Variants of TPH2 interact with fast visual processing as assessed by metacontrast.

Sensitivity to threatening or otherwise unpleasant visual stimuli has become a widely used measure of potential vulnerability/resilience. Basically, experiments using this strategy present brief stimuli, often followed by a mask, and individuals' sensitivity is measured. However, it has not been asked whether the individual differences in threat detection or adaptive resilience associated with genetic variability-related endophenotypes might be just a function of some basic visual functions involved in processing and reporting brief visual stimuli without any emotional content. Effects attributed to emotional processing may be confounded by variability in simple basic visual skills. However, if simple visual skills are variable depending on common genetic variability, simple perceptual tests of screening for genetic risks can be developed. In a sample of normal human individuals, we studied the effects of a single nucleotide polymorphism (rs4570625) in the gene that encodes the rate-limiting enzyme in serotonin synthesis, TPH2, on metacontrast masking. Visual discrimination of target shapes that were incongruent with mask shapes was poorer in G homozygotes (typically considered more resilient individuals) compared with T-allele carriers and this effect was influenced by participants' sex. Implications for the development of psychophysical testing-based methods of screening for vulnerability/resilience in relation to the pathology of the serotonergic system-related dysfunction are considered.

Brain dopaminergic system related genetic variability interacts with target/mask timing in metacontrast masking.

Dopaminergic system of the brain is believed to be strongly involved in normal and pathological behavioral phenotypes of attention. In metacontrast masking studies attentional effects on metacontrast are predominantly expressed when time intervals between a target stimulus and a masking stimulus are longer rather than shorter. Taken together, this predicts that variability in common genes known to be involved in dopaminergic function could interact with target/mask intervals in determining the effects of metacontrast masking. We tested this by genotyping participants of the masking experiment for the COMT Val158Met, DAT1 3'UTR 40 bp VNTR, and DRD4 exon 3 48b p VNTR variability. We found that Val homozygotes and subjects with long repeat variants of the DRD4 gene showed relatively higher level of correct target perception with a longer target/mask time interval than with a shorter time interval while DAT1 variability did not have any effects. Implications of this result for the development of psychophysical testing based methods of screening for vulnerability/resilience in relation to the pathology of the dopaminergic systems related attentional dysfunction are considered.

Single 5HTR2A-1438 A/G nucleotide polymorphism affects performance in a metacontrast masking task: implications for vulnerability testing and neuromodulation of pyramidal cells.

It is known that 5HTR2A (rs6311) receptors have high concentration in the cortical layer-5 pyramidal neurons and that these receptors play an important role in the modulation of neurocognitive functions. For example, layer-5 pyramidal neurons mediate cellular level integrative interaction of primary sensory afferent signals and top-down signals exerting contextual modulatory influence. It is also known that genetic variability of 5HTR2A is implicated in individual differences in mental processes. Interestingly, serotonin selectively enhances the asynchronous type of glutamate release when modulating the activity of cortical layer-5 pyramidal neurons, with a post-stimulation delay of this effect at about 50 ms. There are not many behavioral tasks capable of tapping that small temporal intervals in terms of change of the values of independent variables leading to an observable change in the subjects' behavior. However, in the metacontrast masking vision task stimulus onset asynchronies between target and mask critical for the change in the expression of the masking effect correspond to this small temporal value. Thus we hypothesized that genetic variability in 5HTR2A (rs6311) is likely to be associated with different behavioral effects of metacontrast masking and more specifically, that because A allele carriers typically demonstrate greater promoter activity, target-to-mask asynchrony variations should have stronger impact on the masking effect especially with this group of subjects. We obtained support for this hypothesis, but only when target and mask shapes were mutually incongruent.

Can common functional gene variants affect visual discrimination in metacontrast masking?

Mechanisms of visual perception should be robustly fast and provide veridical information about environmental objects in order to facilitate survival and successful coping. Because species-specific brain mechanisms for fast vision must have evolved under heavy pressure for efficiency, it has been held that different human individuals see the physical world in the same way and produce psychophysical functions of visual discrimination that are qualitatively the same. For many years, this assumption has been implicitly accepted in vision research studying extremely fast, basic visual processes, including studies of visual masking. However, in recent studies of metacontrast masking surprisingly robust individual differences in the qualitative aspects of subjects' performance have been found. As the basic species-specific visual functions very likely are based on universal brain mechanisms of vision, these differences probably are the outcome of variability in ontogenetic development (i.e., formation of idiosyncrasic skills of perception). Such developmental differences can be brought about by variants of genes that are differentially expressed in the course of CNS development. The objective of this study was to assess whether visual discrimination in metacontrast masking is related to three widely studied genetic polymorphisms implicated in brain function and used here as independent variables. The findings suggest no main effects of BDNF Val66Met, NRG1/rs6994992, or 5-HTTLPR polymorphisms on metacontrast performance, but several notable interactions of genetic variables with gender, stage of the sequence of experimental trials, perceptual strategies, and target/mask shape congruence were found. Thus, basic behavioral functions of fast vision may be influenced by common genetic variability. Also, when left uncontrolled, genetic factors may seriously confound variables in vision research using masking, obscure clear theoretical interpretation, lead to unexplicable inter-regional differences and create problems of replicability of formerly successful experiments.

Target-mask shape congruence impacts the type of metacontrast masking.

Visual metacontrast masking may depend on the time intervals between target and mask in two qualitatively different ways: in type-A masking the smaller the mask delay from target the stronger the masking while in type-B masking maximal masking effect is obtained with a larger temporal delay of the mask. Variability in the qualitative apperance of masking functions has been explained by variability in stimuli parameters and tasks. Recent research on metacontrast masking has surprisingly shown that both of these types of functions can be found with an identical range of stimulation parameters depending on individual differences between observers. Here we show that obtaining clear-cut type-A masking depends on whether target and mask shapes are congruent or incongruent and whether observers use the cues available due to the congruence factor. Conspicuously expressed type-A masking is selectively associated with incongruent target-mask pairings. In the latter conditions target identification level significantly drops with the shortest target-to-mask delays.