Visual cortex neurons phase-lock selectively to subsets of LFP oscillations.

It is generally thought that apart from receptive field differences, such as preferred orientation and spatial frequency selectivity, primary visual cortex neurons are functionally similar to each other. However, the genetic diversity of cortical neurons plus the existence of inputs additional to those required to explain known receptive field properties might suggest otherwise. Here we report the existence of desynchronized states in anesthetized cat area 17 lasting up to 45 min, characterized by variable narrow-band local field potential (LFP) oscillations in the range 2-100 Hz and the absence of a synchronized 1/f frequency spectrum. During these periods, spontaneously active neurons phase-locked to variable subsets of LFP oscillations. Individual neurons often ignored frequencies that others phase-locked to. We suggest that these desynchronized periods may correspond to REM sleep-like episodes occurring under anesthesia. Frequency-selective codes may be used for signaling during these periods. Hence frequency-selective combination and frequency-labeled pathways may represent a previously unsuspected dimension of cortical organization. NEW & NOTEWORTHY We investigated spontaneous neuronal firing during periods of desynchronized local field potential (LFP) activity, resembling REM sleep, in anesthetized cats. During these periods, neurons synchronized their spikes to specific phases of multiple LFP frequency components, with some neurons ignoring frequencies that others were synchronized to. Some neurons fired at phase alignments of frequency pairs, thereby acting as phase coincidence detectors. These results suggest that internal brain signaling may use frequency combination codes to generate temporally structured spike trains.

Visual cortex maps are optimized for uniform coverage.

Cat visual cortex contains a topographic map of visual space, plus superimposed, spatially periodic maps of ocular dominance, spatial frequency and orientation. It is hypothesized that the layout of these maps is determined by two constraints: continuity or smooth mapping of stimulus properties across the cortical surface, and coverage uniformity or uniform representation of combinations of map features over visual space. Here we use a quantitative measure of coverage uniformity (c') to test the hypothesis that cortical maps are optimized for coverage. When we perturbed the spatial relationships between ocular dominance, spatial frequency and orientation maps obtained in single regions of cortex, we found that cortical maps are at a local minimum for c'. This suggests that coverage optimization is an important organizing principle governing cortical map development.

Visual cortex: a cat's-eye view of the visual system.

Optical imaging data show that the cat's visual cortex contains patches of cells that respond to low spatial and high temporal frequencies; outside the patches, cells respond to high spatial and low temporal frequencies. The results suggest a possible anatomical substrate for psychophysically defined spatial frequency channels.

Cortical organization: modules, polymaps and mosaics.

Recent studies of functional maps in the mammalian visual cortex fail to support the widespread belief that the cortex contains millimetre-sized modules; instead, they reveal a more fluid arrangement in which several separate maps are superimposed, with relatively weak geometric linkages and no common modular subunit.

Is the cerebral cortex modular?

Two types of modular subunit, differing in size, have been hypothesized to exist in the cerebral cortex. The first, known as a mini-column, consists of a group of 110 +/- 10 cells which form a fascicle about 30 micrograms in diameter oriented perpendicular to the cortical surface. Mini-columns are believed to be organized into larger modular groupings, referred to here as macro-columns, with a diameter of about a millimetre or less. Nicholas Swindale argues in this article that there is very little real evidence in favour of either type of module. As an alternative, he suggests that the diversity of types of columnar organization, both within and between different cortical areas, may reflect the diversity of types of information stored in the cortex. Consequently, columnar organization can be expected to vary within and between species, and even between different individuals of the same species. This new interpretation is in line with current neural network theories, which do not demand the existence of structural modularity, but show how complex forms of organization can result from the existence of simple processing rules between the elements of a structure given complex structured inputs.

Role of visual experience in promoting segregation of eye dominance patches in the visual cortex of the cat.

Transneuronal autoradiography was used to study the role of visual experience in the development of ocular dominance patches in the cat. In order to assess quantitatively the effects of visual deprivation, image analysis was used to measure the profiles of grain density in layer IV. Fourier power spectra of these profiles were computed to give a measure of the amplitudes and frequencies of the fluctuations in grain density that were present. Deprivation of normal patterned vision by binocular lid suture or by rearing in total darkness from shortly after birth abolished the dominant periodicity (of about 1.1 mm) in the distribution of left and right eye afferents in layer IV of area 17. A dominant periodicity of about 2.2 mm was, however, present in area 18 of both normal and dark-reared animals. Visual deprivation was not able to reverse segregation. One animal reared normally for 6 weeks was placed in the dark for a further 28 weeks and showed normal periodicities in the distribution of geniculate inputs to area 17. Another animal given 128 hours of experience and kept in the dark for the rest of the time until it was 12 weeks old also showed normal segregation. To determine the minimum amount of visual experience necessary for segregation to occur, four animals were given 8-, 24-, 48-, and 128-hour periods of visual experience and were studied at 12 weeks of age. Eight hours of experience had no detectable effect on segregation; periodicities of intermediate amplitude were present in animals that received 24 and 48 hours of experience, while 128 hours of experience resulted in periodicities of normal amplitude. Recovery from visual deprivation was studied by rearing kittens from birth in the dark for varying periods and then returning them to the normally lit colony room for periods of 6 to 22 weeks. Recovery from 6 weeks of dark rearing was found to be complete; much less recovery occurred following periods of 8 to 25 weeks of initial deprivation, and no recovery at all occurred after 30 weeks of deprivation. It is concluded that the spontaneous activity present in the geniculocortical afferents of dark-reared and lid-sutured cats is not adequate to drive normal periodic segregation in area 17, though it can do so in area 18. Between 48 and 128 hours of visual experience, given before 8 weeks of age, appears to be necessary and sufficient for normal periodic segregation of geniculate afferents in area 17 of the cat.

Automated analysis of normal and glaucomatous optic nerve head topography images.

PURPOSE: To classify images of optic nerve head (ONH) topography obtained by scanning laser ophthalmoscopy as normal or glaucomatous without prior manual outlining of the optic disc. METHODS: The shape of the ONH was modeled by a smooth two-dimensional surface with a shape described by 10 free parameters. Parameters were adjusted by least-squares fitting to give the best fit of the model to the image. These parameters, plus others derived from the image using the model as a basis, were used to discriminate between normal and abnormal images. The method was tested by applying it to ONH topography images, obtained with the Heidelberg Retina Tomograph, from 100 normal volunteers and 100 patients with glaucomatous visual field damage. RESULTS: Many of the parameters derived from the fits differed significantly between normal and glaucomatous ONH images. They included the degree of surface curvature of the disc region surrounding the cup, the steepness of the cup walls, the goodness-of-fit of the model to the image in the cup region, and measures of cup width and cup depth. The statistics of the parameters were analyzed and were used to construct a classifier that gave the probability, P(G), that each image came from the glaucoma population. Images were classified as abnormal if P(G) > 0.5. The probabilities assigned to each image were in most cases close to 0 (normal) or 1 (abnormal). Eighty-seven percent of the sample was confidently classified with P(G) < 0.3 or P(G) > 0.7. Within this group, the overall classification accuracy was 92%. The overall accuracy of the method (the mean of sensitivity and specificity, which were similar) in the whole sample was 89%. CONCLUSIONS: ONH images can be classified objectively and dependably by an automated procedure that does not require prior manual outlining of disc boundaries.

Comparison of psychophysical and electrophysiological testing in early glaucoma.

PURPOSE: To compare the sensitivity and specificity of a wide range of psychophysical and electrophysiological tests in the detection of early glaucomatous damage. METHODS: Forty-three normals and 43 patients with early glaucoma, some still without field defects, were tested with differential light threshold perimetry, short-wavelength automated perimetry, high-pass resolution perimetry, motion detection, flicker contrast sensitivity, flickering and isoluminantly matched letter tests, and pattern and flash electroretinography, including photopic, scotopic, oscillatory potentials, and 30 Hz flicker. Receiver operating characteristic analysis was applied to continuous variables derived from each of the tests. RESULTS: Most parameters reflected glaucomatous loss to some degree, even though only single variables were analyzed separately in the receiver operating characteristic analysis. The pattern electroretinogram and some of the letter acuity tests had the best sensitivity and specificity, followed by short-wavelength automated perimetry and high-pass resolution-perimetry. Motion detection, flicker contrast, and flash electroretinogram parameters scored poorly. Six patients with normal results on the Humphrey field test had abnormal results on many of the other tests. CONCLUSIONS: Applying different psychophysical and electrophysiological tests may add to our ability to detect early glaucomatous damage.

Physiological segregation of geniculo-cortical afferents in the visual cortex of dark-reared cats.

Transneuronal autoradiography in cats dark-reared from birth shows that geniculate terminals from left and right eyes are spread throughout layer IV in area 17 of the visual cortex. In area 18 however, segregation into alternating left and right eye ocular dominance patches appears to be normal. We attempted to correlate this difference between the two areas with the ocular dominance distribution of physiological activity of the geniculate afferents. To do this, microelectrode recordings of multi-unit activity, believed to represent the activity of a number of geniculate terminal axons in the vicinity of the electrode tip, were made in layer IV of areas 17 and 18 in dark-reared cats. The ocular dominance distribution of this activity was predominantly monocular in area 18, as the anatomical results predicted, but surprisingly there were also many regions in area 17 where activity could only be elicited by stimulation of one eye. This has to be reconciled with the anatomical results showing that inputs from both eyes are present throughout layer IV in area 17 of dark-reared cats. Reasons for the discrepancy are discussed.

Vernier acuity for edges defined by flicker.

We investigated the effects of contrast and temporal frequency on vernier edge alignment thresholds. Edges were defined by the presence of a 180 deg phase difference in the temporal modulation waveform of adjacent rectangles with spatially uniform luminances. Thresholds of 10 arc sec or less could be obtained at high contrasts, and flicker rates up to 8 Hz. Above this range, thresholds increased rapidly with decreasing contrast and increasing rates of flicker. Thresholds also increased with increasing temporal frequency over the range 0-20 Hz for contrasts normalized to thresholds for the detection of either flicker or the edge. Linear regression on log-log plots of threshold vs contrast at different temporal frequencies showed that the relationship between threshold and contrast was well described by a power law with an exponent of about -0.5 at temporal frequencies of 8 Hz or lower. About 8 Hz the slope more than doubled and thresholds increased. Thresholds also increased when the relative phase (i.e. the instantaneous sign of the contrast) of the upper and lower edges was reversed, and this effect was observed at all temporal frequencies. Measurements of threshold as a function of the size of a gap between the upper and lower edges suggested that the integration region was larger at 16 Hz or above than at 8 Hz. The results suggest that the channels which mediate vernier hyperacuity are phase sensitive and attenuate frequencies higher than 8 Hz.

Sector-based analysis of optic nerve head shape parameters and visual field indices in healthy and glaucomatous eyes.

PURPOSE: To evaluate the correlations between the sector optic nerve head parameters measured by Heidelberg Retina Tomograph (HRT, Heidelberg Engineering, Heidelberg, Germany), version 1.11S, and the visual field. METHODS: One eye was randomly chosen from 55 individuals with glaucoma and 50 healthy individuals. Each participant had at last one Humphrey visual field, program 30-2 (Humphrey Instruments, San Leandro, CA, U.S.A.), and three 10 degrees HRT pictures. From the mean of the three HRT pictures, global measurements, superior (45 degrees-135 degrees), nasal (135 degrees-225 degrees), inferior (225 degrees-315 degrees), and temporal (315 degrees-45 degrees) sector measurements were calculated for the following parameters: disc area, effective area, area below reference, mean height of contour, volume below surface, volume above surface, volume below reference, volume above reference, and third moment. From the visual field results, mean deviation (MD), superior MD, and inferior MD were calculated. For each HRT parameter we calculated the "r" Pearson correlation with the corresponding visual field measures. RESULTS: Within the combined healthy and glaucomatous groups we found highly significant (p < 0.001) correlations between the following HRT parameters and the visual field MD: inferior and mean high of contour (r = -0.53), inferior and third moment (r = -0.52), global and third moment (r = -0.49), inferior and volume above reference (r = 0.47), superior and third moment (r = -0.46), and superior and area below reference (r = -0.44). Correlations between global mean deviation and nasal or temporal sector parameters were generally smaller and less significant. CONCLUSIONS: Inferior and superior HRT sector parameters were correlated with the respective visual field indices. In many cases these correlations were as strong or stronger than with the global equivalent shape measures.

Vernier thresholds and alignment bias in control, suspect, and glaucomatous eyes.

Detection of vernier offsets requires integration of spatial information from many retinal receptive fields. It was postulated that diminution of the number of ganglion cells in glaucoma may diminish the spatial sampling grain, compromise these integrative processes, and raise vernier thresholds. To test this hypothesis, vernier thresholds were measured in 45 patients with primary open-angle glaucoma (POAG), 45 age-matched glaucoma suspects, and 45 age-matched controls. Alignment bias was measured in 43 subjects from each diagnostic group. Measurements were also obtained in an additional 29 control subjects to evaluate the effect of age on vernier thresholds. All subjects had acuities of 6/7.5 or better. Vernier thresholds were significantly greater in glaucomatous eyes and suspect eyes than in control eyes (p = 0.0002). Mean thresholds were increased by 64% in glaucomatous eyes and 47% in suspect eyes; however, there was significant overlap between the groups. A subgroup of 15 eyes with early glaucomatous damage without localized visual field defects also had vernier thresholds significantly greater than control eyes (p = 0.02). The variances of the alignment biases were significantly greater in the glaucomatous and suspect eyes than in controls eyes (p < 0.05). Our results demonstrate that significant deficits of vernier detection can be demonstrated in some glaucomatous eyes, even in the absence of defects on automated perimetry. Because of the overlap between diagnostic groups, measurement of vernier thresholds cannot be used to distinguish POAG from controls. However, elevation of vernier thresholds may serve as a marker for the early diffuse central dysfunction that occurs in some eyes with glaucoma. The significance of these findings in terms of the mechanisms of glaucomatous damage is discussed.

Contrast sensitivity for flickering and static letters and visual acuity at isoluminance in glaucoma.

PURPOSE: Psychophysical testing was used to assess the effects of early glaucomatous damage on visual functions mediated by the magnocellular and parvocellular pathways. METHODS: We studied 57 eyes with early glaucoma, 92 eyes suspect for glaucoma, and 88 normal eyes. Tests were designed to target the functions of the magnocellular (M) or the parvocellular (P) pathways, and included measurements of contrast sensitivity for letter recognition, using both static presentation, and counterphase modulation at 25 Hz. We assumed that ability to perform the latter task would depend on the integrity of the M-cell pathway. To evaluate P-cell function we measured spatial acuity for a green letter presented against an isoluminant white background. Tests were carried out in the fovea, and at 3 degrees nasal, superior, temporal and inferior to the fovea. RESULTS: Glaucomatous eyes showed, on average, defects in almost all of the functions tested. Threshold elevations for static and isoluminant presentations were generally as large as those for flickering stimuli. The inferior paracentral part of the retina was generally more severely affected than the other locations tested. The defects observed in the suspect population were similar to, although smaller in magnitude than, those found in eyes with glaucoma. A discriminant analysis identified a subset of five tests, including P as well as M pathway tests, which was able to correctly classify 89% of normal and 79% of glaucomatous eyes. CONCLUSIONS: Putative M- and P-cell functions are both impaired at a relatively early stage of glaucoma. Deficits for both types of test are most severe in the inferior paracentral area of the retina (superior visual fields). Psychophysically based detection of the condition can benefit if results from different tests, done at different retinal locations, are combined.

Ability of the heidelberg retina tomograph to detect early glaucomatous visual field loss.

PURPOSE: The Heidleberg Retina Tomograph provides rapid, reproducible measurements of optic disc topography as well as calculations of disc parameters. We used a stepwise discriminant analysis to determine which parameters were most useful in detecting individuals with early glaucomatous visual field loss. METHODS: We studied one eye in each of 45 normal individuals and one eye in each of 46 individuals with early glaucomatous visual field loss. The appearance of the optic disc was not used for classification purposes so as not to bias the diagnostic determination obtained by the instrument. The data were analyzed using the reference plane of the software version 1.10 and using a method incorporating the height of the papillomacular bundle as reference level with and without age correction. RESULTS: We obtained an 89% sensitivity and 78% specificity for the detection of early visual field loss using the standard reference level. The jackknife classification revealed lower sensitivity of 87% and an unchanged specificity of 78%. With the method incorporating the height of the papillomacular bundle as reference level, the sensitivity was 87% and the specificity was 84% for detecting early visual field loss. The jackknife classification revealed a sensitivity of 87% and a specificity of 82%. With the age correction, the sensitivity was 87%, specificity 84% with regular and jackknife classification. With the standard reference level, the important parameters were the third moment and the maximum depth, with the papillomacular bundle reference level volume above reference level added as important, and with age correction, height variation in contour replaced maximum depth in the analysis. CONCLUSION: Three significant shape parameters of the optic disc can be used to detect early glaucomatous visual field loss.

ROC analysis of Heidelberg Retina Tomograph optic disc shape measures in glaucoma.

OBJECTIVE: To determine the capacity of the Heidelberg Retina Tomograph (HRT) optic disc shape measures to detect glaucomatous damage. DESIGN: Prospective study. SETTING: Department of ophthalmology at a university-affiliated hospital in Vancouver. PATIENTS: Ninety-seven consecutive patients from the glaucoma centre and 129 healthy subjects selected from volunteers and employees of the department. One eye of each subject was chosen randomly. OUTCOME MEASURES: Visual fields, as assessed with the Humphrey perimeter, program 30-2, and 12 HRT shape characteristics: disc area, cup area cup/disc area ratio, rim area, cup volume, rim volume, mean cup depth, maximum cup depth, cup shape measure, height variation contour, mean retinal nerve fibre layer thickness and retinal nerve fiber layer cross-section area. ROC (receiver operating characteristic) curves were used to analyse the capacity of each HRT characteristic to detect glaucoma. RESULTS: Statistically significant difference were found between the control and glaucoma groups in age, cup area, cup/disc ratio, rim area, cup volume, rim volume, mean cup depth, cup shape measure, mean retinal nerve fibre layer thickness and retinal nerve fibre layer cross-section area (p < or = 0.003, t-test). The largest (i.e., best) ROC curve area was found for cup shape measure (area = 0.812), rim area (0.809), cup/disc area ratio (0.804) and rim volume (0.768). The mean reference height was 0.31 mm (standard deviation [SD] 0.14 mm) for the control group and 0.29 mm (SD 0.12 mm) for the glaucoma group, a nonsignificant difference. CONCLUSIONS: Cup shape measure was the most predictive HRT shape characteristic.