Saurabh R. Sinha

Determination of current density distributions generated by electrical stimulation of the human cerebral cortex

With the use of a 3-dimensional finite element model of the human brain based on structural data from MRI scans, we simulated patterns of current flow in the cerebral hemisphere with different types of electrical stimulation. Five different tissue types were incorporated into the model based on conductivities taken from the literature. The boundary value problem derived from Laplaces equation was solved with a quasi-static approximation. Transcranial electrical stimulation with scalp electrodes was poorly focussed and required high levels of current for stimulation of the cortex. Direct cortical stimulation with bipolar (adjacent) electrodes was found to be very effective in producing localized current flows. Unipolar cortical stimulation (with a more distant reference electrode) produced higher current densities at the same stimulating current as did bipolar stimulation, but stimulated a larger region of the cortex. With the simulated electrodes resting on the pia-arachnoid, as usually occurs clinically, there was significant shunting of the current (7/8 of the total current) through the CSF. Possible changes in electrodes and stimulation parameters that might improve stimulation procedures are considered.

A Prospective Study of the Modified Atkins Diet for Intractable Epilepsy in Adults

Purpose: The ketogenic diet is not typically offered to adults with epilepsy due to the significant lifestyle alterations needed for its use. The modified Atkins diet has been recently demonstrated to be therapeutic for children without the need for an admission, fasting period, weighing of foods, or fluid, calorie, and protein restriction.

Astrocyte Glutamate Transporters Regulate Metabotropic Glutamate Receptor-Mediated Excitation of Hippocampal Interneurons

Clearance of extracellular glutamate is essential for limiting the activity of metabotropic glutamate receptors (mGluRs) at excitatory synapses; however, the relative contribution of transporters found in neuronal and glial membranes to this uptake is poorly understood. Hippocampal interneurons located at the oriens-alveus border express mGluR1α, a metabotropic glutamate receptor that regulates excitability and synaptic plasticity. To determine which glutamate transporters are essential for removing glutamate at these excitatory synapses, we recorded mGluR1-mediated EPSCs from oriens-lacunosum moleculare (O-LM) interneurons in acute hippocampal slices. Stimulation in stratum oriens reliably elicited a slow mGluR1-mediated current in O-LM interneurons if they were briefly depolarized to allow Ca2+ entry before stimulation. Selective inhibition of GLT-1 [for glutamate transporter; EAAT2 (for excitatory amino acid transporter)] with dihydrokainate increased the amplitude of these responses approximately threefold, indicating that these transporters compete with mGluRs for synaptically released glutamate. However, inhibition of all glutamate transporters with TBOA (dl-threo-b-benzyloxyaspartic acid) increased mGluR1 EPSCs >15-fold, indicating that additional transporters also shape activation of these receptors. To identify these transporters, we examined mGluR1 EPSCs in mice lacking GLAST (for glutamate-aspartate transporter; EAAT1) or EAAC1 (for excitatory amino acid carrier; EAAT3). A comparison of responses recorded from wild-type and transporter knock-out mice revealed that the astroglial glutamate transporters GLT-1 and GLAST, but not the neuronal transporter EAAC1, restrict activation of mGluRs in O-LM interneurons. Transporter-dependent potentiation of mGluR1 EPSCs led to a dramatic increase in interneuron firing and enhanced inhibition of CA1 pyramidal neurons, suggesting that acute or prolonged disruption of transporter activity could lead to changes in network activity as a result of enhanced interneuron excitability.

Presynaptic calcium dynamics and transmitter release evoked by single action potentials at mammalian central synapses

The relationship between presynaptic calcium transients ([Ca2+]t) and transmitter release evoked by a single stimulus was both investigated experimentally and modeled at a mammalian central synapse, the CA3 to CA1 pyramidal cell synapse in guinea pig hippocampal slices. In the present study, we compared the low-affinity calcium indicator furaptra with the higher-affinity indicator fura-2. The 10-90% rise time of the furaptra transient was 2.4 ms compared to 7.8 ms with fura-2; the half-decay time (tau 1/2) was 30 ms for furaptra, compared to 238 ms for fura-2. The half-width of the calcium influx was 1.8 ms with furaptra, which provides an upper limit to the duration of the calcium current (ICa) evoked by an action potential. Modeling the decay time course of the furaptra transients led to the conclusion that the predominant endogenous calcium buffer in these terminals must have relatively slow kinetics (kon < 10(5)/M.s), although the presence of small amounts of fast buffers cannot be excluded. The relationship between the [Ca2+]t measured with furaptra and the postsynaptic response was the same as previously observed with fura-2: the postsynaptic response was proportional to about the fourth power (m approximately 4) of the amplitude of either [Ca2+]t or calcium influx. Thus, although fura-2 may be locally saturated by the high local [Ca2+] responsible for transmitter release, the volume-averaged fura-2 signal accurately reflects changes in this local concentration. The result that both indicators gave similar values for the power m constrains the amplitude of calcium influx in our model: Ica < 1 pA for 1 ms.

Standardized database development for EEG epileptiform transient detection: EEGnet scoring system and machine learning analysis

The routine scalp electroencephalogram (rsEEG) is the most common clinical neurophysiology procedure. The most important role of rsEEG is to detect evidence of epilepsy, in the form of epileptiform transients (ETs), also known as spike or sharp wave discharges. Due to the wide variety of morphologies of ETs and their similarity to artifacts and waves that are part of the normal background activity, the task of ET detection is difficult and mistakes are frequently made. The development of reliable computerized detection of ETs in the EEG could assist physicians in interpreting rsEEGs. We report progress in developing a standardized database for testing and training ET detection algorithms. We describe a new version of our EEGnet software system for collecting expert opinion on EEG datasets, a completely web-browser based system. We report results of EEG scoring from a group of 11 board-certified academic clinical neurophysiologists who annotated 30-s excepts from rsEEG recordings from 100 different patients. The scorers had moderate inter-scorer reliability and low to moderate intra-scorer reliability. In order to measure the optimal size of this standardized rsEEG database, we used machine learning models to classify paroxysmal EEG activity in our database into ET and non-ET classes. Based on our results, it appears that our database will need to be larger than its current size. Also, our non-parametric classifier, an artificial neural network, performed better than our parametric Bayesian classifier. Of our feature sets, the wavelet feature set proved most useful for classification.

Simultaneous optical recording of evoked and spontaneous transients of membrane potential and intracellular calcium concentration with high spatio-temporal resolution

We have developed a system for simultaneous optical recording of transients of membrane potential and intracellular calcium concentration from mammalian brain slice preparations with high spatio-temporal resolution. Simultaneous recording was achieved by using two dedicated photodetectors together with two fluorescent indicators. Specifically, the calcium-sensitive dye Calcium Orange and the voltage-sensitive dye RH-414 were selected because they have overlapping excitation spectra, but separable emission spectra. Transverse guinea pig hippocampal slices were double-loaded by bath application of the membrane-permeant form of Calcium Orange and RH-414. Transients of intracellular calcium concentration and membrane potential associated with evoked neural activity in hippocampal areas CA1 and CA3 were recorded. Furthermore, we have recorded calcium and voltage transients associated with spontaneous epileptiform activity induced by bath application of an epileptogenic drug, 4-aminopyridine. The use of photodiode matrices (10 x 10 elements each) as detectors gives the high spatial (200 x 200 microns/element with a 10 x objective) and temporal resolution (570 microseconds/frame). The recording system also includes a CCD camera for obtaining images of the preparation and overlaying the image with the optically detected signals. A software package has been developed for setting up the experimental protocol(s) and for collecting, processing, displaying, and analyzing the data in an user-friendly, windows-based environment.

Inter-rater agreement on identification of electrographic seizures and periodic discharges in ICU EEG recordings

OBJECTIVE This study investigated inter-rater agreement (IRA) among EEG experts for the identification of electrographic seizures and periodic discharges (PDs) in continuous ICU EEG recordings. METHODS Eight board-certified EEG experts independently identified seizures and PDs in thirty 1-h EEG segments which were selected from ICU EEG recordings collected from three medical centers. IRA was compared between seizure and PD identifications, as well as among rater groups that have passed an ICU EEG Certification Test, developed by the Critical Care EEG Monitoring Research Consortium (CCEMRC). RESULTS Both kappa and event-based IRA statistics showed higher mean values in identification of seizures compared to PDs (k=0.58 vs. 0.38; p<0.001). The group of rater pairs who had both passed the ICU EEG Certification Test had a significantly higher mean IRA in comparison to rater pairs in which neither had passed the test. CONCLUSIONS IRA among experts is significantly higher for identification of electrographic seizures compared to PDs. Additional instruction, such as the training module and certification test developed by the CCEMRC, could enhance this IRA. SIGNIFICANCE This study demonstrates more disagreement in the labeling of PDs in comparison to seizures. This may be improved by education about standard EEG nomenclature.

Familial posterior fossa arachnoid cyst.

BackgroundArachnoid cysts are a relatively common incidental finding on CT scans of the brain. They most commonly occur in the middle cranial fossa, where familial occurrence has rarely been reported. Posterior fossa arachnoid cysts are more unusual.Case historiesWe report the presence of quadrigeminal cistern arachnoid cysts in siblings.

Automatic Vagus Nerve Stimulation Triggered by Ictal Tachycardia: Clinical Outcomes and Device Performance - The U.S. E-37 Trial

The Automatic Stimulation Mode (AutoStim) feature of the Model 106 Vagus Nerve Stimulation (VNS) Therapy System stimulates the left vagus nerve on detecting tachycardia. This study evaluates performance, safety of the AutoStim feature during a 3‐5‐day Epilepsy Monitoring Unit (EMU) stay and long‐ term clinical outcomes of the device stimulating in all modes.

Diagnostic Accuracy of Electrographic Seizure Detection by Neurophysiologists and Non-Neurophysiologists in the Adult ICU Using a Panel of Quantitative EEG Trends.

Purpose: To evaluate the sensitivity and specificity of a panel of quantitative EEG (qEEG) trends for seizure detection in adult intensive care unit (ICU) patients when reviewed by neurophysiologists and non-neurophysiologists. Methods: One hour qEEG panels (n = 180) were collected retrospectively from 45 ICU patients and were distributed to 5 neurophysiologists, 7 EEG technologists, and 5 Neuroscience ICU nurses for evaluation of seizures. Each panel consisted of the following qEEG tools, displayed separately for left and right hemisphere electrodes: rhythmicity spectrogram (rhythmic run detection and display; Persyst Inc), color density spectral array, EEG asymmetry index, and amplitude integrated EEG. The reviewers did not have access to the raw EEG data. Results: For the reviewers ability to detect the presence of seizures on qEEG panels when compared with the gold standard of independent raw EEG review, the sensitivities and specificities are as follows: neurophysiologists 0.87 and 0.61, EEG technologists 0.80 and 0.80, and Neuroscience ICU nurses 0.87 and 0.61, respectively. There was no statistical difference among the three groups regarding sensitivity. Conclusions: Quantitative EEG display panels are a promising tool to aid detection of seizures by non-neurophysiologists as well as by neurophysiologists. However, even when used as a panel, qEEG trends do not appear to be adequate as the sole method for reviewing continuous EEG data.