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John S George

Publications and source records attributed to John S George.

18 recordsLinked to original sources
PubMed2006

Dynamic neuroimaging of retinal light responses using fast intrinsic optical signals.

Transient intrinsic optical responses associated with neural activation offer an attractive strategy for dynamic imaging of neural activity, and may provide a noninvasive methodology for imaging of retinal function. Here we demonstrate the feasibility of near infrared imaging of fast intrinsic optical changes in isolated frog retina activated by visible light. Using a photodiode detector in a transmitted light geometry, we routinely measured dynamic transmitted optical responses in single passes, at the level of one part in 10(4) of background light. Rapid CCD image sequences acquired with transmitted light (bright field) illumination disclosed larger fractional responses and showed evidence of multiple response components with both negative- and positive-going signals with different timecourses. Dark field imaging further enhanced the contrast and sensitivity of optical measures of neural activation. High-resolution imaging disclosed optical responses in single pixels often exceeding 5%, of background light, allowing dynamic imaging at the resolution of single cells, in single passes. Fast optical signals are closely related to identified response components of the electroretinogram. Optical responses showed complex but consistent spatial organization from frame to frame. Our experimental results and theoretical analysis suggest that the optical responses may result from dynamic volume changes corresponding to ion and water flow across the cell membrane, directly associated with the electrophysiological response.

Animals↗
PubMed2006

See globally, spike locally: oscillations in a retinal model encode large visual features.

We show that coherent oscillations among neighboring ganglion cells in a retinal model encode global topological properties, such as size, that cannot be deduced unambiguously from their local, time-averaged firing rates. Whereas ganglion cells may fire similar numbers of spikes in response to both small and large spots, only large spots evoke coherent high frequency oscillations, potentially allowing downstream neurons to infer global stimulus properties from their local afferents. To determine whether such information might be extracted over physiologically realistic spatial and temporal scales, we analyzed artificial spike trains whose oscillatory correlations were similar to those measured experimentally. Oscillatory power in the upper gamma band, extracted on single-trials from multi-unit spike trains, supported good to excellent size discrimination between small and large spots, with performance improving as the number of cells and/or duration of the analysis window was increased. By using Poisson distributed spikes to normalize the firing rate across stimulus conditions, we further found that coincidence detection, or synchrony, yielded substantially poorer performance on identical size discrimination tasks. To determine whether size encoding depended on contiguity independent of object shape, we examined the total oscillatory activity across the entire model retina in response to random binary images. As the ON-pixel probability crossed the percolation threshold, which marks the sudden emergence of large connected clusters, the total gamma-band activity exhibited a sharp transition, a phenomena that may be experimentally observable. Finally, a reanalysis of previously published oscillatory responses from cat ganglion cells revealed size encoding consistent with that predicted by the retinal model.

Action Potentials↗
PubMed2006

Improving source detection and separation in a spatiotemporal Bayesian inference dipole analysis.

Most existing spatiotemporal multi-dipole approaches for MEG/EEG source localization assume that the dipoles are active for the full time range being analysed. If the actual time range of activity of sources is significantly shorter than the time range being analysed, the detectability, localization and time-course determination of such sources may be adversely affected, especially for weak sources. In order to improve detectability and reconstruction of such sources, it is natural to add active time range information (starting time point and ending time point of source activation) for each candidate source as unknown parameters in the analysis. However, this adds additional nonlinear free parameters that could burden the analysis and could be unfeasible for some methods. Recently, we described a spatiotemporal Bayesian inference multi-dipole analysis for the MEG/EEG inverse problem. This approach treated the number of dipoles as a free parameter, produced realistic uncertainty estimates using a Markov chain Monte Carlo numerical sampling of the posterior distribution and included a method to reduce the unwanted effects of local minima. In this paper, our spatiotemporal Bayesian inference multi-dipole analysis is extended to incorporate active time range parameters of starting and stopping time points. The properties of this analysis in comparison to the previous one without active time range parameters are demonstrated through extensive studies using both simulated and empirical MEG data.

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PubMed2005

Spatiotemporal Bayesian inference dipole analysis for MEG neuroimaging data.

Recently, we described a Bayesian inference approach to the MEG/EEG inverse problem that used numerical techniques to estimate the full posterior probability distributions of likely solutions upon which all inferences were based [Schmidt, D.M., George, J.S., Wood, C.C., 1999. Bayesian inference applied to the electromagnetic inverse problem. Human Brain Mapping 7, 195; Schmidt, D.M., George, J.S., Ranken, D.M., Wood, C.C., 2001. Spatial-temporal bayesian inference for MEG/EEG. In: Nenonen, J., Ilmoniemi, R. J., Katila, T. (Eds.), Biomag 2000: 12th International Conference on Biomagnetism. Espoo, Norway, p. 671]. Schmidt et al. (1999) focused on the analysis of data at a single point in time employing an extended region source model. They subsequently extended their work to a spatiotemporal Bayesian inference analysis of the full spatiotemporal MEG/EEG data set. Here, we formulate spatiotemporal Bayesian inference analysis using a multi-dipole model of neural activity. This approach is faster than the extended region model, does not require use of the subject's anatomical information, does not require prior determination of the number of dipoles, and yields quantitative probabilistic inferences. In addition, we have incorporated the ability to handle much more complex and realistic estimates of the background noise, which may be represented as a sum of Kronecker products of temporal and spatial noise covariance components. This reduces the effects of undermodeling noise. In order to reduce the rigidity of the multi-dipole formulation which commonly causes problems due to multiple local minima, we treat the given covariance of the background as uncertain and marginalize over it in the analysis. Markov Chain Monte Carlo (MCMC) was used to sample the many possible likely solutions. The spatiotemporal Bayesian dipole analysis is demonstrated using simulated and empirical whole-head MEG data.

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PubMed2005

Rapid optical coherence tomography and recording functional scattering changes from activated frog retina.

Optical coherence tomography (OCT) has important potential advantages for fast functional neuroimaging. However, dynamic neuroimaging poses demanding requirements for fast and stable acquisition of optical scans. Optical phase modulators based on the electro-optic effect allow rapid phase modulation; however, applications to low-coherence tomography are limited by the optical dispersion of a broadband light source by the electro-optic crystal. We show that the optical dispersion can be theoretically estimated and experimentally compensated. With an electro-optic phase modulator-based, no-moving-parts OCT system, near-infrared scattering changes associated with neural activation were recorded from isolated frog retinas activated by visible light.

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PubMed2005

Spatio-temporal mapping of rat whisker barrels with fast scattered light signals.

Optical techniques offer a number of potential advantages for imaging dynamic spatio-temporal patterns of activity in neural tissue. The methods provide the wide field of view required to image population activation across networks, while allowing resolution of the detailed structure of individual cells. Optical probes can provide high temporal resolution without penetrating the tissue surface. However, functional optical imaging has been constrained by the small size of the signals and the sluggish nature of the metabolic and hemodynamic responses that are the basis of most existing methods. Here, we employ both high-speed CCD cameras and high-sensitivity photodiodes to optimize resolution in both space and time, together with dark-field illumination in the near-infrared, to record fast intrinsic scattering signals from rat somatosensory cortex in vivo. Optical responses tracked the physiological activation of cortical columns elicited by single whisker twitches. High-speed imaging produced maps that were initially restricted in space to individual barrels, and then spread over time. Photodiode recordings disclosed 400-600 Hz oscillatory responses, tightly correlated in frequency and phase to those seen in simultaneous electrical recordings. Imaging based on fast intrinsic light scattering signals eventually could provide high resolution dynamic movies of neural networks in action.

Animals↗
PubMed2005

Cross-polarized reflected light measurement of fast optical responses associated with neural activation.

We developed an optical probe for cross-polarized reflected light measurements and investigated optical signals associated with electrophysiological activation in isolated lobster nerves. The cross-polarized baseline light intensity (structural signal) and the amplitude of the transient response to stimulation (functional signal) measured in reflected mode were dependent on the orientation of the nerve axis relative to the polarization plane of incident light. The maximum structural signal and functional response amplitude were observed at 45 degrees , and the ratio of functional to structural signals was approximately constant across orientations. Functional responses were measured in single trials in both transmitted and reflected geometries and responses had similar waveforms. Both structural and functional signals were an order of magnitude smaller in reflected than in transmitted light measurements, but functional responses had similar signal/noise ratios. We propose a theoretical model based on geometrical optics that is consistent with experimental results. In the model, the cross-polarized structural signal results from light reflection from axonal fibers and the transient functional response arises from axonal swelling associated with neural activation. Polarization-sensitive reflected light measurements could greatly enhance in vivo imaging of neural activation since cross-polarized responses are much larger than scattering signals now employed for dynamic functional neuroimaging.

Animals↗
PubMed2004

Simultaneous birefringence and scattered light measurements reveal anatomical features in isolated crustacean nerve.

Simultaneous fast birefringence and scattered light changes associated with crustacean nerve activation have different time courses and are produced by separate biophysical mechanisms. Technological advances in illumination, photodiodes and amplification circuitry achieved better signal-to-noise than earlier studies revealing optical signals in axonal nerve bundles as small as crayfish ventral cord and claw. The birefringence measurements yielded signals that could be observed in single trials, with temporally separated peaks associated with axonal populations of different diameters. A slit aperture placed perpendicular to the nerve reduced the spatial-temporal integration and enhanced the temporal structure of the separate peaks in the birefringence signal. Moving the slit aperture farther from the stimulation point delayed the signal in time, and also enhanced the separation between peaks. Different propagation velocities of the separate peaks provided evidence for at least three neuronal populations in the bundle. These studies underscore the advantages of birefringence over scattering measurements. Application of birefringence methods can optimize non-invasive imaging techniques being developed to detect fast optical responses associated with electrical neural activity in humans.

Animals↗
PubMed2004

Simultaneous magnetoencephalography and SQUID detected nuclear MR in microtesla magnetic fields.

A system that simultaneously measures magnetoencephalography (MEG) and nuclear magnetic resonance (NMR) signals from the human brain was designed and fabricated. A superconducting quantum interference device (SQUID) sensor coupled to a gradiometer pickup coil was used to measure the NMR and MEG signals. 1H NMR spectra with typical Larmor frequencies from 100-1000 Hz acquired simultaneously with the evoked MEG response from a stimulus to the median nerve are reported. The single SQUID gradiometer was placed approximately over the somatosensory cortex of a human subject to noninvasively record the signals. These measurements demonstrate, for the first time, the feasibility of simultaneous MRI and MEG. NMR in the microtesla regime provides narrow linewidths and the potential for high spatial resolution imaging, while SQUID sensors enable direct measurement of neuronal activity with high temporal resolution via MEG.

Humans↗
PubMed2004

SQUID detected NMR in microtesla magnetic fields.

We have built an NMR system that employs a superconducting quantum interference device (SQUID) detector and operates in measurement fields of 2-25 microT. The system uses a pre-polarizing field from 4 to 30 mT generated by simple room-temperature wire-wound coils that are turned off during measurements. The instrument has an open geometry with samples located outside the cryostat at room-temperature. This removes constraints on sample size and allows us to obtain signals from living tissue. We have obtained 1H NMR spectra from a variety of samples including water, mineral oil, and a live frog. We also acquired gradient encoded free induction decay (FID) data from a water-plastic phantom in the microT regime, from which simple projection images were reconstructed. NMR signals from samples inside metallic containers have also been acquired. This is possible because the penetration skin depth is much greater at the low operating frequencies of this system than for conventional systems. Advantages to ultra-low field NMR measurements include lower susceptibility artifacts caused by high strength polarizing and measurement fields, and negligible line width broadening due to measurement field inhomogeneity, reducing the burden of producing highly homogeneous fields.

Animals↗
PubMed2004

Stimulus-specific oscillations in a retinal model.

High-frequency oscillatory potentials (HFOPs) in the vertebrate retina are stimulus specific. The phases of HFOPs recorded at any given retinal location drift randomly over time, but regions activated by the same stimulus tend to remain phase locked with approximately zero lag, whereas regions activated by spatially separate stimuli are typically uncorrelated. Based on retinal anatomy, we previously postulated that HFOPs are mediated by feedback from a class of axon-bearing amacrine cells that receive excitation from neighboring ganglion cells-via gap junctions-and make inhibitory synapses back onto the surrounding ganglion cells. Using a computer model, we show here that such circuitry can account for the stimulus specificity of HFOPs in response to both high- and low-contrast features. Phase locking between pairs of model ganglion cells did not depend critically on their separation distance, but on whether the applied stimulus created a continuous path between them. The degree of phase locking between spatially separate stimuli was reduced by lateral inhibition, which created a buffer zone around strongly activated regions. Stimulating the inhibited region between spatially separate stimuli increased their degree of phase locking proportionately. Our results suggest several experimental strategies for testing the hypothesis that stimulus-specific HFOPs arise from axon-mediated feedback in the inner retina.

Action Potentials↗
PubMed2004

Correlated firing improves stimulus discrimination in a retinal model.

Synchronous firing limits the amount of information that can be extracted by averaging the firing rates of similarly tuned neurons. Here, we show that the loss of such rate-coded information due to synchronous oscillations between retinal ganglion cells can be overcome by exploiting the information encoded by the correlations themselves. Two very different models, one based on axon-mediated inhibitory feedback and the other on oscillatory common input, were used to generate artificial spike trains whose synchronous oscillations were similar to those measured experimentally. Pooled spike trains were summed into a threshold detector whose output was classified using Bayesian discrimination. For a threshold detector with short summation times, realistic oscillatory input yielded superior discrimination of stimulus intensity compared to rate-matched Poisson controls. Even for summation times too long to resolve synchronous inputs, gamma band oscillations still contributed to improved discrimination by reducing the total spike count variability, or Fano factor. In separate experiments in which neurons were synchronized in a stimulus-dependent manner without attendant oscillations, the Fano factor increased markedly with stimulus intensity, implying that stimulus-dependent oscillations can offset the increased variability due to synchrony alone.

Algorithms↗
PubMed2003

Optical lever recording of displacements from activated lobster nerve bundles and Nitella internodes.

An optical lever was designed for studying physical displacements associated with electrophysiological activation of lobster nerve bundles. Stimulation current pulses generated a compound action potential volley, and upward physical displacements of <1 nm were recorded. The swelling displacement propagated in the same direction as the action potential volley, occurred simultaneously with the action potentials, and required 10 ms to relax after the electrical potential was restored. For comparison with previous reports, we also recorded the displacement of Nitella internodes associated with electrical stimulation. We found that a rapid swelling displacement (approximately 10 nm) was followed by a larger, slow-shrinking displacement (approximately 100 nm).

Animals↗
PubMed2003

High-performance confocal system for microscopic or endoscopic applications.

We designed a high-performance confocal system that can be easily adapted to an existing light microscope or coupled with an endoscope for remote imaging. The system employs spatially and temporally patterned illumination produced by one of several mechanisms, including a micromirror array video projection device driven by a computer video source or a microlens array scanned by a piezo actuator in the microscope illumination path. A series of subsampled "component" video images are acquired from a solid-state video camera. Confocal images are digitally reconstructed using "virtual pinhole" synthetic aperture techniques applied to the collection of component images. Unlike conventional confocal techniques that raster scan a single detector and illumination point, our system samples multiple locations in parallel, with particular advantages for monitoring fast dynamic processes. We compared methods of patterned illumination and confocal image reconstruction by characterizing the point spread function, contrast, and intensity of imaged objects. Sample 3D reconstructions include a diatom and a Golgi-stained nerve cell collected in transmission.

Animals↗
PubMedDate not supplied

A theory of the Benham Top based on center-surround interactions in the parvocellular pathway.

A model color-opponent neuron was used to investigate the subjective colors evoked by the Benham Top (BT). Color-opponent inputs from cone-selective parvocellular (P) pathway neurons with center-surround receptive fields were subtracted with a short relative delay, yielding a small transient input in response to a white spot. This transient input was amplified by BT-like stimuli, modeled as a thin dark bar followed by full-field illumination. The narrow bar produced maximal activation of the P-pathway surrounds but only partial activation of the P-pathway centers. Due to saturation, subsequent removal of the bar had little effect on the P-pathway surrounds, whereas the transient input from the P-pathway centers was amplified via disinhibition. Responses to BT-like stimuli became weaker as surround sensitivity recovered, producing an effect analogous to the progression of perceived BT colors. Our results suggest that the BT-illusion arises because cone-selective neurons convey information about both color and luminance contrast, allowing the two signals become confounded.

Animals↗
PubMedDate not supplied

A model of high-frequency oscillatory potentials in retinal ganglion cells.

High-frequency oscillatory potentials (HFOPs) have been recorded from ganglion cells in cat, rabbit, frog, and mudpuppy retina and in electroretinograms (ERGs) from humans and other primates. However, the origin of HFOPs is unknown. Based on patterns of tracer coupling, we hypothesized that HFOPs could be generated, in part, by negative feedback from axon-bearing amacrine cells excited via electrical synapses with neighboring ganglion cells. Computer simulations were used to determine whether such axon-mediated feedback was consistent with the experimentally observed properties of HFOPs. (1) Periodic signals are typically absent from ganglion cell PSTHs, in part because the phases of retinal HFOPs vary randomly over time and are only weakly stimulus locked. In the retinal model, this phase variability resulted from the nonlinear properties of axon-mediated feedback in combination with synaptic noise. (2) HFOPs increase as a function of stimulus size up to several times the receptive-field center diameter. In the model, axon-mediated feedback pooled signals over a large retinal area, producing HFOPs that were similarly size dependent. (3) HFOPs are stimulus specific. In the model, gap junctions between neighboring neurons caused contiguous regions to become phase locked, but did not synchronize separate regions. Model-generated HFOPs were consistent with the receptive-field center dynamics and spatial organization of cat alpha cells. HFOPs did not depend qualitatively on the exact value of any model parameter or on the numerical precision of the integration method. We conclude that HFOPs could be mediated, in part, by circuitry consistent with known retinal anatomy.

Action Potentials↗
PubMedDate not supplied

Near-infrared imaging of fast intrinsic optical responses in visible light-activated amphibian retina.

High performance functional imaging is needed for dynamic measurements of neural processing in retina. Emerging techniques for visual prosthesis also require advanced methodology for reliable validation of electromagnetic stimulation of the retina. Imaging of fast intrinsic optical responses associated with neural activation promises a variety of technical advantages over traditional single and multichannel electrophysiological techniques for these purposes, but the application of fast optical signals for neural imaging has been limited by low signal-to-noise ratio and high background light intensity. However, by using an optimized near-infrared probe light and improved optical system, we improve the optical signals substantially, allowing single pass measurements with approximately micron resolution. We image fast intrinsic optical responses with different optical modalities, i.e., bright field, dark field, and cross-polarization, from isolated retina activated by visible light stimulation. At single cell resolution, bright-field imaging discloses the maxima of optical responses approximately 5% dI/I, where dI is the dynamic optical change and I is the baseline light intensity. Dark-field imaging techniques further enhance the sensitivity of optical measurements, and show the maxima of optical responses exceeding 10% dI/I. Cross-polarized imaging provides optical sensitivity similar to dark-field imaging, but different patterns of neural activation are observed.

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