Domain-general versus domain-specific learning mechanisms: Neurochemical mechanisms and relevance to autism

The theory that various features of autism spectrum disorders (ASD) can be explained by differences in the learning (or “predictive coding”) process is growing in popularity. However, extant studies have focused on the domain of sensory perception, i.e., learning what to expect in the visual or auditory domains. It is thus unclear whether such models are restricted to the perceptual domain, or whether they are outlining differences in domain- general learning processes. Consequently, how such theories can explain the social and motor features of ASD is currently unclear. The first part of the current thesis asks whether autistic adults exhibit differences, compared to non-autistic adults, with respect to social learning and motor learning. The second part of this thesis focuses in detail on one of these learning types - social learning. Here I investigate the neurochemical mechanisms that underpin social learning and ask whether they are dissociable from the neurochemical mechanisms that underpin learning from one’s own individual experience (individual learning). In integrating these results with the wider literature, I reflect upon the broader question of whether there are common domain-general learning mechanisms, or domain (e.g., social, motor, individual) specific learning “modules”. Together the studies presented in this thesis implicate the dopaminergic neurotransmitter system in both social and individual learning. Results support the view that there are domain-general neurochemical mechanisms that support various types of learning. These results do not, however, support the view that autistic adults exhibit differences in these domain-general learning processes. That is, our empirical work showed no differences in either social or motor learning when comparing autistic and non-autistic adults. These results do not add support for impaired predictive coding as a core deficit that can explain social and motor atypicalities in autism, but rather force us to think more critically about what overarching conclusions can be drawn from studies of predictive coding in autism within the perception domain

Disruption of dopamine D2/D3 system function impairs the human ability to understand the mental states of other people

Difficulties in reasoning about others’ mental states (i.e., mentalising/Theory of Mind) are highly prevalent among disorders featuring dopamine dysfunctions (e.g., Parkinson’s disease) and significantly affect individuals’ quality of life. However, due to multiple confounding factors inherent to existing patient studies, currently little is known about whether these sociocognitive symptoms originate from aberrant dopamine signalling or from psychosocial changes unrelated to dopamine. The present study, therefore, investigated the role of dopamine in modulating mentalising in a sample of healthy volunteers. We used a double-blind, placebo-controlled procedure to test the effect of the D2/D3 antagonist haloperidol on mental state attribution, using an adaptation of the Heider and Simmel (1944) animations task. On 2 separate days, once after receiving 2.5 mg haloperidol and once after receiving placebo, 33 healthy adult participants viewed and labelled short videos of 2 triangles depicting mental state (involving mentalistic interaction wherein 1 triangle intends to cause or act upon a particular mental state in the other, e.g., surprising) and non-mental state (involving reciprocal interaction without the intention to cause/act upon the other triangle’s mental state, e.g., following) interactions. Using Bayesian mixed effects models, we observed that haloperidol decreased accuracy in labelling both mental and non-mental state animations. Our secondary analyses suggest that dopamine modulates inference from mental and non-mental state animations via independent mechanisms, pointing towards 2 putative pathways underlying the dopaminergic modulation of mental state attribution: action representation and a shared mechanism supporting mentalising and emotion recognition. We conclude that dopaminergic pathways impact Theory of Mind, at least indirectly. Our results have implications for the neurochemical basis of sociocognitive difficulties in patients with dopamine dysfunctions and generate new hypotheses about the specific dopamine-mediated mechanisms underlying social cognition

Cross-cultural variation in experiences of acceptance, camouflaging and mental health difficulties in autism:A registered report

Recent findings suggest that stigma and camouflaging contribute to mental health difficulties for autistic individuals, however, this evidence is largely based on UK samples. While studies have shown cross-cultural differences in levels of autism-related stigma, it is unclear whether camouflaging and mental health difficulties vary across cultures. Hence, the current study had two aims: (1) to determine whether significant relationships between autism acceptance, camouflaging, and mental health difficulties replicate in a cross-cultural sample of autistic adults, and (2) to compare these variables across cultures. To fulfil these aims, 306 autistic adults from eight countries (Australia, Belgium, Canada, Japan, New Zealand, South Africa, the United Kingdom, and the United States) completed a series of online questionnaires. We found that external acceptance and personal acceptance were associated with lower levels of depression but not camouflaging or stress. Higher camouflaging was associated with elevated levels of depression, anxiety, and stress. Significant differences were found across countries in external acceptance, personal acceptance, depression, anxiety, and stress, even after controlling for relevant covariates. Levels of camouflaging also differed across countries however this effect became non-significant after controlling for the covariates. These findings have significant implications, identifying priority regions for anti-stigma interventions, and highlighting countries where greater support for mental health difficulties is needed

Point OutWords: protocol for a feasibility randomised controlled trial of a motor skills intervention to promote communicative development in non-verbal children with autism

Abstract: Background: Point OutWords is a caregiver-delivered, iPad-assisted intervention for non-verbal or minimally verbal children with autism. It aims to develop prerequisite skills for communication such as manual and oral motor skills, sequencing, and symbolic representation. This feasibility trial aims to determine the viability of evaluating the clinical efficacy of Point OutWords. Methodology: We aim to recruit 46 non-verbal or minimally verbal children with autism and their families, approximately 23 per arm. Children in the intervention group will use Point OutWords for half an hour, five times a week, for 8 weeks. Children in the control group will have equal caregiver-led contact time with the iPad using a selection of control apps (e.g. sensory apps, drawing apps). Communication, motor, and daily living skills are assessed at baseline and post-intervention. Parents will keep diaries during the intervention period and will take part in focus groups when the intervention is completed. Discussion: Point OutWords was developed in collaboration with children with autism and their caregivers, to provide an intervention for a subgroup of autism that has been historically underserved. As autism is a heterogeneous condition, it is unlikely that one style of intervention will address all aspects of its symptomatology; the motor skills approach of Point OutWords can complement other therapies that address core autistic symptoms of social cognition and communication more directly. The current feasibility trial can inform the selection of outcome measures and design for future full-scale randomised controlled trials of Point OutWords and of other early interventions in autism. Trial registration: ISRCTN, ISRCTN12808402. Prospectively registered on 12 March 2019

A MISSING-LINK IN THE SUPERNOVA-GRB CONNECTION: THE CASE OF SN 2012ap

Gamma Ray Bursts (GRBs) are characterized by ultra-relativistic outflows, while supernovae are generally characterized by non-relativistic ejecta. GRB afterglows decelerate rapidly usually within days, because their low-mass ejecta rapidly sweep up a comparatively larger mass of circumstellar material. However supernovae, with heavy ejecta, can be in nearly free expansion for centuries. Supernovae were thought to have non-relativistic outflows except for few relativistic ones accompanied by GRBs. This clear division was blurred by SN 2009bb, the first supernova with a relativistic outflow without an observed GRB. Yet the ejecta from SN 2009bb was baryon loaded, and in nearly-free expansion for a year, unlike GRBs. We report the first supernova discovered without a GRB, but with rapidly decelerating mildly relativistic ejecta, SN 2012ap. We discovered a bright and rapidly evolving radio counterpart driven by the circumstellar interaction of the relativistic ejecta. However, we did not find any coincident GRB with an isotropic fluence of more than a sixth of the fluence from GRB 980425. This shows for the first time that central engines in type Ic supernovae, even without an observed GRB, can produce both relativistic and rapidly decelerating outflows like GRBs.Comment: 8 pages, 5 figures, 1 table, accepted for publication in Ap

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe

Event-shape engineering for inclusive spectra and elliptic flow in Pb-Pb collisions at root(NN)-N-S=2.76 TeV

Peer reviewe

Elliptic flow of muons from heavy-flavour hadron decays at forward rapidity in Pb-Pb collisions at root s(NN)=2.76TeV

The elliptic flow, v(2), of muons from heavy-flavour hadron decays at forward rapidity (2.5 <y <4) is measured in Pb-Pb collisions at root s(NN)= 2.76TeVwith the ALICE detector at the LHC. The scalar product, two- and four-particle Q cumulants and Lee-Yang zeros methods are used. The dependence of the v(2) of muons from heavy-flavour hadron decays on the collision centrality, in the range 0-40%, and on transverse momentum, p(T), is studied in the interval 3 <p(T)<10 GeV/c. A positive v(2) is observed with the scalar product and two-particle Q cumulants in semi-central collisions (10-20% and 20-40% centrality classes) for the p(T) interval from 3 to about 5GeV/c with a significance larger than 3 sigma, based on the combination of statistical and systematic uncertainties. The v(2) magnitude tends to decrease towards more central collisions and with increasing pT. It becomes compatible with zero in the interval 6 <p(T)<10 GeV/c. The results are compared to models describing the interaction of heavy quarks and open heavy-flavour hadrons with the high-density medium formed in high-energy heavy-ion collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V.Peer reviewe