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J S George

Publications and source records attributed to J S George.

At least 19 recordsLinked to original sources
PubMed2006

Dopaminergic modulation and rod contribution in the generation of oscillatory potentials in the tiger salamander retina.

The roles of rod and cone input and of dopamine in the generation of oscillatory potentials were studied in tiger salamander retina. Under scotopic conditions, oscillations were elicited with a green, but not a red stimulus. With mesopic background illumination, both stimuli caused oscillations. Addition of quinpirole to a mesopic retina eliminated oscillations while SKF-38393 had no effect. Similarly, addition of sulpiride to a light-adapted retina elicited oscillatory activity, but SCH 22390 had no effect. These results suggest that oscillatory potentials are elicited through activation of the rod pathway and are modulated by dopamine through D2-receptors.

Adaptation, Physiological↗
PubMed2004

Simultaneously detected biomagnetic signals and NMR.

We have obtained 1H NMR spectra simultaneously with high temporal resolution biomagnetic signals such as the magnetocardiogram (MCG) and magnetomyogram (MMG). The NMR spectra are acquired at measurement fields of 2-50 microT, with corresponding proton Larmor frequencies of 80-2000 Hz. Our measurements demonstrate a method suitable for MR imaging with concurrent measurement of biomagnetic signals that can provide sub-millisecond temporal resolution. The narrow line widths, reduction in susceptibility noise and enhanced spectral resolution at ultra low fields provide a new and extremely sensitive measurement method that may enable direct imaging of biological currents by detecting the phase or frequency shifts produced by magnetic fields arising from those currents. The results of our simultaneous measurements of NMR with MCG and MMG are compared to results from a current phantom to investigate the exciting potential of direct MRI of bioelectric currents.

Electrocardiography↗
PubMed2004

MUSIC seeded multi-dipole MEG modeling using the Constrained Start Spatio-Temporal modeling procedure.

The Constrained Start Spatio-Temporal modeling program (CSST) is an objective multi-dipole, multi-start MEG/EEG analysis procedure that randomly selects from 100 to 100,000 initial dipole configurations, and runs a nonlinear simplex search on each of these configurations employing a reduced Chi-square statistic as the minimization criterion, to obtain a set of dipole configurations that best fit the data [Ranken, 2002]. A parallel version of CSST is implemented in IDL and MPI, making CSST usable on a single computer, or on a Linux cluster. We have now developed a multi-resolution version of MUSIC [Mosher, 1992] [Mosher, 1998] that provides an 80% or more reduction in the number of forward calculations needed to obtain results comparable to a 160,000 point MUSIC scan, on a 2 mm grid that defines a brain volume. The multi-resolution MUSIC scan provides an improved set of initial dipole estimates for the CSST analysis. In preliminary tests on real and simulated MEG data, with model orders ranging between 5 and 7 dipoles, the best performance improvements were obtained by mixing in 1 to 3 dipole locations randomly drawn from the best MUSIC locations, with randomly selected locations from the brain volume to complete the selected model order. We have also developed an improved method for sampling the brain volume for initial configurations. These improvements have led to a 75% reduction in the number of starting configurations required to obtain 5-10 best solutions with equal or lower reduced Chi-square values, when compared to the best solutions from the previous version of CSST.

Algorithms↗
PubMed2002

The influence of brain tissue anisotropy on human EEG and MEG.

The influence of gray and white matter tissue anisotropy on the human electroencephalogram (EEG) and magnetoencephalogram (MEG) was examined with a high resolution finite element model of the head of an adult male subject. The conductivity tensor data for gray and white matter were estimated from magnetic resonance diffusion tensor imaging. Simulations were carried out with single dipoles or small extended sources in the cortical gray matter. The inclusion of anisotropic volume conduction in the brain was found to have a minor influence on the topology of EEG and MEG (and hence source localization). We found a major influence on the amplitude of EEG and MEG (and hence source strength estimation) due to the change in conductivity and the inclusion of anisotropy. We expect that inclusion of tissue anisotropy information will improve source estimation procedures.

Adult↗
PubMed2001

Conductivity tensor mapping of the human brain using diffusion tensor MRI.

Knowledge of the electrical conductivity properties of excitable tissues is essential for relating the electromagnetic fields generated by the tissue to the underlying electrophysiological currents. Efforts to characterize these endogenous currents from measurements of the associated electromagnetic fields would significantly benefit from the ability to measure the electrical conductivity properties of the tissue noninvasively. Here, using an effective medium approach, we show how the electrical conductivity tensor of tissue can be quantitatively inferred from the water self-diffusion tensor as measured by diffusion tensor magnetic resonance imaging. The effective medium model indicates a strong linear relationship between the conductivity and diffusion tensor eigenvalues (respectively, final sigma and d) in agreement with theoretical bounds and experimental measurements presented here (final sigma/d approximately 0.844 +/- 0.0545 S small middle dots/mm(3), r(2) = 0.945). The extension to other biological transport phenomena is also discussed.

Brain↗
PubMed2001

Continuous image and electrophysiological recording with real-time processing and control.

Collecting continuous video together with multichannel electrophysiological data and other experimental modalities requires high bandwidth and storage capacities, as well as accurate synchronization to detect correlations between different recorded events. Often, experiments are highly complex, with many variables requiring immediate analysis and feedback during the course of the experiment. In addition, output channels require real-time control with high time resolution. We have explored several approaches to a system that can perform the above functions. The design of our system considered a number of issues, including time intervals between control and acquisition events, longest continuous recording period, data transfer bottleneck considerations, file archiving and format, and real-time display and processing. To demonstrate the system, we describe an experiment for characterizing rapid evoked scattered light changes in neural tissue, in vivo, using simultaneous electronic image acquisition and electrophysiological recording.

Animals↗
PubMed2001

Scattered-light imaging in vivo tracks fast and slow processes of neurophysiological activation.

We imaged fast optical changes associated with evoked neural activation in the dorsal brainstem of anesthetized rats, using a novel imaging device. The imager consisted of a gradient-index (GRIN) lens, a microscope objective, and a miniature charged-coupled device (CCD) video camera. We placed the probe in contact with tissue above cardiorespiratory areas of the nucleus of the solitary tract and illuminated the tissue with 780-nm light through flexible fibers around the probe perimeter. The focus depth was adjusted by moving the camera and microscope objective relative to the fixed GRIN lens. Back-scattered light images were relayed through the GRIN lens to the CCD camera. Video frames were digitized at 100 frames per second, along with tracheal pressure, arterial blood pressure, and electrocardiogram signals recorded at 1 kHz per channel. A macroelectrode placed under the GRIN lens recorded field potentials from the imaged area. Aortic, vagal, and superior laryngeal nerves were dissected free of surrounding tissue within the neck. Separate shocks to each dissected nerve elicited evoked electrical responses and caused localized optical activity patterns. The optical response was modeled by four distinct temporal components corresponding to putative physical mechanisms underlying scattered light changes. Region-of-interest analysis revealed image areas which were dominated by one or more of the different time-course components, some of which were also optimally recorded at different tissue depths. Two slow optical components appear to correspond to hemodynamic responses to metabolic demand associated with activation. Two fast optical components paralleled electrical evoked responses.

Airway Resistance↗
PubMed1999

A focusing image probe for assessing neural activity in vivo.

We describe a compact, focusing image probe to record rapid optical changes from neural tissue. A gradient index (GRIN) lens served as a relay lens from tissue to a microscope objective which projected an image onto a CCD camera. The microscope objective and camera assembly was adjusted independently from the GRIN lens, allowing focus changes without disturbing the probe/tissue interface; firm contact minimized movement and specular reflectance. Fiber optics around the probe perimeter provided diffuse illumination from a 780 nm laser, or 660 and 560 nm light emitting diodes. To characterize depth-of-field, we imaged a black suture through increasing tissue thicknesses. Light modulation by the suture remained detectable down to 900 microm using 780 nm illumination. We acquired images from cardiorespiratory areas of the rat dorsal medulla, at different depths and illumination wavelengths. Images illuminated at 560 nm were dominated by vasculature flow patterns, while 660 nm illumination revealed different spatial patterns which preceded vascular flow by 40 ms and may represent cardiac-related neural activity. Using 780 nm light, image sequences triggered by the cardiac R-wave showed vascular perfusion changes with delayed and broader responses at deeper levels. Electrical stimulation within the vagal bundle caused fast optical changes which track the electrical response, with a different spatial distribution from hemodynamic signals.

Animals↗
PubMed1999

Bayesian inference applied to the electromagnetic inverse problem.

We present a new approach to the electromagnetic inverse problem that explicitly addresses the ambiguity associated with its ill-posed character. Rather than calculating a single "best" solution according to some criterion, our approach produces a large number of likely solutions that both fit the data and any prior information that is used. Whereas the range of the different likely results is representative of the ambiguity in the inverse problem even with prior information present, features that are common across a large number of the different solutions can be identified and are associated with a high degree of probability. This approach is implemented and quantified within the formalism of Bayesian inference, which combines prior information with that of measurement in a common framework using a single measure. To demonstrate this approach, a general neural activation model is constructed that includes a variable number of extended regions of activation and can incorporate a great deal of prior information on neural current such as information on location, orientation, strength, and spatial smoothness. Taken together, this activation model and the Bayesian inferential approach yield estimates of the probability distributions for the number, location, and extent of active regions. Both simulated MEG data and data from a visual evoked response experiment are used to demonstrate the capabilities of this approach.

Bayes Theorem↗
PubMed1995

Neuromagnetic source imaging with FOCUSS: a recursive weighted minimum norm algorithm.

The paper describes a new algorithm for tomographic source reconstruction in neural electromagnetic inverse problems. Termed FOCUSS (FOCal Underdetermined System Solution), this algorithm combines the desired features of the two major approaches to electromagnetic inverse procedures. Like multiple current dipole modeling methods, FOCUSS produces high resolution solutions appropriate for the highly localized sources often encountered in electromagnetic imaging. Like linear estimation methods, FOCUSS allows current sources to assume arbitrary shapes and it preserves the generality and ease of application characteristic of this group of methods. It stands apart from standard signal processing techniques because, as an initialization-dependent algorithm, it accommodates the non-unique set of feasible solutions that arise from the neuroelectric source constraints. FOCUSS is based on recursive, weighted norm minimization. The consequence of the repeated weighting procedure is, in effect, to concentrate the solution in the minimal active regions that are essential for accurately reproducing the measurements. The FOCUSS algorithm is introduced and its properties are illustrated in the context of a number of simulations, first using exact measurements in 2- and 3-D problems, and then in the presence of noise and modeling errors. The results suggest that FOCUSS is a powerful algorithm with considerable utility for tomographic current estimation.

Algorithms↗
PubMed1995

Mapping function in the human brain with magnetoencephalography, anatomical magnetic resonance imaging, and functional magnetic resonance imaging.

Integrated analyses of human anatomical and functional measurements offer a powerful paradigm for human brain mapping. Magnetoencephalography (MEG) and EEG provide excellent temporal resolution of neural population dynamics as well as capabilities for source localization. Anatomical magnetic resonance imaging (MRI) provides excellent spatial resolution of head and brain anatomy, whereas functional MRI (fMRI) techniques provide an alternative measure of neural activation based on associated hemodynamic changes. These methodologies constrain and complement each other and can thereby improve our interpretation of functional neural organization. We have developed a number of computational tools and techniques for the visualization, comparison, and integrated analysis of multiple neuroimaging techniques. Construction of geometric anatomical models from volumetric MRI data allows improved models of the head volume conductor and can provide powerful constraints for neural electromagnetic source modeling. These approaches, coupled to enhanced algorithmic strategies for the inverse problem, can significantly enhance the accuracy of source-localization procedures. We have begun to apply these techniques for studies of the functional organization of the human visual system. Such studies have demonstrated multiple, functionally distinct visual areas that can be resolved on the basis of their locations, temporal dynamics, and differential sensitivity to stimulus parameters. Our studies have also produced evidence of internal retinotopic organization in both striate and extrastriate visual areas but have disclosed organizational departures from classical models. Comparative studies of MEG and fMRI suggest a reasonable but imperfect correlation between electrophysiological and hemodynamic responses. We have demonstrated a method for the integrated analysis of fMRI and MEG, and we outline strategies for improvement of these methods. By combining multiple measurement techniques, we can exploit the complementary strengths and transcend the limitations of the individual neuro-imaging methods.

Brain↗
PubMed1995

Temporal dynamics of visual-evoked neuromagnetic sources: effects of stimulus parameters and selective attention.

Results are reviewed from several neuromagnetic studies which characterize the temporal dynamics of neural sources contributing to the visual evoked response and effects of attention on these sources. Different types of pattern-onset stimuli (< or = 2 degrees) were presented sequentially to a number of field locations in the right visual field. Multiple dipole models were applied to a sequence of instantaneous field distributions constructed at 10 ms intervals. Best-fitting source parameters were superimposed on Magnetic Resonance images (MRI) of each subject to identify the anatomical structure(s) giving rise to the surface patterns. At least three sources, presumably corresponding to different visual areas, were routinely identified from 80-150 ms following the onset of visual stimulation. This observation was consistent across subjects and studies. The temporal sequence and strength of activation of these sources, however, were dependent upon the specific stimulus parameters used to evoke the response (e.g., eccentricity) and on the relevance of the stimulus to the subject. In addition, our results provide evidence for the recurrence of activity in striate and extrastriate regions, following the initial cycle of responses.

Adult↗
PubMed1993

Reversible opening of the blood-brain barrier by anti-bacterial antibodies.

The leukocyte adhesion molecule CR3 (CD11b/CD18, Mac-1) promotes leukocyte transmigration into tissues by engaging an unknown cognate ligand on the surface of vascular endothelial cells. Filamentous hemagglutinin (FHA), an adhesin of the bacterium Bordetella pertussis, binds to CR3. We hypothesized that FHA mimics the native ligand for the CR3 integrin on endothelial cells and predicted that anti-FHA antibodies should bind to endothelial cells, interfere with leukocyte recruitment, and induce endothelial permeability. Anti-FHA monoclonal antibodies bound to cerebral microvessels in sections from human brain and upon intravenous injection into rabbits. Antibody binding correlated with the ability to recognize two polypeptides in extracts of human cerebral vessels that were also bound by CD18. In vivo, antibody binding not only interfered with transmigration of leukocytes into cerebrospinal fluid but also induced a dose-dependent reversible increase in blood-brain barrier permeability sufficient to improve delivery of intravenously administered therapeutic agents to brain parenchyma.

Animals↗
PubMed1990

Interactions between the subunits of transducin and cyclic GMP phosphodiesterase in Rana catesbiana rod photoreceptors.

In bullfrog (Rana catesbiana) rods the activity of cyclic GMP (cGMP) phosphodiesterase was stimulated 10 times by washing disc membranes with an isotonic, GTP-containing buffer. This stimulation was maintained following hydrolysis of GTP and after removal of guanine nucleotides. At least 60-70% of the inhibitory gamma subunit of cGMP phosphodiesterase (P gamma) was physically released from membranes by these washing procedures. When cGMP phosphodiesterase was activated by a hydrolysis-resistant GTP analogue, P gamma was found in the supernatant complexed with the transducin alpha subunit (T alpha) using three chromatography systems. When GTP was used to activate cGMP phosphodiesterase, P gamma was also found in the supernatant complexed with GDP.T alpha. This complex was also isolated using the same three chromatography systems, indicating that P gamma remained tightly bound to T alpha even after bound GTP was hydrolyzed. Interaction with the beta,gamma subunits of transducin, which remained associated with disc membranes, was required for the release of P gamma from the GDP.T alpha complex, which resulted in the deactivation of active cGMP phosphodiesterase. We conclude that during activation of cGMP phosphodiesterase, P gamma is complexed with T alpha (both GTP and GDP forms) in the supernatant and that, following GTP hydrolysis, beta,gamma subunits of transducin are necessary for the release of P gamma from the complex and the resulting inactivation of cGMP phosphodiesterase in frog photoreceptors.

3',5'-Cyclic-GMP Phosphodiesterases↗