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Differential activation of cerebral blood flow by stimulating amblyopic and fellow eye.

PURPOSE: Positron emission tomography (PET), the blood flow response in the primary visual cortex (V1) to two visual stimuli, low temporal frequency (6 Hz) to activate the parvocellular system, and high temporal frequency (25 Hz) to activate the magnocellular system were used to investigate pathophysiologic mechanism of amblyopia. METHODS: Five women and one man who were aged between 26 and 60 years, who were ophthalmologically normal except for amblyopia, and who had corrected visual acuity in the amblyopic eye of 0.6 or worse were examined. An intravenous injection of the H(2)(15)O was given, and the regional cerebral blood flow was measured by PET during full-field stimulation with either 6 Hz or 25 Hz flicker to the amblyopic or the sound eye. RESULT: The activation of blood flow in the contra-lateral area V1 by the 6-Hz stimulation of the sound eye was greater than that during the stimulation of the amblyopic eye (P<0.05, small volume correction, n=6). With 25-Hz stimulation of the sound and amblyopic eyes, the blood flow in the contra-lateral and ipsi-lateral areas V1 was not significantly different. CONCLUSION: The decreased activation of blood flow in the contra-lateral V1 by low temporal frequency stimuli supports the hypothesis that the parvocellular pathway in amblyopic eyes is depressed.

Adult↗

Subretinal implantation and testing of polyimide film electrodes in cats.

BACKGROUND: Progress in the field of microelectronics has led to the development of visual prostheses for the treatment of blinding diseases. One concept under investigation is an electronic subretinal prosthesis to replace the function of lost photoreceptors in degenerative diseases, such as retinitis pigmentosa. METHODS: In the subretinal prosthesis design concept, an array of stimulation electrodes is placed in the subretinal space. To test the feasibility of the concept and to determine basic stimulation parameters, wire-bound stimulation devices were used in acute trials for up to 12 h in three eyes in anaesthetised cats. These wire-bound stimulation elements were based on strips of polyimide film. The film strips were introduced through a sclerostomy into the vitreous cavity and via a retinotomy into the subretinal space during a modification of the standard three-port vitrectomy procedure. On entry through the retinotomy, the film was advanced mechanically to the desired position in the area centralis. Perfluorocarbon liquid (PFCL) was used to establish close contact between the electrode array and the outer retina. Stimulation was performed with computer-generated sequences of current waveforms in acute trials immediately after surgical implantation of the stimulation film. Cortical recordings in the primary visual cortex were performed with electrodes placed in locations corresponding to the retinal stimulus site. RESULTS: All three implantations were carried out successfully with the stimulation array implanted beneath the outer retina of the area centralis of the operated eye. The retina was attached over the stimulation array in all cases. No cortical responses were recorded in one of the stimulation sessions. The results from another session revealed clear intracortical responses to subretinal stimulation with polyimide films. Following single-site retina stimulation, the estimates of spatial cortical resolution and temporal resolution were approximately 1 mm and 20-50 ms, respectively. DISCUSSION: Our results indicate that focal subretinal stimulation evokes localised spatio-temporal distribution of cortical responses. These findings offer hope that coarse restoration of vision may be feasible by subretinal electrical stimulation.

Animals↗

Scene segmentation by spike synchronization in reciprocally connected visual areas. I. Local effects of cortical feedback.

To investigate scene segmentation in the visual system we present a model of two reciprocally connected visual areas using spiking neurons. Area P corresponds to the orientation-selective subsystem of the primary visual cortex, while the central visual area C is modeled as associative memory representing stimulus objects according to Hebbian learning. Without feedback from area C, a single stimulus results in relatively slow and irregular activity, synchronized only for neighboring patches (slow state), while in the complete model activity is faster with an enlarged synchronization range (fast state). When presenting a superposition of several stimulus objects, scene segmentation happens on a time scale of hundreds of milliseconds by alternating epochs of the slow and fast states, where neurons representing the same object are simultaneously in the fast state. Correlation analysis reveals synchronization on different time scales as found in experiments (designated as tower, castle, and hill peaks). On the fast time scale (tower peaks, gamma frequency range), recordings from two sites coding either different or the same object lead to correlograms that are either flat or exhibit oscillatory modulations with a central peak. This is in agreement with experimental findings, whereas standard phase-coding models would predict shifted peaks in the case of different objects.

Animals↗

Scene segmentation by spike synchronization in reciprocally connected visual areas. II. Global assemblies and synchronization on larger space and time scales.

We present further simulation results of the model of two reciprocally connected visual areas proposed in the first paper [Knoblauch and Palm (2002) Biol Cybern 87:151-167]. One area corresponds to the orientation-selective subsystem of the primary visual cortex, the other is modeled as an associative memory representing stimulus objects according to Hebbian learning. We examine the scene-segmentation capability of our model on larger time and space scales, and relate it to experimental findings. Scene segmentation is achieved by attention switching on a time-scale longer than the gamma range. We find that the time-scale can vary depending on habituation parameters in the range of tens to hundreds of milliseconds. The switching process can be related to findings concerning attention and biased competition, and we reproduce experimental poststimulus time histograms (PSTHs) of single neurons under different stimulus and attentional conditions. In a larger variant the model exhibits traveling waves of activity on both slow and fast time-scales, with properties similar to those found in experiments. An apparent weakness of our standard model is the tendency to produce anti-phase correlations for fast activity from the two areas. Increasing the inter-areal delays in our model produces alternations of in-phase and anti-phase oscillations. The experimentally observed in-phase correlations can most naturally be obtained by the involvement of both fast and slow inter-areal connections; e.g., by two axon populations corresponding to fast-conducting myelinated and slow-conducting unmyelinated axons.

Animals↗

A rotation and translation invariant discrete saliency network.

We describe a neural network that enhances and completes salient closed contours in images. Our work is different from all previous work in three important ways. First, like the input provided to primary visual cortex (V1) by the lateral geniculate nucleus (LGN), the input to our computation is isotropic. That is, it is composed of spots, not edges. Second, our network computes a well-defined function of the input based on a distribution of closed contours characterized by a random process. Third, even though our computation is implemented in a discrete network, its output is invariant to continuous rotations and translations of the input image.

Neural Networks, Computer↗

Is sparse and distributed the coding goal of simple cells?

The question of why the receptive fields of simple cells in the primary visual cortex are Gabor-like is a crucial one in vision research. Many research efforts (Olshausen and Field 1996, 1997; van Hateren and Ruderman 1998; van Hateren and van der Schaaf 1998) that yield a set of localized, oriented, and bandpass Gabor-like receptive fields believe that sparse and distributed is the coding goal of simple cells. This paper investigates a more general coding strategy that measures equally any departure from normality in the simple cells' responses. That is, we investigate the possibility that highly kurtotic response histograms may result if simple cells explicitly seek, not maximally kurtotic, but rather maximally non-Gaussian response histograms to natural images. It is found that, under this coding strategy, the simulations produce a majority of localized, oriented, bandpass (Gabor-like) receptive fields. Some receptive fields, however, are spatially distributed and show little oriented structure. Nearly all receptive fields, regardless of whether they are Gabor-like or non-Gabor-like, yield highly kurtotic response histograms to natural images. Thus, in seeking maximally non-Gaussian response histograms, receptive fields spontaneously yield highly kurtotic histograms. The presence in our ensemble of nonlocalized, nonoriented receptive fields may be due to the artificial requirement that receptive fields be orthonormal. We conclude that the high kurtoses observed in the response histograms of simple-cell receptive fields to natural images may reflect a property of natural images themselves rather than an explicit coding goal used to structure simple-cell receptive fields.

Action Potentials↗

Spontaneous symmetry breaking in self-organizing neural fields.

We extend the theory of self-organizing neural fields in order to analyze the joint emergence of topography and feature selectivity in primary visual cortex through spontaneous symmetry breaking. We first show how a binocular one-dimensional topographic map can undergo a pattern forming instability that breaks the underlying symmetry between left and right eyes. This leads to the spatial segregation of eye specific activity bumps consistent with the emergence of ocular dominance columns. We then show how a 2-dimensional isotropic topographic map can undergo a pattern forming instability that breaks the underlying rotation symmetry. This leads to the formation of elongated activity bumps consistent with the emergence of orientation preference columns. A particularly interesting property of the latter symmetry breaking mechanism is that the linear equations describing the growth of the orientation columns exhibits a rotational shift-twist symmetry, in which there is a coupling between orientation and topography. Such coupling has been found in experimentally generated orientation preference maps.

Algorithms↗

A mathematical model of activity-dependent, anatomical segregation induced by competition for neurotrophic support.

Mathematical or computational models of activity-dependent neural competition typically impose competition in anatomically fixed networks by the use of synaptic normalisation, for which there is very little experimental support. Recent experimental evidence, however, strongly implicates neurotrophic factors in neural plasticity and competition, in addition to their well-known potent effects on neurite outgrowth and synaptogenesis. We therefore present a simple, mathematical model of anatomical segregation induces by activity-dependent competition for a limited supply of a neurotrophic factor provided by target cells to afferents. We extract the behaviour of the model in various regimes, in which the neurotrophic factor is either in critical supply or in abundant supply, by a combination of analytical and numerical methods, and study the effects of correlations in afferent inputs on competition. We apply the model to three different systems: ocular dominance column formation; elimination of polyneuronal innervation at the vertebrate neuromuscular junction; trigeminal brain stem whisker-related structure formation. Several classes of related predictions emerge, including the prediction that kittens reared with strabismus should require a higher concentration of neurotrophic factor infusion into their primary visual cortex than normally reared cats in order to induce the anatomical desegregation of ocular dominance columns. We also speculate on the mechanisms of support of inhibitory rather than excitatory neurons, and suggest the existence of a separate, (Cl-)-mediated activity-dependent pathway for their neurotrophic support.

Animals↗

Formation of a direction map by projection learning using Kohonen's self-organization map.

In this paper, we propose a modification of Kohonen's self-organization map (SOM) algorithm. When the input signal space is not convex, some reference vectors of SOM can protrude from it. The input signal space must be convex to keep all the reference vectors fixed on it for any updates. Thus, we introduce a projection learning method that fixes the reference vectors onto the input signal space. This version of SOM can be applied to a non-convex input signal space. We applied SOM with projection learning to a direction map observed in the primary visual cortex of area 17 of ferrets, and area 18 of cats. Neurons in those areas responded selectively to the orientation of edges or line segments, and their directions of motion. Some iso-orientation domains were subdivided into selective regions for the opposite direction of motion. The abstract input signal space of the direction map described in the manner proposed by Obermayer and Blasdel [(1993) J Neurosci 13: 4114-4129] is not convex. We successfully used SOM with projection learning to reproduce a direction-orientation joint map.

Algorithms↗

The psychophysics of perceptual memory.

Psychophysical studies of short-term memory for attributes or dimensions of the visual stimulus known to be important in early visual processing--spatial frequency, orientation, contrast, motion--identify an early perceptual memory system. The proposed system, which may be part of the Schacter-Tulving perceptual representation system (PRS), is located early in the visual processing stream, prior to the structural description system responsible for shape priming but beyond primary visual cortex (V1), and consists of a series of parallel special-purpose perceptual mechanisms with independent but limited processing resources, where each mechanism is devoted to the analysis of a single stimulus dimension and is coupled to a memory store. The experimental evidence for this hypothesis is reviewed.

Evoked Potentials↗

Multivariate objective response detectors (MORD): statistical tools for multichannel EEG analysis during rhythmic stimulation.

The presence of cerebral evoked responses can be tested by using objective response detectors. They are statistical tests that provide a threshold above which responses can be assumed to have occurred. The detection power depends on the signal-to-noise ratio (SNR) of the response and the amount of data available. However, the correlation within the background noise could also affect the power of such detectors. For a fixed SNR, the detection can only be improved at the expense of using a longer stretch of signal. This can constitute a limitation, for instance, in monitored surgeries. Alternatively, multivariate objective response detection (MORD) could be used. This work applies two MORD techniques (multiple coherence and multiple component synchrony measure) to EEG data collected during intermittent photic stimulation. They were evaluated throughout Monte Carlo simulations, which also allowed verifying that correlation in the background reduces the detection rate. Considering the N EEG derivations as close as possible to the primary visual cortex, if N = 4, 6 or 8, multiple coherence leads to a statistically significant higher detection rate in comparison with multiple component synchrony measure. With the former, the best performance was obtained with six signals (O1, O2, T5, T6, P3 and P4).

Acoustic Stimulation↗

The influence of cortical feature maps on the encoding of the orientation of a short line.

The inhomogeneous distribution of the receptive fields of cortical neurons influences the cortical representation of the orientation of short lines seen in visual images. We construct a model of the response of populations of neurons in the human primary visual cortex by combining realistic response properties of individual neurons and cortical maps of orientation and location preferences. The encoding error, which characterizes the difference between the parameters of a visual stimulus and their cortical representation, is calculated using Fisher information as the square root of the variance of a statistically efficient estimator. The error of encoding orientation varies considerably with the location and orientation of the short line stimulus as modulated by the underlying orientation preference map. The average encoding error depends only weakly on the structure of the orientation preference map and is much smaller than the human error of estimating orientation measured psychophysically. From this comparison we conclude that the actual mechanism of orientation perception does not make efficient use of all the information available in the neuronal responses and that it is the decoding of visual information from neuronal responses that limits psychophysical performance.

Action Potentials↗

Fast numerical methods for simulating large-scale integrate-and-fire neuronal networks.

We discuss numerical methods for simulating large-scale, integrate-and-fire (I&F) neuronal networks. Important elements in our numerical methods are (i) a neurophysiologically inspired integrating factor which casts the solution as a numerically tractable integral equation, and allows us to obtain stable and accurate individual neuronal trajectories (i.e., voltage and conductance time-courses) even when the I&F neuronal equations are stiff, such as in strongly fluctuating, high-conductance states; (ii) an iterated process of spike-spike corrections within groups of strongly coupled neurons to account for spike-spike interactions within a single large numerical time-step; and (iii) a clustering procedure of firing events in the network to take advantage of localized architectures, such as spatial scales of strong local interactions, which are often present in large-scale computational models-for example, those of the primary visual cortex. (We note that the spike-spike corrections in our methods are more involved than the correction of single neuron spike-time via a polynomial interpolation as in the modified Runge-Kutta methods commonly used in simulations of I&F neuronal networks.) Our methods can evolve networks with relatively strong local interactions in an asymptotically optimal way such that each neuron fires approximately once in [Formula: see text] operations, where N is the number of neurons in the system. We note that quantifications used in computational modeling are often statistical, since measurements in a real experiment to characterize physiological systems are typically statistical, such as firing rate, interspike interval distributions, and spike-triggered voltage distributions. We emphasize that it takes much less computational effort to resolve statistical properties of certain I&F neuronal networks than to fully resolve trajectories of each and every neuron within the system. For networks operating in realistic dynamical regimes, such as strongly fluctuating, high-conductance states, our methods are designed to achieve statistical accuracy when very large time-steps are used. Moreover, our methods can also achieve trajectory-wise accuracy when small time-steps are used.

Algorithms↗

Dynamic changes in the tuning of striate neurons to the shapes of cross-shaped figures.

Time slice analysis was used to study the dynamics of tuning to the shapes of cross-shaped figures flashing in the receptive fields of 83 neurons in the primary visual cortex (field 17) of the cat brain. Tuning was assessed in terms of the numbers of spikes in the overall response and its sequential 20-msec fragments. Only 11.7% of neurons produced reproducibly developing spike responses to a given shape (defined as the angle between the lines), i.e., had a preferred cross-shaped figure. In the remaining cases (88.3%), tuning of neurons to the shape of the cross showed dynamic changes. In 7.2% of cases, changes in the preferred shape of the cross occurred monophasically; changes were biphasic in 27.0% of cases, while in the remaining 54.1% of cases, the dynamics in changes in the preferred cross shape were undulatory. The tuning of receptive field zones is assessed as the cause of these effects and their difference from the previously observed dynamics of preferred orientations of single bars and cross-shaped figures; the functional significance of these effects is also discussed.

Action Potentials↗

Cortico-thalamo-cortical projection between visual cortices.

The present experiments showed that there is a cortico-thalamo-cortical projection system in the cat, which originates from the primary visual cortex, relayed by the lateral part of the lateral posterior nucleus of the thalamus, and reaching the medial bank of the lateral suprasylvian visual area. This finding suggests that the thalamus can play a role in transmission of cortical signals from one cortical area to another.

Animals↗

Noradrenergic modulation of cat area 17 neuronal responses to moving visual stimuli.

Orientation and velocity tuning curves were obtained from neurons in cat primary visual cortex before, during and after the iontophoretic application of norepinephrine (NE). While no consistent effects on orientation tuning were observed, the most consistently observed effect of NE on velocity tuning was enhancement of the selectivity for stimulus speed and direction. This was evidenced by a narrowing of velocity tuning curves in 16/28 of the neurons we encountered as well as by an increase in the measured direction index for 13/28 cells. In contrast to NE, acetylcholine and gamma-amino-n-butyric acid (GABA) simply increased and decreased, respectively, the visually-evoked discharges, and in no case altered the shape of the velocity tuning curve. These data suggest that the spatiotemporal tuning of visual cortical neurons may be dependent not only on local interactions between visual afferents and target neurons, but in addition, depend on the activation state of the noradrenergic coeruleo-cortical projection system.

Animals↗

Regional brain glucose metabolism after acute alpha 2-blockade by idazoxan.

BACKGROUND: Several classes of antidepressant drugs act on alpha 2-adrenergic receptors. Studies of patients with disorders responsive to treatment with these drugs report group differences in ex vivo measures of alpha 2-binding and in vivo responses mediated by alpha 2-receptors. Measurement of regional brain metabolic response to an alpha 2-antagonist may be a useful method for further definition of the role alpha 2-receptor regulation plays in the treatment of neuropsychiatric disorders. METHODS: Regional brain glucose metabolism was measured before and after infusion with 200 micrograms/kg idazoxan with use of 18F-fluoro-2-deoxyglucose positron emission tomography in 13 healthy men. Arterial drug concentration, behavioral responses, and cardiovascular responses were also measured. RESULTS: The absolute and normalized glucose metabolic rate significantly increased in primary visual cortex. Significant increases and decreases occurred in normalized metabolic rates in prefrontal cortical regions. Measurement of metabolic effects occurred during the peak cardiovascular response. CONCLUSIONS: Our findings are consistent with regionally specific effects of alpha 2-blockade. This method may be useful for the study of alpha 2-receptor function in humans.

Adrenergic alpha-Antagonists↗

Scalp response topography to dynamic random dot stereograms.

Responses were recorded to dynamic random dot stereograms from 32 sites (acquired in separate 8-channel montages). The disparate stimulus comprised a central, 3 degrees square of 30 arc min crossed disparity, superimposed on a 10.7 degrees square background field. Stimulus onset occurred 100 msec into a 500 msec recording epoch, with a 100 msec stimulus duration. Wave forms for 8 subjects were normalised across the 100 msec pre-stimulus period. Average amplitudes were calculated for the post-onset intervals: 120-140, 140-180, 180-220, 220-260 and 260-300 msec. Contour lines of evoked response amplitude were plotted from these data. These plots are compared with theoretical plots generated from a '3 concentric sphere' model of the head. The results lend support to the proposal that preliminary stereoscopic processing takes place in the primary visual cortex, followed by secondary processing in more anterior cortical regions.

Adult↗