DNA chip the what's, the why's and the how's

This article presents a brief overview of DNA chips, or microarrays. Microarrays are a very significant technological development in molecular biology, and are perhaps the most efficient tool available for functional genomics today

Atypical reward-driven modulation of mimicry-related neural activity in autism

Autism spectrum disorder (ASD) is characterized by deficits in social functioning and difficulties in forming social bonds. According to the social motivation theory of ASD, people with ASD fail to attend social stimuli because they do not experience them as rewarding, resulting in deficits in social cognition. In neurotypical (NT) individuals, more rewarding faces have been shown to elicit greater spontaneous facial mimicry. This association between reward and mimicry is reduced in people with high autistic traits, suggesting that altered reward processing might explain the deficits in spontaneous facial mimicry observed in individuals with ASD. In a previous study, we observed that learned reward value of a face modulates mimicry-related neural response to it and that this modulation is reduced in people with high autistic traits. Using an identical evaluative conditioning paradigm where neutral faces were conditioned with high and low rewards, we tested the modulating effect of reward value on mimicry-related brain activity in a group of adults with and without ASD. We focused on the activity in a cluster within the inferior frontal gyrus (IFG) identified through an independent meta-analysis of 139 neuroimaging studies of mimicry, in response to passively viewing videos of the conditioned faces. The blood oxygen level dependent (BOLD) response contrast of high- vs. low-reward faces was reduced in participants with ASD compared to NT controls. The extent of reward-driven modulation was negatively correlated with autistic traits across the whole sample. Our results indicate that the mimicry-related brain response is less modulated by learned reward value in individuals with ASD when compared to NT controls. In previous studies, we found in a similar sample that being mimicked by faces was associated with less reward-related brain response in individuals ASD compared to an NT sample, suggesting that the link between reward and mimicry is affected in both directions in ASD. Together, this reduced bidirectional link between reward and mimicry can point to a potential mechanism underlying some of the social cognitive features of ASD

Autistic differences in the temporal dynamics of social attention

Individuals with autism spectrum disorders (ASD) typically exhibit reduced visual attention towards social stimuli relative to neurotypical (NT) individuals. Importantly however, attention is not a static process, and it remains unclear how such effects may manifest over time. Exploring these momentary changes in gaze behavior can more clearly illustrate how individuals respond to social stimuli and provide insight into the mechanisms underlying reduced social attention in ASD. Using a simple passive eye-tracking task with competing presentations of social and nonsocial stimuli, we examine the different ways in which attention to social stimuli evolves over time in NT and ASD adults. Our temporal modeling of gaze behavior revealed divergent temporal profiles of social attention in NT and ASD observers. NT data showed an initial increase in social attention, a ‘decay’ and subsequent ‘recovery’ after prolonged viewing. By contrast, in ASD, social attention decayed over time in a linear fashion without recovery after prolonged viewing. We speculate that the ‘gaze cascade’ effect that maintains selection of social stimuli in NT observers is disrupted in individuals with high autistic traits. Considering these temporal components of gaze behavior may enhance behavioral phenotypes and theories of social attention in ASD

Empathy modulates the temporal structure of social attention

Individuals with low empathy often show reduced attention towards social stimuli. A limitation of this literature is the lack of empirical work that has explicitly characterized how this relationship manifests itself over time. We investigate this issue by analysing data from two large eye-tracking datasets (total n = 176). Via growth-curve analysis, we demonstrate that self-reported empathy (as measured by the empathy quotient—EQ) predicts the temporal evolution of gaze behaviour under conditions where social and non-social stimuli compete for attention. In both datasets, we found that EQ not only predicted a global increase in social attention, but predicted a different temporal profile of social attention. Specifically, we detected a reliable effect of empathy on gaze towards social images after prolonged viewing. An analysis of switch latencies revealed that low-EQ observers switched gaze away from an initially fixated social image more frequently and at earlier latencies than high-EQ observers. Our analyses demonstrate that modelling these temporal components of gaze signals may reveal useful behavioural phenotypes. The explanatory power of this approach may provide enhanced biomarkers for conditions marked by deficits in empathy-related processes

Thinking about others and the future: neural correlates of perspective taking relate to preferences for delayed rewards

We infer the thoughts and feelings of others by taking their perspectives. Similar processes could be used to understand how we will be affected by future events, by allowing us to take the perspective of our future self. In this paper, we test this idea using a previously presented framework for guiding predictions. The framework proposes that a shared neural mechanism is involved in controlling egocentric bias, both while shifting our perspective away from self and towards others, and while shifting our perspective from immediate to future perspectives. To test this framework, 36 adults performed an intertemporal choice task. They were then scanned using 3T functional magnetic resonance imaging while completing a false-belief “localizer” task, which requires egocentric bias control. A positive correlation was observed between the right temporoparietal junction (rTPJ) response during the false-belief task, and preferences for delayed rewards in intertemporal choices. A subset of participants performed the intertemporal choice task again in the scanner, which revealed that the response of the same rTPJ cluster, individually localized during the false-belief task, was higher during delayed over immediate reward choices. In addition, functional connectivity between the rTPJ and ventromedial prefrontal cortex was found to differ between immediate and delayed choices. The current results indicate an overlap in processes of egocentric bias control and those that determine preferences in intertemporal choices, offering a social cognitive explanation for why rewards are devalued with delay in temporal discounting

Genetic variant rs17225178 in the ARNT2 gene is associated with Asperger Syndrome.

BACKGROUND: Autism Spectrum Conditions (ASC) are neurodevelopmental conditions characterized by difficulties in communication and social interaction, alongside unusually repetitive behaviours and narrow interests. Asperger Syndrome (AS) is one subgroup of ASC and differs from classic autism in that in AS there is no language or general cognitive delay. Genetic, epigenetic and environmental factors are implicated in ASC and genes involved in neural connectivity and neurodevelopment are good candidates for studying the susceptibility to ASC. The aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) gene encodes a transcription factor involved in neurodevelopmental processes, neuronal connectivity and cellular responses to hypoxia. A mutation in this gene has been identified in individuals with ASC and single nucleotide polymorphisms (SNPs) have been nominally associated with AS and autistic traits in previous studies. METHODS: In this study, we tested 34 SNPs in ARNT2 for association with AS in 118 cases and 412 controls of Caucasian origin. P values were adjusted for multiple comparisons, and linkage disequilibrium (LD) among the SNPs analysed was calculated in our sample. Finally, SNP annotation allowed functional and structural analyses of the genetic variants in ARNT2. We tested the replicability of our result using the genome-wide association studies (GWAS) database of the Psychiatric Genomics Consortium (PGC). RESULTS: We report statistically significant association of rs17225178 with AS. This SNP modifies transcription factor binding sites and regions that regulate the chromatin state in neural cell lines. It is also included in a LD block in our sample, alongside other genetic variants that alter chromatin regulatory regions in neural cells. CONCLUSIONS: These findings demonstrate that rs17225178 in the ARNT2 gene is associated with AS and support previous studies that pointed out an involvement of this gene in the predisposition to ASC.BC was funded by the Medical Research Council UK and VW was funded by the Nehru Trust for Cambridge University and the Cambridge Commonwealth Trust. We thank Robert Plomin, Frank Dudbridge, Lindsey Kent and Ian Craig for relevant discussions, and Jon Breidbord, Allen Chan, Sylvia Lakatosova, Sally Wheelwright, Carrie Allison, Uma Mallya, Alex Politt and Leena Peltonen for support at different points of the project. The study was carried out in collaboration with the NIHR CLAHRC EoE.This is the final published version. It first appeared at http://www.molecularautism.com/content/6/1/9

Genetic variation in the oxytocin receptor (OXTR) gene is associated with Asperger Syndrome

Background Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterized by impairments in communication and social interaction, alongside unusually repetitive behaviors and narrow interests. ASC are highly heritable and have complex patterns of inheritance where multiple genes are involved, alongside environmental and epigenetic factors. Asperger Syndrome (AS) is a subgroup of these conditions, where there is no history of language or cognitive delay. Animal models suggest a role for oxytocin (OXT) and oxytocin receptor (OXTR) genes in social-emotional behaviors, and several studies indicate that the oxytocin/oxytocin receptor system is altered in individuals with ASC. Previous studies have reported associations between genetic variations in the OXTR gene and ASC. Methods The present study tested for an association between nine single nucleotide polymorphisms (SNPs) in the OXTR gene and AS in 530 individuals of Caucasian origin, using SNP association test and haplotype analysis. Results There was a significant association between rs2268493 in OXTR and AS. Multiple haplotypes that include this SNP (rs2268493-rs2254298, rs2268490-rs2268493-rs2254298, rs2268493-rs2254298-rs53576, rs237885-rs2268490-rs2268493-rs2254298, rs2268490-rs2268493-rs2254298-rs53576) were also associated with AS. rs2268493 has been previously associated with ASC and putatively alters several transcription factor-binding sites and regulates chromatin states, either directly or through other variants in linkage disequilibrium (LD). Conclusions This study reports a significant association of the sequence variant rs2268493 in the OXTR gene and associated haplotypes with AS

Emotional responses to Hindustani raga music: the role of musical structure

In Indian classical music, ragas constitute specific combinations of tonic intervals potentially capable of evoking distinct emotions. A raga composition is typically presented in two modes, namely, alaap and gat. Alaap is the note by note delineation of a raga bound by a slow tempo, but not bound by a rhythmic cycle. Gat on the other hand is rendered at a faster tempo and follows a rhythmic cycle. Our primary objective was to (1) discriminate the emotions experienced across alaap and gat of ragas, (2) investigate the association of tonic intervals, tempo and rhythmic regularity with emotional response. 122 participants rated their experienced emotion across alaap and gat of 12 ragas. Analysis of the emotional responses revealed that (1) ragas elicit distinct emotions across the two presentation modes, and (2) specific tonic intervals are robust predictors of emotional response. Specifically, our results showed that the ‘minor second’ is a direct predictor of negative valence. (3) Tonality determines the emotion experienced for a raga where as rhythmic regularity and tempo modulate levels of arousal. Our findings provide new insights into the emotional response to Indian ragas and the impact of tempo, rhythmic regularity and tonality on it

EXPRESS: The integration of head and body cues during the perception of social interactions

Humans spend a large proportion of time participating in social interactions. The ability to accurately detect and respond to human interactions is vital for social functioning, from early childhood through to older adulthood. This detection ability arguably relies on integrating sensory information from the interactants. Within the visual modality, directional information from a person’s eyes, head, and body are integrated to inform where another person is looking and who they are interacting with. To date, social cue integration research has focused largely on the perception of isolated individuals. Across two experiments, we investigated whether observers integrate body information with head information when determining whether two people are interacting, and manipulated frame of reference (one of the interactants facing observer vs. facing away from observer) and the eye-region visibility of the interactant. Results demonstrate that individuals integrate information from the body with head information when perceiving dyadic interactions, and that integration is influenced by the frame of reference and visibility of the eye-region. Interestingly, self-reported autistics traits were associated with a stronger influence of body information on interaction perception, but only when the eye-region was visible. This study investigated the recognition of dyadic interactions using whole-body stimuli while manipulating eye visibility and frame of reference, and provides crucial insights into social cue integration, as well as how autistic traits affect cue integration, during perception of social interactions

Variations in the human cannabinoid receptor (CNR1) gene modulate striatal responses to happy faces.

Happy facial expressions are innate social rewards and evoke a response in the striatum, a region known for its role in reward processing in rats, primates and humans. The cannabinoid receptor 1 (CNR1) is the best-characterized molecule of the endocannabinoid system, involved in processing rewards. We hypothesized that genetic variation in human CNR1 gene would predict differences in the striatal response to happy faces. In a 3T functional magnetic resonance imaging (fMRI) scanning study on 19 Caucasian volunteers, we report that four single nucleotide polymorphisms (SNPs) in the CNR1 locus modulate differential striatal response to happy but not to disgust faces. This suggests a role for the variations of the CNR1 gene in underlying social reward responsivity. Future studies should aim to replicate this finding with a balanced design in a larger sample, but these preliminary results suggest neural responsivity to emotional and socially rewarding stimuli varies as a function of CNR1 genotype. This has implications for medical conditions involving hypo-responsivity to emotional and social stimuli, such as autism.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are