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.

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.

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 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.

Cognitive development prior to onset of psychosis.

Schizophrenia patients commonly exhibit substantial and diffuse cognitive impairment. Evidence suggests that subtle cognitive deficits are already apparent in childhood and adolescence, many years prior to onset of psychosis. While there is almost unequivocal evidence of some degree of cognitive impairment in individuals who later develop schizophrenia, the literature remains inconclusive regarding the exact nature of this impairment and warrants careful review and interpretation. Meta-analytic findings suggest that individuals who later develop schizophrenia, but not related disorders, such as bipolar disorder, exhibit a premorbid IQ deficit of around 8 points. Several studies have also found evidence for premorbid deficits across most cognitive domains, such as language, processing speed and executive functions. Longitudinal studies, although rare, suggest that individuals who go on to develop schizophrenia may show a course of increasing cognitive impairment prior to onset of psychosis. While evidence regarding the etiology of premorbid deficits is scarce, common and rare genetic variants, as well as environmental factors such as obstetric complications and cannabis use may play an important role and warrant further examination. In this selected review, we give an overview of population-based studies on premorbid cognitive deficits in schizophrenia, with a special focus on evidence regarding the specificity, profile and course of these deficits.

Individual differences in human eye movements: An oculomotor signature?

Human eye movements are stereotyped and repeatable, but how specific to a normal individual are the quantitative properties of his or her eye movements? We recorded saccades, anti-saccades and smooth-pursuit eye movements in a sample of over 1000 healthy young adults. A randomly selected subsample (10%) of participants were re-tested on a second occasion after a median interval of 18.8days, allowing us to estimate reliabilities. Each of several derived measures, including latencies, accuracies, velocities, and left-right asymmetries, proved to be very reliable. We give normative means and distributions for each measure and describe the pattern of correlations amongst them. We identify several measures that exhibit significant sex differences. The profile of our oculomotor measures for an individual constitutes a personal oculomotor signature that distinguishes that individual from most other members of the sample of 1000.

An exploratory factor analysis of visual performance in a large population.

A factor analysis was performed on 25 visual and auditory performance measures from 1060 participants. The results revealed evidence both for a factor relating to general perceptual performance, and for eight independent factors that relate to particular perceptual skills. In an unrotated PCA, the general factor for perceptual performance accounted for 19.9% of the total variance in the 25 performance measures. Following varimax rotation, 8 consistent factors were identified, which appear to relate to (1) sensitivity to medium and high spatial frequencies, (2) auditory perceptual ability (3) oculomotor speed, (4) oculomotor control, (5) contrast sensitivity at low spatial frequencies, (6) stereo acuity, (7) letter recognition, and (8) flicker sensitivity. The results of a hierarchical cluster analysis were consistent with our rotated factor solution. We also report correlations between the eight performance factors and other (non-performance) measures of perception, demographic and anatomical measures, and questionnaire items probing other psychological variables.

General and specific factors in the processing of faces.

The ability to recognize faces varies considerably between individuals, but does performance co-vary for tests of different aspects of face processing? For 397 participants (of whom the majority were university students) we obtained scores on the Mooney Face Test, Glasgow Face Matching Test (GFMT), Cambridge Face Memory Test (CFMT) and Composite Face Test. Overall performance was significantly correlated for each pair of tests, and we suggest the term f for the factor underlying this pattern of positive correlations. However, there were large variations in the amount of variance shared by individual tests: The GFMT and CFMT are strongly related, whereas the GFMT and the Mooney test tap largely independent abilities. We do not replicate a frequently reported relationship between holistic processing (from the Composite test) and face recognition (from the CFMT)-indeed, holistic processing does not correlate with any of our tests. We report associations of performance with digit ratio and autism-spectrum quotient (AQ), and from our genome-wide association study we include a list of suggestive genetic associations with performance on the four face tests, as well as with f.

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.

Early-life metal exposure and schizophrenia: A proof-of-concept study using novel tooth-matrix biomarkers.

BACKGROUND: Despite evidence for the effects of metals on neurodevelopment, the long-term effects on mental health remain unclear due to methodological limitations. Our objective was to determine the feasibility of studying metal exposure during critical neurodevelopmental periods and to explore the association between early-life metal exposure and adult schizophrenia. METHODS: We analyzed childhood-shed teeth from nine individuals with schizophrenia and five healthy controls. We investigated the association between exposure to lead (Pb(2+)), manganese (Mn(2+)), cadmium (Cd(2+)), copper (Cu(2+)), magnesium (Mg(2+)), and zinc (Zn(2+)), and schizophrenia, psychotic experiences, and intelligence quotient (IQ). We reconstructed the dose and timing of early-life metal exposures using laser ablation inductively coupled plasma mass spectrometry. RESULTS: We found higher early-life Pb(2+) exposure among patients with schizophrenia than controls. The differences in log Mn(2+) and log Cu(2+) changed relatively linearly over time to postnatal negative values. There was a positive correlation between early-life Pb(2+) levels and psychotic experiences in adulthood. Moreover, we found a negative correlation between Pb(2+) levels and adult IQ. CONCLUSIONS: In our proof-of-concept study, using tooth-matrix biomarker that provides direct measurement of exposure in the fetus and newborn, we provide support for the role of metal exposure during critical neurodevelopmental periods in psychosis.

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.

Speed and the coherence of superimposed chromatic gratings.

On the basis of measurements of the perceived coherence of superimposed drifting gratings, Krauskopf and Farell (1990) proposed that motion is analysed independently in different chromatic channels. They found that two gratings appeared to slip if each modulated one of the two 'cardinal' color mechanisms S/(L+M) and L/(L+M). If the gratings were defined along intermediate color directions, observers reported a plaid, moving coherently. We hypothesised that slippage might occur in chromatic gratings if the motion signal from the S/(L+M) channel is weak and equivalent to a lower speed. We asked observers to judge coherence in two conditions. In one, S/(L+M) and L/(L+M) gratings were physically the same speed. In the other, the two gratings had perceptually matched speeds. We found that the relative incoherence of cardinal gratings is the same whether gratings are physically or perceptually matched in speed. Thus our hypothesis was firmly contradicted. In a control condition, observers were asked to judge the coherence of stationary gratings. Interestingly, the difference in judged coherence between cardinal and intermediate gratings remained as strong as it was when the gratings moved. Our results suggest a possible alternative interpretation of Krauskopf and Farell's result: the processes of object segregation may precede the analysis of the motion of chromatic gratings, and the same grouping signals may prompt object segregation in the stationary and moving cases.

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.

A population study of binocular function.

As part of a genome-wide association study (GWAS) of perceptual traits in healthy adults, we measured stereo acuity, the duration of alternative percepts in binocular rivalry and the extent of dichoptic masking in 1060 participants. We present the distributions of the measures, the correlations between measures, and their relationships to other psychophysical traits. We report sex differences, and correlations with age, interpupillary distance, eye dominance, phorias, visual acuity and personality. The GWAS, using data from 988 participants, yielded one genetic association that passed a permutation test for significance: The variant rs1022907 in the gene VTI1A was associated with self-reported ability to see autostereograms. We list a number of other suggestive genetic associations (p<10(-5)).

An online version of the Mooney Face Test: phenotypic and genetic associations.

The Mooney Face Test is a widely used test of face perception, but was originally designed to be administered by personal interview. We have developed a three-alternative forced-choice version for online testing. We tested 397 healthy adults between the ages of 18 and 42 (M=24 years). There was a wide range of performance (64-100% correct; M=89.6%). We observed a significant sex difference favoring males (.31 standard deviation; p =.004). In addition, independently of sex, higher 2D:4D digit ratios were significantly associated with higher scores (ρ=.14, p=.006). A genome-wide association study (GWAS) for a subset of 370 participants identified an association between Mooney performance and a polymorphism in the RAPGEF5 gene (rs1522280; p=9.68×10(-8)). This association survives a permutation test (p=.031).

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.

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.