Associating LIPS and SWOLLEN: delayed attentional disengagement following words in sex contexts.

With a series of three studies, using an adapted dot-probe paradigm, we investigated the elicitation of spontaneous affective meaning. Although it is well established that humans show delays in disengaging their attention from conventional affective stimuli, it is unknown whether contextually acquired affective meaning similarly impacts attention. We examined attentional disengagement following pairs of neutral or slightly ambiguous words that in combination could evoke sex, violence or neutral associations. Study 1 demonstrated slower disengagement following words that conveyed sex or violence associations compared to words that conveyed neutral associations. This pattern was only present for participants who were aware of sex or violence associations. Study 2 replicated these results in a large sample, but only for sex associations. Study 3 replicated the effect while instructing participants explicitly to expect sex and violence associations. Finally, two control studies countered reasonable alternative explanations for our findings. Together, these studies show that contextually driven affective associations can arise quickly with the potential to influence attentional processes. These findings are consistent with theoretical models of emotion and language that highlight the importance of context in the generation of affective meaning.

Bottom-up and top-down attention are independent.

What is the relationship between top-down and bottom-up attention? Are both types of attention tightly interconnected, or are they independent? We investigated this by testing a large representative sample of the Dutch population on two attentional tasks: a visual search task gauging the efficiency of top-down attention and a singleton capture task gauging bottom-up attention. On both tasks we found typical performance--i.e., participants displayed a significant search slope on the search task and significant slowing caused by the unique, but irrelevant, object on the capture task. Moreover, the high levels of significance we observed indicate that the current set-up provided very high signal to noise ratios, and thus enough power to accurately unveil existing effects. Importantly, in this robust investigation we did not observe any correlation in performance between tasks. The use of Bayesian statistics strongly confirmed that performance on both tasks was uncorrelated. We argue that the current results suggest that there are two attentional systems that operate independently. We hypothesize that this may have implications beyond our understanding of attention. For instance, it may be that attention and consciousness are intertwined differently for top-down attention than for bottom-up attention.

From adaptive to maladaptive fear: Heterogeneity in threat and safety learning across response systems in a representative sample.

Individual differences in fear learning are a crucial prerequisite for the translational value of the fear-conditioning model. In a representative sample (N = 936), we used latent class growth models to detect individual differences in associative fear learning. For a series of subsequent test phases varying in ambiguity (i.e., acquisition, extinction, generalization, reinstatement, and re-extinction), conditioned responding was assessed on three response domains (i.e., subjective distress, startle responding, and skin conductance). We also associated fear learning across the different test phases and response domains with selected personality traits related to risk and resilience for anxiety, namely Harm Avoidance, Stress Reaction, and Wellbeing (MPQ; Tellegen and Waller, 2008). Heterogeneity in fear learning was evident, with fit indices suggesting subgroups for each outcome measure. Identified subgroups showed adaptive, maladaptive, or limited-responding patterns. For subjective distress, fear and safety learning was more maladaptive in the subgroups high on Harm Avoidance, while more adaptive learning was observed in subgroups with medium Harm Avoidance and the limited- or non-responders were lowest in Harm Avoidance. Distress subgroups did not differ in Stress Reaction or Wellbeing. Startle and SCR subgroups did not differ on selected personality traits. The heterogeneity in fear-learning patterns resembled risk and resilient anxiety development observed in real life, which supports the associative fear-learning paradigm as a useful translational model for pathological fear development.

Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use.

BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk. METHODS: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci. RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals. CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.

Exploring the role of low-frequency and rare exonic variants in alcohol and tobacco use.

BACKGROUND: Alcohol and tobacco use are heritable phenotypes. However, only a small number of common genetic variants have been identified, and common variants account for a modest proportion of the heritability. Therefore, this study aims to investigate the role of low-frequency and rare variants in alcohol and tobacco use. METHODS: We meta-analyzed ExomeChip association results from eight discovery cohorts and included 12,466 subjects and 7432 smokers in the analysis of alcohol consumption and tobacco use, respectively. The ExomeChip interrogates low-frequency and rare exonic variants, and in addition a small pool of common variants. We investigated top variants in an independent sample in which ICD-9 diagnoses of "alcoholism" (N = 25,508) and "tobacco use disorder" (N = 27,068) had been assessed. In addition to the single variant analysis, we performed gene-based, polygenic risk score (PRS), and pathway analyses. RESULTS: The meta-analysis did not yield exome-wide significant results. When we jointly analyzed our top results with the independent sample, no low-frequency or rare variants reached significance for alcohol consumption or tobacco use. However, two common variants that were present on the ExomeChip, rs16969968 (p = 2.39 × 10-7) and rs8034191 (p = 6.31 × 10-7) located in CHRNA5 and AGPHD1 at 15q25.1, showed evidence for association with tobacco use. DISCUSSION: Low-frequency and rare exonic variants with large effects do not play a major role in alcohol and tobacco use, nor does the aggregate effect of ExomeChip variants. However, our results confirmed the role of the CHRNA5-CHRNA3-CHRNB4 cluster of nicotinic acetylcholine receptor subunit genes in tobacco use.

Are Autistic Traits in the General Population Related to Global and Regional Brain Differences?

There is accumulating evidence that autistic-related traits in the general population lie on a continuum, with autism spectrum disorders representing the extreme end of this distribution. Here, we tested the hypothesis of a possible relationship between autistic traits and brain morphometry in the general population. Participants completed the short autism-spectrum quotient-questionnaire (AQ); T1-anatomical and DWI-scans were acquired. Associations between autistic traits and gray matter, and white matter microstructural-integrity were performed on the exploration-group (N = 204; 105 males, M-age = 22.85), and validated in the validation-group (N = 304; 155 males, M-age = 22.82). No significant associations were found between AQ-scores and brain morphometry in the exploration-group, or after pooling the data. This questions the assumption that autistic traits and their morphological associations do lie on a continuum in the general population.

Emotional facial expressions reduce neural adaptation to face identity.

In human social interactions, facial emotional expressions are a crucial source of information. Repeatedly presented information typically leads to an adaptation of neural responses. However, processing seems sustained with emotional facial expressions. Therefore, we tested whether sustained processing of emotional expressions, especially threat-related expressions, would attenuate neural adaptation. Neutral and emotional expressions (happy, mixed and fearful) of same and different identity were presented at 3 Hz. We used electroencephalography to record the evoked steady-state visual potentials (ssVEP) and tested to what extent the ssVEP amplitude adapts to the same when compared with different face identities. We found adaptation to the identity of a neutral face. However, for emotional faces, adaptation was reduced, decreasing linearly with negative valence, with the least adaptation to fearful expressions. This short and straightforward method may prove to be a valuable new tool in the study of emotional processing.