A weighted and directed interareal connectivity matrix for macaque cerebral cortex.

Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation <1 log unit, range 5 log units). The connectivity profile for each area conformed to a lognormal distribution, where a majority of projections are moderate or weak in strength. In the G29 × 29 interareal subgraph, two-thirds of the connections that can exist do exist. Analysis of the smallest set of areas that collects links from all 91 nodes of the G29 × 91 subgraph (dominating set analysis) confirms the dense (66%) structure of the cortical matrix. The G29 × 29 subgraph suggests an unexpectedly high incidence of unidirectional links. The directed and weighted G29 × 91 connectivity matrix for the macaque will be valuable for comparison with connectivity analyses in other species, including humans. It will also inform future modeling studies that explore the regularities of cortical networks.

Weight consistency specifies regularities of macaque cortical networks.

To what extent cortical pathways show significant weight differences and whether these differences are consistent across animals (thereby comprising robust connectivity profiles) is an important and unresolved neuroanatomical issue. Here we report a quantitative retrograde tracer analysis in the cynomolgus macaque monkey of the weight consistency of the afferents of cortical areas across brains via calculation of a weight index (fraction of labeled neurons, FLN). Injection in 8 cortical areas (3 occipital plus 5 in the other lobes) revealed a consistent pattern: small subcortical input (1.3% cumulative FLN), high local intrinsic connectivity (80% FLN), high-input form neighboring areas (15% cumulative FLN), and weak long-range corticocortical connectivity (3% cumulative FLN). Corticocortical FLN values of projections to areas V1, V2, and V4 showed heavy-tailed, lognormal distributions spanning 5 orders of magnitude that were consistent, demonstrating significant connectivity profiles. These results indicate that 1) connection weight heterogeneity plays an important role in determining cortical network specificity, 2) high investment in local projections highlights the importance of local processing, and 3) transmission of information across multiple hierarchy levels mainly involves pathways having low FLN values.

Laminar distribution of neurons in extrastriate areas projecting to visual areas V1 and V4 correlates with the hierarchical rank and indicates the operation of a distance rule.

The directionality of corticocortical projections is classified as feedforward (going from a lower to higher hierarchical levels), feedback (interconnecting descending levels), and lateral (interconnecting equivalent levels). Directionality is determined by the combined criteria of the laminar patterns of the axon terminals as well as the cells of origins and has been used to construct models of the visual system, which reveals a strict hierarchical organization (Felleman and Van Essen, 1991; Hilgetag et al., 1996a). However, these models are indeterminate partly because we have no indication of the distance separating adjacent levels. Here we have attempted to determine a graded parameter describing the anatomical relationship of interconnected areas. We have investigated whether the precise percentage of labeled supragranular layer neurons (SLN%) in each afferent area after injection in either visual areas V1 or V4 determines its hierarchical position in the model. This shows that pathway directionality in the Felleman and Van Essen model is characterized by a range of SLN% values. The one exception is the projection of the frontal eye field to area V4, which resembles a feedforward projection. Individual areal differences in SLN% values are highly significant, and the number of hierarchical steps separating a target area from a source area is found to be tightly correlated to SLN%. The present results show that the hierarchical rank of each afferent area is reliably indicated by SLN%, and therefore this constitutes a graded parameter that is related to hierarchical distance.

Direct localization by cryo-electron microscopy of secondary structural elements in Escherichia coli 23 S rRNA which differ from the corresponding regions in Haloarcula marismortui.

Insertions were introduced by a two-step mutagenesis procedure into each of five double-helical regions of Escherichia coli 23 S rRNA, so as to extend the helix concerned by 17 bp. The helices chosen were at sites within the 23 S molecule (h9, h25, h45, h63 and h98) where significant length variations between different species are known to occur. At each of these positions, with the exception of h45, there are also significant differences between the 23 S rRNAs of E. coli and Haloarcula marismortui. Plasmids carrying the insertions were introduced into an E. coli strain lacking all seven rrn operons. In four of the five cases the cells were viable and 50 S subunits could be isolated; only the insertion in h63 was lethal. The modified subunits were examined by cryo-electron microscopy (cryo-EM), with a view to locating extra electron density corresponding to the insertion elements. The results were compared both with the recently determined atomic structure of H. marismortui 23 S rRNA in the 50 S subunit, and with previous 23 S rRNA modelling studies based on cryo-EM reconstructions of E. coli ribosomes. The insertion element in h45 was located by cryo-EM at a position corresponding precisely to that of the equivalent helix in H. marismortui. The insertion in h98 (which is entirely absent in H. marismortui) was similarly located at a position corresponding precisely to that predicted from the E. coli modelling studies. In the region of h9, the difference between the E. coli and H. marismortui secondary structures is ambiguous, and the extra electron density corresponding to the insertion was seen at a location intermediate between the position of the nearest helix in the atomic structure and that in the modelled structure. In the case of h25 (which is about 50 nucleotides longer in H. marismortui), no clear extra cryo-EM density corresponding to the insertion could be observed.

On quantifying the bipolarity and axis of the Farnsworth-Munsell 100-Hue test.

A simple method is introduced for analyzing error score distributions from the Farnsworth-Munsell 100-Hue test. The method involves fitting a sine wave directly to the error distribution, and produces estimates of three parameters that characterize the severity of the defect, the degree of bipolarity, and the orientation of the axis of bipolarity, if one is present. The method produces good estimates of the orientation of the axes for congenital defects. It is also amenable to statistical analysis.

Testing the indeterminacy of linear color mechanisms from color discrimination data.

It have previously been reported that, for some choices of the fixed spatial and temporal characteristics of test stimuli, it was possible to estimate the spectral sensitivities of chromatic mechanisms from chromatic discrimination data alone. If mechanism sensitivities could be reliably estimated for any choice of test stimuli characteristics, the influence of spatial and temporal factors on chromatic discrimination performance could be directly measured. Previous studies, using test stimuli with other spatio-temporal characteristics, have found equi-discrimination contours whose ellipsoidal shapes seem to preclude estimation of mechanisms. Since there is no commonly-accepted method for testing the adequacy of ellipsoidal fits of chromatic equi-discrimination contours, it is possible that alternative psychophysical procedures combined with more powerful statistical tests could detect the pattern of deviations from ellipticality reported previously. In this paper, we described psychophysical tests and statistical analyses that, taken together, provide a more powerful test of the indeterminacy of mechanisms than previous methods. We develop a method based on analysis of residuals for detecting the pattern of deviations from ellipticality. We apply these tests under fixed experimental conditions similar to those in which other researchers have found ellipsoidal equi-discrimination contours. For these conditions, for any of the tests performed, we do not reject the hypothesis that equi-discrimination surfaces are ellipsoidal.

Spectral bandwidths for the detection of color.

The spectral properties of human color detection mechanisms were measured using a noise masking technique that minimizes the possibility of off-axis looking and artifactually narrow estimates of bandwidth. Observers were induced to use a single detection mechanism throughout a spectral bandwidth measurement by using sectored noise to mask a time-varying signal of fixed chromatic properties. Sectored noise draws samples from sectors of variable width in the color plane, centered on the signal axis. Contrast thresholds for equiluminant signals that appeared yellow, orange, red and violet were found to depend on the power of the noise, projected along the chromatic axis of the signal, but not on the sector width of the noise. These results are consistent with the activity of spectrally broadband, linear detection mechanisms that are tuned to the signal color directions tested.

Variation of chromatic sensitivity across the life span.

Thresholds were measured along three directions in color space for detecting an equiluminant color change of a set of bars embedded in a larger field of spatio-temporal achromatic noise for observers ranging in age from 3 months to 86 years. Pre-verbal observers were assessed with a forced-choice preferential-looking technique while older observers responded orally or manually. Over the life span, thresholds could be described along each color axis tested by a curve with two trends. Thresholds decreased with each doubling of age by nearly a factor of two until adolescence. Thereafter, thresholds increased by a factor of 1.4-2 with each doubling of age. Sensitivity to chromatic differences varied similarly along all three axes tested, suggesting uniformity in the sensitivity of chromatic mechanisms across the life span.

M- and L-cones in early infancy: I. VEP responses to receptor-isolating stimuli at 4- and 8-weeks of age.

A silent-substitution technique combined with measures of the visually-evoked potential (VEP) was used to determine whether M- and L-cones are functional in early infancy. Data were successfully collected from twenty six infants in response to three receptor-isolation conditions (rod, M- and L-cone isolation) and a luminance-modulation condition. The efficacy of the receptor-isolation conditions was first verified by measuring VEP responses from both dichromatic and color-normal adults to each of the receptor-isolation conditions. Both 4- and 8-week-old infants demonstrated VEP responses to the M- and L-cone isolating stimuli, though the amplitude of the the responses at 4-weeks were reduced compared to those at 8-weeks. These data suggest that the functioning of M- and L-cones can be differentiated as early as 4-weeks of age.

M- and L-cones in early infancy: II. Action spectra at 8 weeks of age.

Field sensitivities were measured under conditions of M- and L-cone isolation for seven infants (8-12 weeks-old) and two adults, using silent-substitution and the visually evoked potential (VEP). The efficacy of the receptor-isolation conditions were first verified by measuring psychophysical and VEP-derived action spectra from two color-normal adults under conditions of M- and L-cone isolation. M- and L-cone action spectra obtained from the two methods were found to be similar to the Smith and Pokorny M- and L-cone fundamentals, respectively. The VEP-derived action spectra obtained from infants and adults were well fit by the Smith and Pokorny M- and L-cone fundamentals. These data, in conjunction with our previous study, confirm that M- and L-cones are operating by 8 weeks and possibly as early as 4 weeks of age.

Detection and identification of mirror-image letter pairs in central and peripheral vision.

Reading performance is poorer in the peripheral than in the central visual field, even after size-scaling to compensate for differences in visual acuity at the different eccentricities. Since several studies have indicated that the peripheral retina is deficient with respect to spatial phase discrimination, we compared the psychometric functions for detection (D) and identification (I) of size-scaled, mirror-symmetric letters (i.e. letters differing in the phase spectra of their odd symmetric components) at three inferior field eccentricities (0, 4, and 7.5 deg) using a two-alternative, temporal, forced-choice procedure and retinal image stabilization to control retinal locus. Each subject's data were fit with Weibull functions and tested for goodness-of-fit under several hypotheses. This analysis revealed that while the psychometric functions were of constant shape across eccentricity for the respective tasks, they showed statistically significant variations in the D/I threshold ratios. However, these variations were so small that poorer reading outside the fovea is unlikely to be due to reduced letter discriminability that might occur secondary to a loss of peripheral field phase sensitivity.

A retinal smear technique for varying grating contrast.

We present here a technique for modulating contrast in gratings seen in Maxwellian-view or on a projection screen. The method can be used with achromatic or chromatic grating stimuli. It is based on a high frequency oscillatory displacement of the grating image, which in turn produces a smearing of the image on the observer's retina. The waveform of the displacement and its amplitude determine the appearance and contrast of the image produced on the retina.

Dependence of color on context in a case of cortical color vision deficiency.

Color constancy depends on sensitivity to change in both illumination spectral properties and object position. We investigated this latter form of color constancy by asking a cerebral achromatopsic to name the colors of papers that were presented atop black, gray or white backgrounds under identical illumination. Comparison of color names across background conditions reveals poor constancy, characterized by a contrasting of foreground and background values that is not corrected by proper anchoring.

M- and L-cones in early infancy: III. Comparison of genotypic and phenotypic markers of color vision in infants and adults.

Genetic analyses were performed on five male children (approximately 3 years), two suspect color-normals and three suspects for congenital color vision deficiencies. These classifications were based on visually-evoked potential (VEP) responses to M- and L-cone-isolating stimuli obtained in a previous study when each subject was either 4- or 8-weeks old. The present analyses were performed in a blind study to characterize the genotypes of these subjects. Four male adults with various color vision phenotypes were also tested as a control. DNA was isolated using a non-invasive technique followed by polymerase chain reaction (PCR) amplification and restriction enzyme analysis to examine the genomic DNA of each subject. The genetic analyses confirmed the VEP identification of two color defective infants, and were consistent with the diagnosis of two other infants as color normal. A third infant was predicted by VEP analysis to have a protan defect, but he did not have a gene array typically found in protan observers.

Theory of wavelength discrimination in tritanopia.

Many theories of color discrimination predict a discontinuity in the wavelength-discrimination function of a tritanope at the point in the spectrum at which the rate of change of the visual signal constrained to an equiluminant plane passes through zero (near 460 nm). The predicted discontinuity follows from the use of a first-order approximation for which the reciprocal of the slope of the response function that generates the visual signal is proportional to the discrimination limen. In view of the good discrimination shown by such observers elsewhere in the spectrum, however, such a singularity is impossible. I show that the inclusion of the higher-order terms produces a finite value in the 460-nm region that falls in the range of values from the literature that have been obtained experimentally.

Reading with fixed and variable character pitch.

We compared the effects of fixed and variable (proportional) spacing on reading speeds and found variable pitch to yield better performance at medium and large character sizes and fixed pitch to be superior for character sizes approaching the acuity limit. The data indicate at least two crowding effects at the smallest sizes: one that interferes with individual character identification and one that interferes with word identification. A control experiment using rapid serial visual presentation suggests that it is the greater horizontal compression and consequently reduced eye-movement requirements of variable pitch that are responsible for its superiority at medium and large character sizes.

Activation of complement by cold agglutinins.

OBJECTIVE: To review recent reports on the interaction of cold agglutinins with the complement system and its relevance to cold agglutinin disease. DATA SOURCES: Review articles and original papers have been selected for this contribution. SELECTION CRITERIA: The report focuses on experimental data available from in vitro studies as well as clinical findings regarding the mechanisms of cold agglutinin-induced complement activation. RESULTS: Despite the observation that only few cold agglutinins (almost exclusively IgM molecules with anti-I specificity) induce in vitro hemolysis of human red blood cells with human serum (homologous system), the vast majority of these autoantibodies are able to initiate the classical pathway sequence with the fixation of C1 and to a lesser degree of C4. The ability of IgM cold agglutinins to activate, in principle, complement is demonstrated by their hemolytic efficiency in the presence of animal serum as a source of heterologous complement. In addition to the thermal amplitude of cold agglutinin binding, a possible interference with membrane regulatory proteins may render certain cold agglutinins hemolytically active in a homologous system. CONCLUSION: Despite a hemolytic inefficiency, cold agglutinin-induced fixation of early complement components up to C3 leads to an accelerated clearance of red cells from the circulation by hepatic sequestration. However, it is not yet clear, to what degree these cells are eliminated by the reticuloendothelial system or whether they return to the circulation. Dependent on the amount of membrane-bound C3 fragments these cells may even be protected against further cold agglutinin-induced complement attack.

Relating cone signals to color appearance: failure of monotonicity in yellow/blue.

Observers performed red-green and yellow-blue hue cancellation tasks for a 0.8-deg circular test field on a dark surround, by manipulating the excitation level of one cone class while the other two classes were held constant. The results of the red-green judgments conformed to classical opponent color theory in that both L- and S-cone excitation levels were antagonistic to M-cone signals. The yellow-blue judgments revealed a nonmonotonic nonlinearity in which the S-cone signal could act either antagonistically or synergistically with M- and L-cone signals. These results demonstrate that fixed hue sensations should not be associated with a given class of cone, even at the level of opponent neural coding.