A possible mechanism of neural read-out from a molecular engram.

What is the physical basis of declarative memory? The predominant view holds that stored information is embedded in the structure of a neural net, that is, in the signs and weights of its synaptic connections. An alternative possibility is that storage and processing are separated, and that the engram is encoded chemically, most probably in the sequence of a nucleic acid. One deterrent to adoption of the latter hypothesis has been the difficulty of envisaging how neural actively could be converted to and from a molecular code. Our purpose here is limited to suggesting how a molecular sequence could be read out from nucleic acid to neural activity by means of nanopores.

'The last channel': vision at the temporal margin of the field.

The human visual field, on the temporal side, extends to at least 90° from the line of sight. Using a two-alternative forced-choice procedure in which observers are asked to report the direction of motion of a Gabor patch, and taking precautions to exclude unconscious eye movements in the direction of the stimulus, we show that the limiting eccentricity of image-forming vision can be established with precision. There are large, but reliable, individual differences in the limiting eccentricity. The limiting eccentricity exhibits a dependence on log contrast; but it is not reduced when the modulation visible to the rods is attenuated, a result compatible with the histological evidence that the outermost part of the retina exhibits a high density of cones. Our working hypothesis is that only one type of neural channel is present in the far periphery of the retina, a channel that responds to temporally modulated stimuli of low spatial frequency and that is directionally selective.

Discrimination of hue angle and discrimination of colorimetric purity assessed with a common metric.

It has been suggested that thresholds for discriminating colorimetric purity are systematically higher than those for discriminating hue angle, a difference captured in Judd's phrase "the super-importance of hue." However, to compare the two types of discrimination, the measured thresholds must be expressed in the same units. An attractive test is offered by measurements along the horizontal lines in the chromaticity diagram of MacLeod and Boynton [ J. Opt. Soc. Am.69, 1183 (1979)JOSAAH0030-394110.1364/JOSA.69.001183], i.e., a chromaticity diagram. A horizontal line that extends radially from the white point represents a variation in colorimetric purity alone (and subjectively a variation that is primarily in saturation). In contrast, a horizontal line that runs along the $x$x axis of the diagram, close to the long-wave spectrum locus, corresponds predominantly to variation in hue angle. Yet, in both cases, only the ratio of the excitations of the long- and middle-wave cones is being modulated, and so the thresholds can be expressed in a common metric. Measuring forced-choice thresholds for 180 ms foveal targets presented on a steady field metameric to Illuminant D65, we do not find general support for Judd's working rule that thresholds for purity are systematically twice those for saturation. Thresholds for colorimetric purity were only a little higher than those for hue angle, and the advantage for hue was seen in only part of the ranges that were tested. However, in the upper-left quadrant of the MacLeod-Boynton diagram, where the excitation of short-wave cones is high and where both hue angle and colorimetric purity vary along any given horizontal line, thresholds were indeed sometimes half those observed for discrimination of purity alone.

The Oxytocin Receptor Gene ( OXTR) and Face Recognition.

A recent study has linked individual differences in face recognition to rs237887, a single-nucleotide polymorphism (SNP) of the oxytocin receptor gene ( OXTR; Skuse et al., 2014). In that study, participants were assessed using the Warrington Recognition Memory Test for Faces, but performance on Warrington's test has been shown not to rely purely on face recognition processes. We administered the widely used Cambridge Face Memory Test-a purer test of face recognition-to 370 participants. Performance was not significantly associated with rs237887, with 16 other SNPs of OXTR that we genotyped, or with a further 75 imputed SNPs. We also administered three other tests of face processing (the Mooney Face Test, the Glasgow Face Matching Test, and the Composite Face Test), but performance was never significantly associated with rs237887 or with any of the other genotyped or imputed SNPs, after corrections for multiple testing. In addition, we found no associations between OXTR and Autism-Spectrum Quotient scores.

Superior discrimination for hue than for saturation and an explanation in terms of correlated neural noise.

The precision of human colour discrimination depends on the region of colour space in which measurements are made and on the direction in which the compared colours-the discriminanda-differ. Working in a MacLeod-Boynton chromaticity diagram scaled so that thresholds at the white point were equal for the two axes, we made measurements at reference points lying on lines that passed at 45° or -45° through the white point. At a given reference chromaticity, we measured thresholds either for saturation (i.e. for discriminanda lying radially along the line passing through the white point) or for hue (i.e. for discriminanda lying on a tangent of a circle passing through the reference point and centred on the white point). The discriminanda always straddled the reference point in chromaticity. The attraction of this arrangement is that the two thresholds can be expressed in common units. All that differs between saturation and hue measurements is the phase with which the short-wave signal is combined with the long-/middle-wave signal. Except for chromaticities very close to the white point, saturation thresholds were systematically higher than hue thresholds. We offer a possible explanation in terms of correlated neural noise.

Is discrimination enhanced at a category boundary? The case of unique red.

Is chromatic discrimination enhanced at the boundary between different hues? In previous studies, we gave a positive answer for the case of the locus of unique blues and yellows, the boundary that divides color space into reddish and greenish hues. But we did not find enhancement at the locus of unique green, the boundary between yellowish and bluish hues. In the present study, we examined discrimination near the locus of unique red. In interleaved experimental runs, we obtained (1) discrimination thresholds using a four-alternative spatial forced choice and (2) phenomenological judgments of the locus of unique red. When measurements were made along lines parallel to the locus of unique blues and yellows in a MacLeod-Boynton diagram, the locus of minimal thresholds coincided approximately with the locus of unique red; however, this was not the case when measurements were made along lines orthogonal to the locus of unique blues and yellows. To account for these and earlier results, we suppose that the neural channel that determines the discrimination threshold will sometimes coincide with the channel that determines the perceptual hue equilibrium and sometimes will not. If a given point in chromaticity space is a unique hue, then it is expected to remain a unique hue independently of the direction in which measurements are made; however, discrimination thresholds almost certainly will depend on different underlying channels when measurements are made in different directions through the same point in chromaticity space.

A new Mooney test.

Since its introduction in 1957, the Mooney test has continued to see active use in studies of visual perception, in studies using brain imaging, and in clinical research. Mooney's original version is of limited length, however, and was designed to be administered by time-consuming personal interview. We have developed a new, extended version of the Mooney test that is suitable for online testing and for use in a test-retest paradigm. The Mooney-Verhallen Test (MVT) comprises 144 trials, takes on average less than 10 min to complete, and has a Spearman-Brown-corrected test-retest reliability of ρ = .89. We outline our methods for developing the stimuli and for selecting the final stimulus set, and we present the results from two rounds of testing on two independent samples of 374 participants and 505 participants, respectively. The test is freely available for scientific use.

Is discrimination enhanced at the boundaries of perceptual categories? A negative case.

The human visual system imposes discrete perceptual categories on the continuous input space that is represented by the ratios of excitations of the cones in the retina. Is discrimination enhanced at the boundaries between perceptual hues, in the way that discrimination may be enhanced at the boundaries between speech sounds in hearing? In the chromaticity diagram, the locus of unique green separates colours that appear yellowish from those that appear bluish. Using a two-alternative spatial forced choice and an adapting field equivalent to the Daylight Illuminant D65, we measured chromatic discrimination along lines orthogonal to the locus of unique green. In experimental runs interleaved with these performance measurements, we obtained estimates of the phenomenological boundary from the same observers. No enhancement of objectively measured discrimination was observed at the category boundary between yellowish and bluish hues. Instead, thresholds were minimal at chromaticities where the ratio of long-wave to middle-wave cone excitation was the same as that for the background adapting field.

Symmetries and asymmetries in chromatic discrimination.

Under conditions of adaptation to a steady neutral field (metameric to Daylight Illuminant D65), forced-choice thresholds for color discrimination were measured for brief targets presented to the human fovea. Measurements were made along +45° and -45° lines in a MacLeod-Boynton chromaticity space scaled so that the locus of unique yellow and unique blue lay at -45°. The lines were symmetrical relative to the tritan line passing through the chromaticity of D65. Thresholds increased with distance of the probe chromaticity from D65. Thresholds were higher for saturation discrimination than for hue discrimination. A region of enhanced discrimination was found for thresholds measured orthogonally to the locus of unique blue and unique yellow. There may be an analogous enhancement near the loci of unique red and unique green.

Counterphase modulation flicker photometry: phenotypic and genotypic associations.

The OSCAR test, a clinical device that uses counterphase flicker photometry, is believed to be sensitive to the relative numbers of long-wavelength and middle-wavelength cones in the retina, as well as to individual variations in the spectral positions of the photopigments. As part of a population study of individual variations in perception, we obtained OSCAR settings from 1058 participants. We report the distribution characteristics for this cohort. A randomly selected subset of participants was tested twice at an interval of at least one week: the test-retest reliability (Spearman's rho) was 0.80. In a whole-genome association analysis we found a provisional association with a single nucleotide polymorphism (rs16844995). This marker is close to the gene RXRG, which encodes a nuclear receptor, retinoid X receptor γ. This nuclear receptor is already known to have a role in the differentiation of cones during the development of the eye, and we suggest that polymorphisms in or close to RXRG influence the relative probability with which long-wave and middle-wave opsin genes are expressed in human cones.

Individual differences provide psychophysical evidence for separate on- and off-pathways deriving from short-wave cones.

Distinct neural populations carry signals from short-wave (S) cones. We used individual differences to test whether two types of pathways, those that receive excitatory input (S+) and those that receive inhibitory input (S-), contribute independently to psychophysical performance. We also conducted a genome-wide association study (GWAS) to look for genetic correlates of the individual differences. Our psychophysical test was based on the Cambridge Color Test, but detection thresholds were measured separately for S-cone spatial increments and decrements. Our participants were 1060 healthy adults aged 16-40. Test-retest reliabilities for thresholds were good (ρ=0.64 for S-cone increments, 0.67 for decrements and 0.73 for the average of the two). "Regression scores," isolating variability unique to incremental or decremental sensitivity, were also reliable (ρ=0.53 for increments and ρ=0.51 for decrements). The correlation between incremental and decremental thresholds was ρ=0.65. No genetic markers reached genome-wide significance (p<5×10(-7)). We identified 18 "suggestive" loci (p<10(-5)). The significant test-retest reliabilities show stable individual differences in S-cone sensitivity in a normal adult population. Though a portion of the variance in sensitivity is shared between incremental and decremental sensitivity, over 26% of the variance is stable across individuals, but unique to increments or decrements, suggesting distinct neural substrates. Some of the variability in sensitivity is likely to be genetic. We note that four of the suggestive associations found in the GWAS are with genes that are involved in glucose metabolism or have been associated with diabetes.

Genetic association suggests that SMOC1 mediates between prenatal sex hormones and digit ratio.

Men and women differ statistically in the relative lengths of their index and ring fingers; and the ratio of these lengths has been used as a biomarker for prenatal testosterone. The ratio has been correlated with a wide range of traits and conditions including prostate cancer, obesity, autism, ADHD, and sexual orientation. In a genome-wide association study of 979 healthy adults, we find that digit ratio is strongly associated with variation upstream of SMOC1 (rs4902759: P = 1.41 × 10(-8)) and a meta-analysis of this and an independent study shows a probability of P = 1.5 × 10(-11). The protein encoded by SMOC1 has recently been shown to play a critical role in limb development; its expression in prostate tissue is dependent on sex hormones, and it has been implicated in the sexually dimorphic development of the gonads. We put forward the hypothesis that SMOC1 provides a link between prenatal hormone exposure and digit ratio.

Do different 'magnocellular tasks' probe the same neural substrate?

The sensory abnormalities associated with disorders such as dyslexia, autism and schizophrenia have often been attributed to a generalized deficit in the visual magnocellular-dorsal stream and its auditory homologue. To probe magnocellular function, various psychophysical tasks are often employed that require the processing of rapidly changing stimuli. But is performance on these several tasks supported by a common substrate? To answer this question, we tested a cohort of 1060 individuals on four 'magnocellular tasks': detection of low-spatial-frequency gratings reversing in contrast at a high temporal frequency (so-called frequency-doubled gratings); detection of pulsed low-spatial-frequency gratings on a steady luminance pedestal; detection of coherent motion; and auditory discrimination of temporal order. Although all tasks showed test-retest reliability, only one pair shared more than 4 per cent of variance. Correlations within the set of 'magnocellular tasks' were similar to the correlations between those tasks and a 'non-magnocellular task', and there was little consistency between 'magnocellular deficit' groups comprising individuals with the lowest sensitivity for each task. Our results suggest that different 'magnocellular tasks' reflect different sources of variance, and thus are not general measures of 'magnocellular function'.

Bongard and Smirnov on the tetrachromacy of extra-foveal vision.

In Moscow in the 1950's, the physicist M. M. Bongard developed the use of silent substitution to establish the number of dimensions of human or animal colour vision and to derive colour-matching functions either for whole organisms or for individual neuronal channels. In 1956, he and his colleague M. S. Smirnov reported that extra-foveal human vision was tetrachromatic when tested by the silent-substitution method that they called 'replacement colorimetry'. In the steady state, trichromatic matches were possible in extra-foveal regions, but transients were visible when one such match was replaced by another. If, however, a match was made with four primaries, then a silent substitution was possible; and such matches - unlike trichromatic ones - were stable with light level and with changes in the state of chromatic adaptation. Bongard and Smirnov believed that the fourth receptor had the spectral sensitivity of the rods, but of course they were working long before the discovery of intrinsically photosensitive retinal ganglion cells. On the fiftieth anniversary of Bongard's grievous death, we provide a translation of Bongard and Smirnov's paper on the tetrachromacy of extra-foveal vision. In a commentary, we give the background to their work and provide further details of their apparatus and procedure. We briefly discuss related research and the reception in the West of Bongard and Smirnov's claims. We suggest that an analogy can be made between the tetrachromacy of the parafovea and the 'weak tetrachromacy' of heterozygotes for anomalous colour vision, whose trichromatic matches are not stable with chromatic adaptation.

Parafoveal color discrimination: a chromaticity locus of enhanced discrimination.

Are boundaries between color categories associated with enhanced discrimination? In the present experiments, chromatic thresholds were obtained for discriminations along lines orthogonal to the yellow-blue axis of color space. The targets were parafoveal and thresholds were measured with a spatial two-alternative forced choice. In interleaved experimental runs, we also obtained empirical estimates of the subjective yellow-blue line by asking observers to categorize colors as reddish or greenish. Both types of measurement were made in the presence of a steady background that was metameric to equal-energy white. In a limited region from desaturated yellow to desaturated blue, an enhanced discrimination is found near the subjective transition between reddish and greenish hues. This line of optimal discrimination is not aligned with either of the cardinal axes of color space: In a MacLeod-Boynton chromaticity diagram, it runs obliquely with negative slope.

The dimensionality of color vision in carriers of anomalous trichromacy.

Some 12% of women are carriers of the mild, X-linked forms of color vision deficiencies called "anomalous trichromacy." Owing to random X chromosome inactivation, their retinae must contain four classes of cone rather than the normal three; and it has previously been speculated that these female carriers might be tetrachromatic, capable of discriminating spectral stimuli that are indistinguishable to the normal trichromat. However, the existing evidence is sparse and inconclusive. Here, we address the question using (a) a forced-choice version of the Rayleigh test, (b) a test using multidimensional scaling to reveal directly the dimensionality of the participants' color space, and (c) molecular genetic analyses to estimate the X-linked cone peak sensitivities of a selected sample of strong candidates for tetrachromacy. Our results suggest that most carriers of color anomaly do not exhibit four-dimensional color vision, and so we believe that anomalous trichromacy is unlikely to be maintained by an advantage to the carriers in discriminating colors. However, 1 of 24 obligate carriers of deuteranomaly exhibited tetrachromatic behavior on all our tests; this participant has three well-separated cone photopigments in the long-wave spectral region in addition to her short-wave cone. We assess the likelihood that behavioral tetrachromacy exists in the human population.

How does the human visual system compare the speeds of spatially separated objects?

We measured psychophysical thresholds for discriminating the speeds of two arrays of moving dots. The arrays could be juxtaposed or could be spatially separated by up to 10 degrees of visual angle, eccentricity being held constant. We found that the precision of the judgments varied little with separation. Moreover, the function relating threshold to separation was similar whether the arrays moved in the same, in opposite or in orthogonal directions. And there was no significant difference in threshold whether the two stimuli were initially presented to the same cerebral hemisphere or to opposite ones. How are human observers able to compare stimuli that fall at well separated positions in the visual field? We consider two classes of explanation: (i) Observers' judgments might be based directly on the signals of dedicated 'comparator neurons', i.e. neurons drawing inputs of opposite sign from local regions of the visual field. (ii) Signals about local features might be transmitted to the site of comparison by a shared 'cerebral bus', where the same physical substrate carries different information from moment to moment. The minimal effects of proximity and direction (which might be expected to influence local detectors of relative motion), and the combinatorial explosion in the number of comparator neurons that would be required by (i), lead us to favor models of type (ii).

The chemistry of John Dalton's color blindness.

John Dalton described his own color blindness in 1794. In common with his brother, he confused scarlet with green and pink with blue. Dalton supposed that his vitreous humor was tinted blue, selectively absorbing longer wavelengths. He instructed that his eyes should be examined after his death, but the examination revealed that the humors were perfectly clear. In experiments presented here, DNA extracted from his preserved eye tissue showed that Dalton was a deuteranope, lacking the middlewave photopigment of the retina. This diagnosis is shown to be compatible with the historical record of his phenotype, although it contradicts Thomas Young's belief that Dalton was a protanope.

Adaptive evolution of color vision genes in higher primates.

The intron 4 sequences of the three polymorphic alleles at the X-linked color photo-pigment locus in the squirrel monkey and the marmoset reveal that the alleles in each species are exceptionally divergent. The data further suggest either that each triallelic system has arisen independently in these two New World monkey lineages, or that in each species at least seven deletions and insertions (14 in the two species) in intron 4 have been transferred and homogenized among the alleles by gene conversion or recombination. In either case, the alleles in each species apparently have persisted more than 5 million years and probably have been maintained by overdominant selection.