Autism 2

Autism 2

1. Cause??

   • Refrigerator Mothers? Still not fully understood. But, generally accepted to be largely genetic (Grelotti et al., 2002). No single gene, but multiple interacting genes, and not confined to a particular part of the brain. Combination of several causes which results in problems in how the brain processes and integrates information (which effects social interaction, communication and other aspects of behaviour), Primary cognitive explanations?

2. Genetics

   • Family and twin studies show significant familial loading for autism. Higher concordance for classic autism (about 60%) for identical than non-identical twins (Bailey et al., 1995). Non-concordant twins often found to show broader autism phenotype (Rutter, LeCouteur & Bolton, 1996) as well as family members. Risk of second child (sibling) being affected is 5-10%, 1% prevalence overall. Gillberg (1991) – genetic risk for full spectrum - Autism subgroups run in families – AS/Classic autism. Common genetic aetiology. Capturing the broader autism phenotype (AQ) e.g. traits that are sub-clinical that do not impact functioning e.g. rigidity of behaviour (vary within population), social awkwardness…
   • But – MZ concordance only 60%! Concordance rates of less than 100% indicate other effects Probably environmental, but as of yet unidentified. Hultman et al. (2011) advancing paternal age- Swedish 10-year birth cohort (N= 1 075 588) + meta-analysis of population based epidemiological studies. General consensus for strong genetic basis for ASDs - 1 gene? Different expression of autism symptoms in MZ twins. Pattern of inheritance and range of symptoms indicate polygenetic disorder - International Molecular Study of Autism has identified several gene markers on Chromosomes 2, 7, 15, 16, 17 and 19 (15 & GABA). Work going on about increased paternal age/maternal age? When you control for mental health/health factors and maternal age – there is an increase risk of higher increased paternal age with autism – due to genomic aberration/abnormalities involved in sperm production? --> people have children later now… Birth order effect? (More likely in first born? --> not supported well)
   • Little replication between genetic studies. ‘N’ needs to be very high in genetic research. Several factors making the search for genetic basis difficult. Variability in phenotype of ASDs (IQ, language ability etc) makes well-defined samples difficult to achieve! Different genes could be responsible for different aspects of impairments. Interaction between genetics and environment (see Eapen, 2011 for review). Idea that understanding the profile of cognition in autism is very important so that we can begin to understand and profile heterogeneity

3. Psychological models of ASD

   • Predominance of cognitive theories of ASD in last decade. Cognitive constructs to explain deficits found in ASD - Executive Dysfunction (ED) – neuropsychological skills (papers on DUO). ED - Literature is very mixed – same kind of inconsistency in terms of performance in different tasks on inhibition – problem most robust in shifting (WSCT), planning. Jim Russell: one reason why people with autism struggle with ED task is because they have very arbitrary rules which does not make sense e.g. Windows task.. Not problem with inhibition but about the task. ED does not explain why people with autism do not orient to social information (joint attention, language, pretend play etc.), they also do not predict severity on symptom measures. Weak Central Coherence (WCC) – information processing. Theory of Mind (TOM) - social.
   • Central Coherence Theory
     • First proposed by Uta Frith (1989). Information processing (core deficit). Typical (TD) central coherence (construct). People need/desire high-level meaning, think of it in terms of its global context at the expense of neglect on the local detail. Everyday tendency to process incoming information in context. Weak Central Coherence in ASD (Happe & Frith, 2006). Bias towards featural (piecemeal) processing. Focus on detail rather than integrating information into meaningful wholes (Frith, 1989). Task to test central coherence: rely on visual space
     • Embedded figures test (Frith 2003). Finding "tent" in horse pram picture. Individuals with Autism are faster than typical at completing this task.
       • The ebbinghaus illusion - individuals with autism are not susceptible to this illusion.
     • Weak central coherence and language
       • Read words aloud: ‘Tear’, Tear in the eye, Tear in fabric. double pronunciation. Participants with autism chose wrong pronunciation Happé (1997). Why? Need to put words in context to choose the appropriate pronunciation
     • Navon stimuli - Test of local vs. global processing bias. Small letters make up a big letter. Task: either identify large letters or small letters. If you have strong bias towards local/global processing, then interference effects. Autism: very little consistency of performance, some show local bias, some global
     • WCC explains: Superior visuo-spatial /perceptual skills (Lee et al., 2007; Shah & Frith, 1997) and Learning style in ASDs very well & discrepancies on intelligence test batteries where non-verbal ability (jigsaw-type tests) often exceeds verbal skills. But, Specificity? Prevalence on spectrum not clear. Meta-analysis (Muth et al., 2014). Embedded figures – generally superior, but small group difference and enormous heterogeneity. Block Design – same. Navon stimuli – small effect of stronger local preference, but not universal – not a great margin. ot consistently different, and where you do get the stronger local preference – the effect is quite small. But some evidence of WCC in the broader autism phenotype (Happe et al., 2001). Evidence as to what causes WCC, or when it might emerge? Some evidence that visuo-spatial tasks recruit less frontal activation when performing the task, but this doesn’t link to performance (Muth et al., 2014).
       • No evidence when/where it might emerge in development. A non social explanation of autism.
   • Enhanced perceptual capacity
     • Load Theory of Attention and Cognitive Control (Lavie, 2005). Visual attention tasks contain different amounts of perceptual information. extent to which irrelevant distractors are perceived depends on whether the task exhausts perceptual capacity or leaves some spare capacity that “spills over,” resulting in irrelevant distractor processing. If tasks have: High perceptual load - engage full capacity - no additional processing of irrelevant distractors. Low perceptual load – spill over of remaining capacity - distractor processing.
     • Remington et al 2009 - Identify x or n, with presence of a flanker (sometimes x or n). Low load: central task is easy (right), high load (left) since perceptual load of full, flanker will not be distracting. Task with high load are ones in which individuals with autism seem to do better on as they have an enhanced perceptual capacity – individuals with autism are still able to process the distractor at higher loads compared to TD. Suggest that task that don’t exhaust perceptual capacity, those individuals with autism will continue to process distractors.
       • Remington et al 2012. Enhanced capacity a negative thing if you’re trying to screen out distractors but positive for detection. Explain range of findings in terms of visual abilities, whereby you have enhanced detection/processing and greater distractors --> Both difficulties/strength of visual development in autism
   • Theory of mind
     • Influential theory. Provides explanation of core social impairment in ASDs. ‘Theory of Mind’ is the ability to attribute independent mental states to self and others in order to explain and predict behaviour. To understand another’s mental life. Necessary for empathy….for sarcasm…..for deception. Socio-cognitive milestone: TD children begin to pass TOM tasks around age 4-5. Joint attention, Pretend play Deficits found in ASD (Leekam et al., 2000). Those with autism looked at distracting items in a classroom more than TD and this influenced their learning/performance – enhance capacity as an explanation based on attention? Real utility for understanding …
     • Theory of mind and ASDs
       • Baron-Cohen et al. (1985) used classic ‘Sally-Anne task’ suggested a theory of mind deficit in autism. But Premack and Woodruff (1978) - Do chimpanzee’s have a theory of mind? Most of the TD children (85%) and children with Down syndrome (86%) got it right but only some of the autistic children (20%) did (even though they had a higher mental age than the other children). Smarties task .
         • Sodian & Frith (1992) : To rule out possible effects of not understanding the TOM tasks - Sabotage and Deception (2 conditions). Competitive game with rewards involving friendly rabbit and thieving wolf. If rabbit got candy – then child got two. If wolf got candy – then child got none. Practise – child learns friend/enemy. Nature about the task or actually mentalizing. Options are to lie in deception condition – children with autism cannot reason with this, they can say it was lock but could not physically lock it.
       • Ecological validity
         • Golan, Baron-Cohen & Golan (2008) - recognition of complex emotions & mental states. 23 children with ASD 8 -11 years matched to a group 24 TD children 8 -12 years. Reading the Mind in Films’ Task-Child Version (RMF-C). 27 short dynamic scenes from four children’s films (6-30 secs). Socio-emotional interactions between 1-4characters, involving expression of complex emotions and mental states (e.g. relieved, guilty or lonely). Identify what the character in the scene was feeling by picking an emotion out a list of four possible answers. Cambridge Mindreading Face-Voice Battery-Children Version (CAM-C) - tests recognition of nine complex emotions and mental states. Children with autism scored significantly lower than the TD children on the RMF-C and the CAM-C. Better VIQ associated with better RMF-C in both groups. Scores from both tasks strongly correlated with each other, indicating that the ability to recognise emotions from face and voices is associated.
           • Depicted scenes of emotions, and had to pick an emotion of force choice that represents the films – autism had great difficulty in both tasks – these difficulties in mentalizing are not specific to false-belief tasks.
       • Mental state attribution from animated shapes (Castelli et al., 2002). Individuals with autism use less mental states terms. Related to function of ‘social brain’ (e.g. MPC, STS). Pattern of brain activation when watching these clips are very different in those with autism – but we spontaneously attributed mental perspectives & relates to pattern of social brain activity but we do not see these in autism – underpins mentalizing ability
       • Plausible account of social impairment in ASDs. Sharing, misunderstandings, pretend play & typical childhood games. Some communication difficulties – deception, sarcasm, and literal interpretation. ‘Mentalizing’ related to patterns of brain activation (Medial Prefrontal Cortex and Superior Temporal Sulcus) (Castelli et al., 2000). Majority of research has used False Belief Tasks. BUT - not all individuals with ASDs fail TOM tasks! Issue with false belief task… not all FAIL (20% of those with autism pass these sort of task) – due partly to relationship between performance and verbal IQ/ability
       • Limitations to Theory of Mind
         • FBTs - Only useful with individuals with good receptive language. About 20% are successful on FBTs varying in levels of complexity (Happé & Frith, 1996; Hoogenhout & Malcolm-Smith, 2014). They may represent the higher functioning end of the spectrum (more like AS). FBTs – verbally mediated. Relationship between verbal ability and passing TOM tasks. Problem solving task? Even those who pass second order FBTs have many social interaction difficulties. To some degree, what is being tested here is language, those who pass struggle with daily interaction (not that they have better mentalizing abilities as it does not translate to real life behaviour)
           • Senju et al 2009 - Eye tracking to circumvent language confound. Participants with AS Significantly less looking to the correct window (the one consistent with the actor’s false belief). Authors suggest that adults with AS do not spontaneously anticipate other’s action in a nonverbal task, which is modelled on the paper and pen version that they pass with ease. Created videos depicting a false belief task – series of familiarization trials, puppet moving ball from one to another, windows flash at different windows and experimenter puts hand in the window to get the ball
           • Teaching of ToM skills does not translate into better social competence. ToM impairments not specific to ASD (congenital blindness; late signing deaf children, Peterson, Wellman & Lui, 2005). ToM deficit cannot account for non-social impairments (inflexibility of thought) in ASD or islets of ability (savants). Has a limitation to social aspect of the disorder

4. Discussion

   • If there are several cognitive impairments associated with autism, should explanations such as ToM or EF or WCC be abandoned?
     • Fractionation
       • Dominant cog theories generated much research, and have led to important insights, but struggled to provide complete accounts of autism. Is it important to find one cause for autism? Fractionation of the triad. Should autism be viewed as a fractional set of symptoms or a disorder that is coherent (Hobson, 2014)? Assumed that symptoms of autism cluster together with an underlying neurodevelopmental basis, which implies a unitary explanation. Happé and Ronald (2008) - research exploring the causes of ASD has been disadvantaged by this assumption, and that autism manifests when three groups of independent symptoms occur together. Held back research in the area? Impairments of autism in fractions and not related? Genetic and heritability can be different for those on the spectrum – finding one explanation may not be sensible… Little work looking at performance on WCC, ToM and ED together – again because the framework is to look at each one in turn and who it explains everything
   • Current Directions
     • Various evidence that brains of individuals with ASDs are different: Social Brain - Medial Prefrontal Cortex, Superior Temporal Sulcus, Amygdala, FFA. Fusiform Face Area- Expertise. Individuals with autism learn about the world and particularly the social world differently (Dawson et al., 2008). Up to now, relatively high level of explanation. Increased capacity with ability to focus on autism to think about very early development (especially at-risk children) tracking them longitudinally. Good evidence that individuals with autism do not become experts in processing social information.

5. Social motivation theory

   • Is an approach that is not trying to understand and explain the non-social aspects of autism --> but reciprocal social difficulties due to a lack of social motivation. Cross several different pathways and areas of impairment that could lead to various other pathways. Manifestation of social motivation in terms of orienting and desire to seek and maintain social interaction.
   • Social motivation in ASD
     • Due to lack of reward in the biological level that translate to lack of interest in people which has a knock-on effect on social experience and social learning. Equally, it may manifest into interest of things/non-social information. Making predictions based on early social attention patterns
     • Evidence from neurological, behavioural and qualitative data. Disrupted ‘reward-seeking’ in ASD, especially in social context including brain regions of ventral striatum, amygdala, and vmPFC (review by Kohls et al., 2012). Stronger tendency to approach social and non-social stimuli in children with ASD (Deckers et al., 2014). Diminished self-reported of enjoyment in social situations (but not in physical and other sources) in children with high-functioning ASD (Chevallier et al., 20120).

6. Amygdala and ASD

   • Amygdala associated with arousal and processing of social/emotion info (part of the ‘social brain’). Evaluating the emotional significance of external events. Altered motivation comes from the amygdala (associated with arousal and processing of social/emotional information), evaluating emotional significance of external events
     • Dalton et al 2005. Study 1 - emotional discrimination task while eye tracking (neutral/emotion response). Study 2 – familiar face judgements. Participants with ASD – diminished looking to eye regions across both studies. Increased activation of the amygdala for participants with ASD when fixating the eyes. Participants with ASD who had the smallest amygdalae showed the least fixation to the eyes. Hyper-activation of the Amygdala – eyes are aversive. Paired social attention to faces with neurofunctions in children with autism. Positive association is not attached, resulting in the failure to attend. Hyper or hypo arousal, aversive or not rewarding enough? Still have heterogeneity on the biological level. Eye-tracking: ask them about experiences on eye-contact and they say very different things
       • Fear conditioning
         • Top et al. (2016) fear conditioning. 42% of blue trials, you’ll get a puff of air to the neck (surprising) … learn association of this. Second day, go through extinction trials. TD: greater activation amygdala to blue stimuli in extinction, fear conditioned response. Autism: do not get differentiation in response. Greater base-line activation in amygdala in autism, threat and safe cues difficult to distinguish in ASD…. As well as generally above threshold for emotional stimuli. Difficult learning to differentiate between threat and safe cues, and delayed fear extinction in ASD
   • Some evidence to suggest that the amygdala is less active than TD in response to emotional face (Baron-Cohen et al., 1999) Hypo-activation model (positive reward never attached, resulting in failure to attend and reduced salience of faces and eyes)

7. Current directions

   • Pellicano (2013) sensory processing. Hypo priors. South & Rodgers (2017). Sensory processing: if atypical across various modalities and it is distressing – assume learning basic associations will be quite different, if sensory information very reliable… again difficult to learn basic association – makes the world uncertain and unreliable, explanation for development of anxiety and repetitive behaviours. Tran-diagnostic construct that tries to explain your tolerance of uncertainty - how much predictability you can cope with. Various senses can cause distress
     • At risk sibs
       • Bedford et al. (2014) - Attentional measures in at-risk sibs. Gaze following and attentional disengagement. 13-month measures independently predicted ASD outcome at 3 years of age. Non-social attention, disengagement, and social attention as evidenced by gaze following, have a cumulative impact on ASD risk (best model is additive – not single underlying pathway). High-risk infants who show reduced looking time to the object, and slower disengagement, more likely to develop ASD. Gap overlap task, central attention capturing stimulus and a peripheral stimulus. Best model for predicting outcome is an additive one – performance across domains of social/non-social attention.

8. Summary

   • Profile of strengths and weaknesses in Autism, including central coherence, theory of mind and executive functioning, which are largely unrelated to each other. Provide independent contributions to how we understand autism. There is not one deficit, but several underlying strengths and weaknesses that co-occur in ASD. Challenge – heterogeneity. Studies of cognition and behaviour very important - phenotyping. Focus on at-risk sibs.

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