Epileptic event forewarning from scalp EEG.

The authors present a model-independent approach to quantify changes in the dynamics underlying nonlinear time-serial data. From time-windowed datasets, the authors construct discrete distribution functions on the phase space. Condition change between base case and test case distribution functions is assessed by dissimilarity measures via L1 distance and chi2 statistic. The discriminating power of these measures is first tested on noiseless data from the Lorenz and Bondarenko models, and is then applied to detecting dynamic change in multichannel clinical scalp EEG data. The authors compare the dissimilarity measures with the traditional nonlinear measures used in the analysis of chaotic systems. They also assess the potential usefulness of the new measures for robust, accurate, and timely forewarning of epileptic events.

Power frequency magnetic field exposure and gap junctional communication in Clone 9 cells.

Exposure to a power-frequency magnetic field has been reported to produce a statistically significant inhibition of gap junctional communication (GJC) in Clone 9 cells that have been pre-stressed by treatment with low concentrations of chloral hydrate (CH) [C.F. Blackman, J.P. Blanchard, S.G. Benane, D.E. House, J.A. Elder, Double blind test of magnetic field effects on neurite outgrowth, Bioelectromagnetics, 19 (1998) 204-209]. This observation might provide mechanistic insight into the possible role of electromagnetic fields (EMFs) in the carcinogenic process, since cancer cells frequently show decreased or absent GJC, and tumor promoting chemicals have been observed to inhibit GJC. Magnetic field exposure conditions were 45 Hz, 23.8 microT rms + parallel DC 36.6 microT, for 30 min of exposure. The responses of Clone 9 cells to the GJC-inhibiting effects of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate and the chemical CH were evaluated and compared to reported results [S.G. Benane, C.F. Blackman, D.E. House, Effects of perchloroethylene and its metabolites on intercellular communication in Clone 9 rat liver cells, J. Toxicol. Environ. Health, 48 (1996) 427-437]. Before magnetic field exposure, cells were exposed for 24 h to either 3 (nine experiments) or 5 mM (11 experiments) CH to produce GJC of 67% or 50%, respectively, relative to unexposed controls. GJC was assessed microscopically using the scrape-loading technique and a blinded protocol. No statistically significant effect was observed due to magnetic field exposure with either CH concentration.

Cellular communication in clone 9 cells exposed to magnetic fields.

Magnetic-field exposure (45 Hz B(a.c.) over a flux density range of 7.7 to 49.9 microT r.m.s. with parallel B(d.c.) of 36.6 microT) has been reported by Blackman and coworkers to inhibit gap junction intercellular communication in Clone 9 cells treated with chloral hydrate for 24 h prior to field exposure in accord with predictions of the ion parametric resonance model. The study reported here is an attempt to reproduce this effect. Baseline experiments showed that growth in culture and state of confluence at time of addition of chloral hydrate were comparable in both laboratories. PMA inhibited cell-cell communication in a dose-dependent manner, similar to the results of Blackman and coworkers, whereas cells in the present study were somewhat more sensitive to chloral hydrate than reported by Blackman and coworkers. A total of 38 exposure experiments were undertaken using a 45 Hz magnetic field with a flux density of 23.8 microT r.m.s., in parallel with a 36.6-microT static magnetic field for 40 to 45 min, after pretreatment with 2.5 mM chloral hydrate for 24 h. In 14 unblinded experiments, a small but statistically significant effect of magnetic-field exposure was observed, but due to the subjective nature of the assay, it was deemed essential to carry out blinded experiments. The remaining 24 experiments were blinded. In 15 blinded experiments, cells purchased from the American Type Culture Collection and grown only in this laboratory were used, while in 9 experiments, the cells had originally been grown in Blackman's laboratory and were subsequently sent to this laboratory. There was no statistically significant effect of magnetic-field exposure on gap junction intercellular communication in these blinded experiments using either cell line.

Timely detection of dynamical change in scalp EEG signals.

We present a robust, model-independent technique for quantifying changes in the dynamics underlying nonlinear time-serial data. After constructing discrete density distributions of phase-space points on the attractor for time-windowed data sets, we measure the dissimilarity between density distributions via L(1)-distance and chi(2) statistics. The discriminating power of the new measures is first tested on data generated by the Bondarenko "synthetic brain" model. We also compare traditional nonlinear measures and the new dissimilarity measures to detect dynamical change in scalp EEG data. The results demonstrate a clear superiority of the new measures in comparison to traditional nonlinear measures as robust and timely discriminators of changing dynamics. (c) 2000 American Institute of Physics.

Membrane potential and time requirements for detection of weak signals by voltage-gated ion channels.

The question of minimum detection limits for biological processes sensitive to membrane potential perturbations has arisen in various contexts. Of special interest are the prediction of theoretical limits for sensory perception processes and for possible biological effects of environmental or therapeutic electric and magnetic fields. A new method is presented here, addressing the particular case in which perturbations of membrane potential affect the gating rate probability of voltage-sensitive ion channels. Using a two-state model for channel gating, the influence of the perturbing potential on the mean fraction of open channels is approximated by a Boltzmann distribution, and integrated over time to obtain a quantity proportional to the net change in expected charge transfer through the membrane. This change in net charge transfer (the signal, S) is compared to the expected root mean variance in charge transfer (the noise, N) due to random channel gating. Using a nominal criterion of S/N = 1, a model is developed for predicting the minimum time and number of ion channels necessary to detect a given membrane potential. Example calculations, carried out for a gating charge of 6, indicate that a 1 microV induced membrane potential can be detected after 10 ms by an ensemble of less than 10(8) ion channels.

Studying electric field effects on embryonic myocytes.

Several problems arise when electrophysiological measurements are attempted on cells exposed to an electric field. In addition to field distortion produced by the reference electrode, membrane potential measurements by conventional microelectrode or patch-clamp techniques suffer serious interference from the applied field. We describe here a novel method for measurement of cardiac myocyte response to an alternating electric field that avoids these problems by sensing the mechanical activity of the cells rather than their electrical activity. A miniature electromechanical force transducer is used for this purpose. A glass pipet is attached to the force transducer, and only this pipet makes actual contact with the cell preparation. The resistive elements of the transducer are arranged as two legs of a Wheatstone bridge. Contractile activity of the cells produces small displacements of the micropipet and a resulting change in the transducer resistances. The Wheatstone bridge output is a current signal that is detected and converted to a voltage signal by a picoammeter before amplification and recording for later analysis. The technique may find applications in a variety of experimental studies of contractile tissues.

Low-cost system for real-time monitoring of luciferase gene expression.

In some mammalian cells transfected with luciferase reporter genes, the luciferase/luciferin reaction in a cell monolayer produces a very small light flux. While the low light levels are often measurable with single-photon counting cameras, these devices are expensive and may require long averaging times to acquire an image. We describe an approach for real-time monitoring of light produced by luciferase gene expression in intact, cultured cells using readily available and relatively inexpensive components. The system uses a single-photon counting photomultiplier tube with built-in high voltage supply and photon counting circuitry to rapidly measure average light output from growing cells in a 35 mm culture dish. The fast, accurate and highly sensitive response of the system makes it useful for studying the dynamics of gene expression over time periods ranging from minutes to days.