Cross-modal perceptual integration : studies in autism, the broader autism phenotype and typical development

Integration of sound and vision is important for humans to interact efficiently with their environment. Co-occurrence of sensory inputs in space and time orients attention (Spence & McDonald, 2004), highlights causal relationships between events (Blakemore et al. (2001), and enhances representational formation from infancy (Jordan et al., 2006). Dysfunction within the neural mechanisms supporting multisensory processing hypothetically has widespread consequences, particularly in terms of social interaction as social stimuli are feature-rich and cross-modal. People with autism spectrum disorders are diagnosed on the basis of atypical behaviours relating to social interaction. Iarocci and McDonald (2006) consider that subjective perceptual incoherence in individuals with ASD reflect dysfunctional multisensory processing which may be causal to development of autism. Evidence of superior vision processing in ASD supports the idea that enhanced perceptual functioning (EPF) is an important part of the autism phenotype (Mottron et al., 2006). Bertone and Faubert (2006) propose that perceptual integration within single modalities is compromised, resulting in elevated simple stimulus feature processing. Their Signal Integration Theory (SIT) accommodates superiorities in autistic task performance that are theoretically related to a cognitive preference for detail-processing (Weak Central Coherence theory Happe' & Frith, 2006). In this thesis, a cross-modal phenomenon was selected assessing multisensory processing in typical children, adults with autistic traits and children with ASD. Processing cross-modal perceptual stimuli (Sekuler et al., 1997) relates to perceptual system functioning (Bushara et al., 2003) and is theoretically relevant to the development of intuitive physics (Michotte, 1963), a cognitive process spared in ASD (Baron-Cohen, Wheelwright, Scahill, Lawson & Spong, 2001). Visual disembedding and intuitive physics tasks show gender differences (Halpern et al., 2007). Sex differentiation in cognition has led to the Extreme Male Brain theory of Autism (Baron-Cohen, 2002), in which autistic 'traits' are expressed in everyone to some extent ASD is described as representing extreme male brain functioning at one end of a continuum, the other end representing the 'extreme female brain'. Research using adapted cross-modal perceptual stimuli is presented. This evaluates whether cross-modal integration is compromised in relation to autism. Gender, autistic trait expression and perception/cognition relationships between cross-modal causality and intuitive figures/visual disembedding are also researched to determine whether ASD might, in future, be remodelled in terms of extreme male perceptual development.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Cross-modal perceptual integration: Studies in autism, the broader autism phenotype and typical development

Integration of sound and vision is important for humans to interact efficiently with their environment. Co-occurrence of sensory inputs in space and time orients attention (Spence & McDonald, 2004), highlights causal relationships between events (Blakemore et al. (2001), and enhances representational formation from infancy (Jordan et al., 2006). Dysfunction within the neural mechanisms supporting multisensory processing hypothetically has widespread consequences, particularly in terms of social interaction as social stimuli are feature-rich and cross-modal. People with autism spectrum disorders are diagnosed on the basis of atypical behaviours relating to social interaction. Iarocci and McDonald (2006) consider that subjective perceptual incoherence in individuals with ASD reflect dysfunctional multisensory processing which may be causal to development of autism. Evidence of superior vision processing in ASD supports the idea that enhanced perceptual functioning (EPF) is an important part of the autism phenotype (Mottron et al., 2006). Bertone and Faubert (2006) propose that perceptual integration within single modalities is compromised, resulting in elevated simple stimulus feature processing. Their Signal Integration Theory (SIT) accommodates superiorities in autistic task performance that are theoretically related to a cognitive preference for detail-processing (Weak Central Coherence theory Happe' & Frith, 2006). In this thesis, a cross-modal phenomenon was selected assessing multisensory processing in typical children, adults with autistic traits and children with ASD. Processing cross-modal perceptual stimuli (Sekuler et al., 1997) relates to perceptual system functioning (Bushara et al., 2003) and is theoretically relevant to the development of intuitive physics (Michotte, 1963), a cognitive process spared in ASD (Baron-Cohen, Wheelwright, Scahill, Lawson & Spong, 2001). Visual disembedding and intuitive physics tasks show gender differences (Halpern et al., 2007). Sex differentiation in cognition has led to the Extreme Male Brain theory of Autism (Baron-Cohen, 2002), in which autistic 'traits' are expressed in everyone to some extent ASD is described as representing extreme male brain functioning at one end of a continuum, the other end representing the 'extreme female brain'. Research using adapted cross-modal perceptual stimuli is presented. This evaluates whether cross-modal integration is compromised in relation to autism. Gender, autistic trait expression and perception/cognition relationships between cross-modal causality and intuitive figures/visual disembedding are also researched to determine whether ASD might, in future, be remodelled in terms of extreme male perceptual development

Mechanistic insights into a BINOL-derived phosphoric acid-catalyzed asymmetric Pictet-Spengler reaction.

The reaction of tryptamine and (2-oxocyclohexyl)acetic acid can be catalyzed by 3,3'-bis(triphenylsilyl)-1,1'-bi-2-naphthol phosphoric acid to give an asymmetric β-carboline. This reaction was first studied by Holloway et al. ( Org. Lett. 2010 , 12 , 4720 - 4723 ), but their mechanistic work did not explain the high stereoselectivity achieved. This study uses density functional theory and hybrid quantum mechanics/molecular mechanics calculations to investigate this reaction and provide a model to explain its outcome. The step leading to diastereo- and enantioselectivity is an asymmetric Pictet-Spengler reaction involving an N-acyliminium ion bound to the catalyst in a bidentate fashion. This interaction occurs via hydrogen bonds between the two terminal oxygen atoms of the catalyst phosphate group and the hydrogen atoms at N and C2 of the substrate indole group. These bonds hold the transition structure rigidly and thus allow the catalyst triphenylsilyl groups to influence the enantioselectivity.We thank Girton College, Cambridge (research fellowship to M.N.G.), the EPSRC (studentship to M.N.G.), and Unilever for support.The is the final published version. It first appeared at http://pubs.acs.org/doi/abs/10.1021/jo5028134

Impaired conditional task performance in a high schizotypy population: Relation to cognitive deficits

Cognitive impairments in schizophrenia have been characterized as reflecting a core deficit in the maintenance or use of task-setting cues to mediate appropriate ongoing behaviour. This analysis suggests that cognitive deficits in schizophrenia will be particularly evident when different task-setting cues dictate when different responses are required by the same stimuli. One simple task in which task-setting cues are required is a biconditional discrimination. Here we examined the performance of participants with high and low schizotypy scores (Mason, Claridge, Jackson, 1995) on a biconditional discrimination and an otherwise equivalent, control discrimination that did not require the use of task-setting cues. Participants scoring highly on the Introvertive Anhedonia subscale (which has been allied to the negative and cognitive symptoms of schizophrenia) performed poorly on the biconditional, but not on the control, discrimination. No other subscales demonstrated a significant influence on either biconditional or control performance

Extreme elemental processing in a high schizotypy population: Relation to cognitive deficits

The cognitive deficits observed in schizophrenia have been characterized as a failure to utilize task-setting information to guide behaviour, especially in situations in which there is response conflict. Recently, we have provided support for this account; high schizotypy individuals demonstrated inferior biconditional discrimination performance compared to low scorers, but were not impaired on a simple discrimination that did not require the use of task-setting cues. These results may, however, also be explained by the way in which individuals with high schizotypy process stimulus compounds. Here, we examine the initial approaches to solving biconditional and control discrimination tasks of participants wit h high and low schizotypy scores. In particular, we focus on performance during the first block of training trials to capture processing style before the acquisition of the discrimination tasks. Participants scoring highly on the introvertive anhedonia subscale (which has been allied to the negative and cognitive symptoms of schizophrenia) demonstrated better biconditional performance during the first block of training trials than did low-schizotypy individuals, consistent with a highly elemental approach to stimulus processing. Subsequent recognition tests confirmed this analysis demonstrating that the pattern of performance observed in participants with high schizotypy was associated with a failure to discriminate conjunctions of items that had been seen before from those that had not. These results suggest that the negative/cognitive symptoms of schizophrenia may reflect an extreme bias towards elemental, as opposed to configural, processing of stimulus conjunctions. © 2013 © 2013 The Experimental Psychology Society

A validation of cognitive biomarkers for the early identification of cognitive enhancing agents in schizotypy:a three-center double-blind placebo-controlled study

A number of compounds aimed at improving cognition in schizophrenia have failed to demonstrate efficacy in Phase 2 clinical trials. Translational studies using biomarkers in surrogate populations, such as schizotypy, could be used to assess the efficacy of novel compounds. In this study, we aimed to validate the sensitivity and inter-site reliability of cognitive biomarkers (working memory (N-back), spatial working memory (SWM) and verbal fluency (VF) tasks) to detect the schizotypy phenotype and its reversal by psychotropic drugs. Healthy volunteers scoring high or average on a schizotypal personality measure (122 in each group) were randomized to receive a single dose of risperidone, amisulpride, nicotine or placebo in a double-blind, between-subject design. We found evidence for a poorer performance on N-back and VF tasks in the high schizotypy group, replicating previous research. This effect was counteracted by amisulpride on N-back: it improved working memory in high schizotypy group but impaired the controls. A similar pattern was seen in SWM and VF. We interpret this finding in the light of the dopamine enhancing action of amisulpride when given in low doses. In contrast, risperidone impaired both groups and nicotine had a beneficial effect for the low baseline performers only. These effects were consistent across sites. These data demonstrates the utility of biomarkers in detecting the effect of schizotypy and its reversal by drugs that enhance dopamine and cholinergic function. Studies using similar design could help the early assessment of potential of compounds designed to improve cognition in schizophrenia