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Biomedical subjects

J S George

Publications and source records attributed to J S George.

15 recordsLinked to original sources
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↗
PubMed1983

Control of Ca2+ in rod outer segment disks by light and cyclic GMP.

Photons absorbed in vertebrate rods and cones probably cause electrochemical changes at the photoreceptor plasma membrane by changing the cytoplasmic concentration of a diffusible transmitter substance, reducing the Na+ current flowing into the outer segment of the cell in the dark, to produce the observed membrane hyperpolarization that is the initial excitatory response. Cyclic GMP has been proposed as the transmitter because a light-activated cyclic GMP phosphodiesterase (PDE) has been found in rod disk membranes and because intracellularly injected cyclic GMP reduces rod membrane potentials. Free Ca2+ has also been proposed because increasing external [Ca2+] quickly and reversibly reduces the dark current and divalent cationophores increase the Ca2+ sensitivity. Ca2+ efflux from rod outer segments (ROS) of intact retinas occurs simultaneously with light responses. Vesicles prepared from ROS disk membranes become more permeable on illumination, releasing trapped ions or molecules, but intact outer segment disks have not previously been found to store sufficient Ca2+ in darkness and to release enough in light to meet the theoretical requirements for control of the dark current by varying cytoplasmic Ca2+ (refs 14-18). We now report experiments that show the required Ca2+ storage and release from rod disk membranes suspended in media containing high-energy phosphate esters and electrolytes approximating the cytoplasmic composition of live rod cells. Cyclic GMP stimulates Ca2+ uptake by ROS disks in such media.

Animals↗
PubMed1976

Intestinal parasitic infestation among parturients in Trinidad and Tobago.

1. In this limited survey, 42.5% of parturients were found to be infested with intestinal parasites. 2. Hookworm, Trichuris and Entamoeba infestations were the most common. 3. Race, social class and locality influenced in the incidence of the different types of infestations. 4. Those infested with hookworm had longer labor, smaller babies and higher incidence of prematurity.

Ascariasis↗
PubMedDate not supplied

Retinotopic organization of human visual cortex: departures from the classical model.

Retinotopic mapping strategies similar to those used for invasive electrophysiological studies to identify multiple visual areas in monkeys have been adapted for noninvasive studies in humans, using magnetic recordings of brain activity in conjunction with anatomical magnetic resonance imaging. The retinotopic organization of the primary visual area (V1) in the left hemisphere of human subjects was examined by presenting a small patterned stimuli near the vertical and horizontal meridians in the lower right visual field. In contrast with the classical model of V1 retinotopy, our results suggest that the representation of the horizontal meridian does not necessarily correspond in a one-to-one manner with the base of the calcarine fissure and that some lower field stimuli can activate regions in the lower bank of the fissure. The results also indicate significant individual variability in the details of how V1 maps around the calcarine fissure.

Brain Mapping↗