4 A two-minute segment of a seizure outlined by a black horizontal bar at the top, with DC shift that slowly increases as the seizure progresses. Modified with permission from Ikeda et al., 1996. figure 27.4 A two-minute segment of a seizure outlined by a black horizontal bar at the top, with DC shift that slowly increases as the seizure progresses. Modified with permission from Ikeda et al., 1996. accompanied by a suppression of amplitude of other EEG patterns Figure 27.4 . This...

Contributors

Ascoli Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA Susan E. Bachus Krasnow Institute for Advanced Study, George Mason University, Fairfax, VA Ernest Barreto Krasnow Institute for Advanced Study, Department of Physics and Astronomy, George Mason Universit, Fairfax, VA Maxim Bazhenov The Salk Institute for Biological Studies, La Jolla, CA Meriem K. Bensalem-Owen Department of Neurology, University of Kentucky College of Medicine, Lexington, KY Theodore...

Application Practicalities

Neuroconstruct

The application is freely available and details can be found at http www.neuroConstruct.org. It is a desktop based application written in Java, and so can be run on a wide range of machine architectures and operating systems. Automatic installers are available for Windows, Mac OS and Linux. The main interface is shown in Figure 5.1A. The network models are organized into projects containing all of the constituent elements cell types, 3D region information, network connections, etc. . While...

Extracting And Visualizing Datasets

To extract datasets from the MS Access version of CoCoDat, the user opens the SearchBoard from the main SwitchBoard see Figure 3.1 by clicking Experimental Data under the heading Perform Search. To form a query, the user selects the desired combination of BrainRegion, Layer, NeuronType, NeuronCompartment and DataType Morphology, FiringProp-erties, IonicConductances, IonicCurrents, SynapticCurrents or Connectivity with the optional specification of Species. The selected search terms are combined...

Feature Extraction

The inputs to decision support systems are features - quantitative or qualitative measures that distill raw data into relevant information for tasks such as classification, regression, density estimation and clustering. This is the least understood and most difficult part of the pattern recognition problem Glorioso, 1975 . Features can be univariate versus multivariate e.g. single versus multiple channels of data fed in , scalar-valued versus vector-valued, single-natured versus multinatured...

Cell Types To Include

Next, let us consider the major players in the above changes. The granule cells are the primary output cells and are both the source and major target of sprouting and, for sure, form an essential part of the model. Mossy cells, the second most numerous cell type in the dentate also possess the widest axonal span and maximum number of connections see Tables 7.1, 7.2 and Figure 7.1B . Loss of this excitatory cell type is likely to influence directly the excitability of the network Ratzliff et...

The Role Of Microelectrodes In Epilepsy Therapy And Hippocampal Repair

In parallel with use of the enzyme-based MEA to monitor characteristic seizure-associated chemical neuronal communication, we also are currently exploring potential uses of combined MEA-computational modeling techniques for development of hippocampal prosthetics, incorporating unit recordings and electrical stimulation in specific conformal Pt site arrangements to assist information relay through an inhibited, or even damaged, trisynaptic circuit. Actual development of this FIGURE 33.7...

Excitatory And Inhibitory Interplay In Seizure Patterns

Olm Interneuron

There are a number of studies of in vitro intracellular excitatory-inhibitory EI interplay. These works focused primarily on stimulation-induced epileptiform activity Perez-Velazquez and Carlen, 1999 Perez-Velazquez, 2003 Fujiwara-Tsukamoto et al., 2004 . In these paradigms, tetanic stimulation replaced pre-ictal and ictal onset dynamics and the resulting after-discharges demonstrated synchronous activation of inhibitory and excitatory cells Fujiwara-Tsukamoto et al., 2004 . However, we know...

Matching Pursuit And Gad Methods

Matching pursuit MP is an analysis based on the decomposition of a signal into simpler and smaller signal elements called atoms. The method was introduced by Mallat and Zhang in 1993 Mallat and Zhang, 1993 . Although various atoms can be used, the most common ones are based on the Gabor function, which is a Gaussian modulated oscillation. The MP method can be applied to any signal and has no requirements for stationarity of the signal. The MP pursuit algorithm is a significant improvement in...

Effect Of Intrinsic And Synaptic Currents And Spontaneous Activity

Increasing gKca or the parameter U of short-term synaptic depression decreased burst duration and the number of spikes per burst Figure 17.7A, left and middle-left . A complete block of Z ca amp KCa 0 or short-term synaptic depression U 0 caused burst discharges to sustain indefinitely. NMDA current at PY-PY synapses modulated burst duration and number of spikes in a similar manner Figure 17.7A, middle-right . Interestingly, blocking NMDA current approximately halved

Materials And Methods Model Structure

The Structure Pyramidal Cells

The model of thalamocortical network is an extended version of the lumped model initially proposed by Lopes da Silva et al. 1974 . Lumped model means that we do not simulate single cells in a distributed network but rather we take a spatial average over a population and deal only with temporal dynamics of the mean values of the underlying statistical process. The model of Lopes da Silva was based on two interacting populations of neurons, namely excitatory cells of main population that...

With The Ca3 Prosthesis

Recall that the goal of this multidisciplinary effort is to achieve the stage 1 prosthetic system for the hippocampal slice by integrating the components described above. More specifically, we seek functionally to replace the biological CA3 subregion of the hippocampal slice with an FPGA VLSI-based model of the non-linear dynamics of CA3, such that the figure 33.16 System integration of an FPGA-based non-linear model of the CA3 hippocampal region with a hippocampal slice in which the output...

Cortical Origin Of Paroxysmal Oscillations Generated Within The Thalamocortical System

Pyramidal Cells

The origin of seizures that accompany various types of epileptic activities is unclear. Here we focus on neocortical seizures. The etiologies of epilepsies with cortical seizures include cortical dysplasia, traumatic injury and other idiopathic causes Stafstrom, 2005 . Anesthetized or naturally sleeping and awake cats exhibit seizures with transitions between periods of spike-wave complexes 2-3 Hz and fast runs 10-15 Hz Steriade and Contreras, 1995 Steriade et al., 1998 Timofeev and Steriade,...

Hierarchical Cluster Organization Of Neural Systems

It is known from the anatomy of the brain that cortical architecture and connections are organized in a hierarchical and modular way, from cellular microcircuits in cortical columns Binzegger et al., 2004 at the lowest level, via cortical areas at the intermediate level, to clusters of highly connected brain regions at the global systems level Hilgetag et al., 2000 Hilgetag and Kaiser, 2004 Sporns et al., 2004 . At each level clusters arise, with denser connectivity within than between the...

Cortical Versus Thalamocortical Seizures

The models investigated here displayed oscillations with spike-and-wave field potentials arising either from intracortical mechanisms or from thalamocortical loops. As outlined above, the two types of seizures display fundamental differences. First, the oscillation frequency is slower in intracortical seizures compared to thalamocortical seizures 1.8-2.5 Hz compared to 2-4 Hz Steriade and Contreras, 1998 Figure 13.19 . The same was observed in the models 1.3 Hz in Figure 13.10 compared to 2-4...

Potential Mechanisms Of Seizure Associated Slow Waves

It is not clear at this moment whether slow waves that occur only at the seizure onset and those that gradually appear during seizure development or at seizure termination are generated by the same or different mechanisms. To the best of our knowledge there are no publications that have studied mechanisms of generation of these waves in the same experimental environment. The majority of existing publications are dedicated to the analysis of mechanism of DC shift during development of acutely...

Accessing The Cocodat Database

The CoCoDat database can be freely downloaded as a Microsoft Access 2000 database mdb file from http www.cocomac.org cocodat along with a manual detailing the procedures for entering, querying and extracting datasets. CoCoDat is copy-lefted under the GNU General Public License http www.gnu.org licenses gpl.html . By opening the database, the user is automatically taken to the central CoCoDat SwitchBoard see Figure 3.1 that gives access to all forms for entering and retrieving data....

Ropireddy Deepak

Rise of the Machines - On the Threshold of a new Era in Epilepsy Research Daniel H. Lowenstein Introduction Applications and Emerging concepts of computational neuroscience in Epilepsy Research xv Computational Modeling Techniques and Databases 1 Simulation of Large Networks Technique and Progress 3 William W. Lytton, Mark Stewart and Michael Hines 2 The NEURON Simulation Environment in Epilepsy Research 18 3 The CoCoDat Database Systematically Organizing and Selecting Quantitative Data on...

Thalamocortical Loop Mechanism For Absence Seizures

The mechanism proposed for absence seizures can be summarized as follows. During sleep spindles, the oscillation is generated by intrathalamic interactions TC-RE loops and is reinforced by thalamocortical loops, as suggested in a previous model Destexhe et al., 1998a . The combined action of intrathalamic and thalamocortical loops provides RE cells with moderate excitation, which evokes GABAA-mediated IPSPs in TC cells and sets the frequency to 10Hz. During spike-and-wave seizures, due to...