Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers

Abstract Background The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. Methods Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). Results The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. Limitations The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. Conclusions Biological motion preference elicits small-to-medium-sized case–control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.

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Imaging of depressive disorders

New Oxford Textbook of Psychiatry ◽

10.1093/med/9780198713005.003.0076 ◽

2020 ◽

pp. 797-806

Author(s):

Guy M. Goodwin ◽

Michael Browning

Keyword(s):

Depressive Disorders ◽

Case Control ◽

Structure And Function ◽

Small Sample ◽

Case Control Studies ◽

Brain Structure And Function ◽

Small Sample Sizes ◽

And Function ◽

Study Designs ◽

And Control

Neuroimaging techniques have been used extensively to compare brain structure and function between patients with, or at risk of, depression and control subjects. The goal of this work has largely been to identify pathophysiological processes in depression. However, progress in this field has been limited by the heterogeneity of patient populations, the use of small sample sizes, and an overreliance on case-control studies. These limitations have increasingly been acknowledged with recent work collecting much larger samples and employing a variety of study designs, including those able to stratify patient populations. This chapter reviews imaging studies in depression, highlighting both outstanding questions and promising recent findings.

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WMW-A: Rank-based two-sample independent test for small sample sizes through an auxiliary sample

10.1101/2021.06.24.449844 ◽

2021 ◽

Author(s):

Yin Guo ◽

Limin Li

Keyword(s):

Gene Expression ◽

Case Control ◽

Test Methods ◽

Small Sample ◽

Sample Problem ◽

Auxiliary Data ◽

Independent Test ◽

Small Sample Problem ◽

Small Sample Sizes ◽

And Control

Two-sample independent test methods are widely used in case-control studies to identify significant changes or differences, for example, to identify key pathogenic genes by comparing the gene expression levels in normal and disease cells. However, due to the high cost of data collection or labelling, many studies face the small sample problem, for which the traditional two-sample test methods often lose power. We propose a novel rank-based nonparametric test method WMW-A for small sample problem by introducing a three-sample statistic through another auxiliary sample. By combining the case, control and auxiliary samples together, we construct a three-sample WMW-A statistic based on the gap between the average ranks of the case and control samples in the combined samples. By assuming that the auxiliary sample follows a mixed distribution of the case and control populations, we analyze the theoretical properties of the WMW-A statistic and approximate the theoretical power. The extensive simulation experiments and real applications on microarray gene expression data sets show the WMW-A test could significantly improve the test power for two-sample problem with small sample sizes, by either available unlabelled auxiliary data or generated auxiliary data.

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A Connectome-Wide Functional Signature of Trait Anger

Clinical Psychological Science ◽

10.1177/21677026211030240 ◽

2021 ◽

pp. 216770262110302

Author(s):

M. Justin Kim ◽

Maxwell L. Elliott ◽

Annchen R. Knodt ◽

Ahmad R. Hariri

Keyword(s):

Functional Connectivity ◽

Visual Information ◽

Past Research ◽

Brain Regions ◽

Small Sample ◽

Trait Anger ◽

Frontal Pole ◽

Brain Correlates ◽

Small Sample Sizes ◽

The Right

Past research on the brain correlates of trait anger has been limited by small sample sizes, a focus on relatively few regions of interest, and poor test–retest reliability of functional brain measures. To address these limitations, we conducted a data-driven analysis of variability in connectome-wide functional connectivity in a sample of 1,048 young adult volunteers. Multidimensional matrix regression analysis showed that self-reported trait anger maps onto variability in the whole-brain functional connectivity patterns of three brain regions that serve action-related functions: bilateral supplementary motor areas and the right lateral frontal pole. We then demonstrate that trait anger modulates the functional connectivity of these regions with canonical brain networks supporting somatomotor, affective, self-referential, and visual information processes. Our findings offer novel neuroimaging evidence for interpreting trait anger as a greater propensity to provoked action, which supports ongoing efforts to understand its utility as a potential transdiagnostic marker for disordered states characterized by aggressive behavior.

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Perception of biological motion in autism spectrum disorders

Neuropsychologia ◽

10.1016/j.neuropsychologia.2007.12.025 ◽

2008 ◽

Vol 46 (5) ◽

pp. 1480-1494 ◽

Cited By ~ 133

Author(s):

Christine M. Freitag ◽

Carsten Konrad ◽

Melanie Häberlen ◽

Christina Kleser ◽

Alexander von Gontard ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Biological Motion ◽

Autism Spectrum ◽

Spectrum Disorders ◽

Perception Of Biological Motion

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Individual Observer Differences in the Use of Form and Motion to Perceive the Actor’s Sex in Biological Motion Displays

Perceptual and Motor Skills ◽

10.1177/00315125211052923 ◽

2021 ◽

pp. 003151252110529

Author(s):

Eric Hiris ◽

Sean Conway ◽

William McLoughlin ◽

Gaokhia Yang

Keyword(s):

Biological Motion ◽

Autism Spectrum ◽

Autism Spectrum Quotient ◽

Group Level ◽

Motion Cues ◽

Motion Imagery ◽

Adult Participants ◽

Participant Characteristics ◽

Perception Of Biological Motion ◽

Form Information

Recent research has shown that the perception of biological motion may be influenced by aspects of the observer’s personality. In this study, we sought to determine how participant characteristics (including demographics, response inhibition, autism spectrum quotient, empathy, social anxiety, and motion imagery) might influence the use of form and motion to identify the actor’s sex in biological motion displays. We varied the degree of form and motion in biological motion displays and correlated 76 young adult participants’ performances for identifying the actor’s sex in these varied conditions with their individual differences on variables of interest. Differences in the separate use of form and motion cues were predictive of participant performance generally, with use of form most predictive of performance. Female participants relied primarily on form information, while male participants relied primarily on motion information. Participants less able to visualize movement tended to be better at using form information in the biological motion task. Overall, our findings suggest that similar group level performances across participants in identifying the sex of the actor in a biological motion task may result from quite different individual processing.

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Sample Size Determination and Optimal Design of Simple Pretest-Posttest Experimental Designs: Introduction, Software, and Illustrations

10.35542/osf.io/k5ey8 ◽

2021 ◽

Author(s):

Metin Bulus

Keyword(s):

Optimal Design ◽

Sample Size ◽

Small Sample ◽

Experimental Designs ◽

Sample Size Determination ◽

Size Determination ◽

Sample Sizes ◽

Control Groups ◽

Small Sample Sizes ◽

And Control

A recent systematic review of experimental studies conducted in Turkey between 2010 and 2020 reported that small sample sizes had been a significant drawback (Bulus and Koyuncu, 2021). A small chunk of the studies were small-scale true experiments (subjects randomized into the treatment and control groups). The remaining studies consisted of quasi-experiments (subjects in treatment and control groups were matched on pretest or other covariates) and weak experiments (neither randomized nor matched but had the control group). They had an average sample size below 70 for different domains and outcomes. These small sample sizes imply a strong (and perhaps erroneous) assumption about the minimum relevant effect size (MRES) of intervention before an experiment is conducted; that is, a standardized intervention effect of Cohen’s d < 0.50 is not relevant to education policy or practice. Thus, an introduction to sample size determination for pretest-posttest simple experimental designs is warranted. This study describes nuts and bolts of sample size determination, derives expressions for optimal design under differential cost per treatment and control units, provide convenient tables to guide sample size decisions for MRES values between 0.20 ≤ Cohen’s d ≤ 0.50, and describe the relevant software along with illustrations.

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The social brain in female autism: a structural imaging study of twins

Social Cognitive and Affective Neuroscience ◽

10.1093/scan/nsaa064 ◽

2020 ◽

Vol 15 (4) ◽

pp. 423-436

Author(s):

Élodie Cauvet ◽

Annelies van’t Westeinde ◽

Roberto Toro ◽

Ralf Kuja-Halkola ◽

Janina Neufeld ◽

...

Keyword(s):

Sex Differences ◽

Social Cognition ◽

Brain Structure ◽

Imaging Study ◽

Autistic Traits ◽

Brain Regions ◽

Autism Spectrum ◽

Social Brain ◽

Twin Design ◽

The Social

Abstract A female advantage in social cognition (SoC) might contribute to women’s underrepresentation in autism spectrum disorder (ASD). The latter could be underpinned by sex differences in social brain structure. This study investigated the relationship between structural social brain networks and SoC in females and males in relation to ASD and autistic traits in twins. We used a co-twin design in 77 twin pairs (39 female) aged 12.5 to 31.0 years. Twin pairs were discordant or concordant for ASD or autistic traits, discordant or concordant for other neurodevelopmental disorders or concordant for neurotypical development. They underwent structural magnetic resonance imaging and were assessed for SoC using the naturalistic Movie for the Assessment of Social Cognition. Autistic traits predicted reduced SoC capacities predominantly in male twins, despite a comparable extent of autistic traits in each sex, although the association between SoC and autistic traits did not differ significantly between the sexes. Consistently, within-pair associations between SoC and social brain structure revealed that lower SoC ability was associated with increased cortical thickness of several brain regions, particularly in males. Our findings confirm the notion that sex differences in SoC in association with ASD are underpinned by sex differences in brain structure.

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Distinguishing autism from co-existing conditions: a behavioural profiling investigation

Advances in Autism ◽

10.1108/aia-09-2015-0018 ◽

2016 ◽

Vol 2 (1) ◽

pp. 41-54

Author(s):

Ashleigh Saunders ◽

Karen E. Waldie

Keyword(s):

Statistical Power ◽

Psychiatric Comorbidity ◽

Adaptive Functioning ◽

Autism Spectrum ◽

Small Sample ◽

Comorbid Conditions ◽

Sample Sizes ◽

Content Type ◽

Small Sample Sizes ◽

Comorbid Adhd

Purpose – Autism spectrum disorder (ASD) is a lifelong neurodevelopmental condition for which there is no known cure. The rate of psychiatric comorbidity in autism is extremely high, which raises questions about the nature of the co-occurring symptoms. It is unclear whether these additional conditions are true comorbid conditions, or can simply be accounted for through the ASD diagnosis. The paper aims to discuss this issue. Design/methodology/approach – A number of questionnaires and a computer-based task were used in the current study. The authors asked the participants about symptoms of ASD, attention deficit hyperactivity disorder (ADHD) and anxiety, as well as overall adaptive functioning. Findings – The results demonstrate that each condition, in its pure form, can be clearly differentiated from one another (and from neurotypical controls). Further analyses revealed that when ASD occurs together with anxiety, anxiety appears to be a separate condition. In contrast, there is no clear behavioural profile for when ASD and ADHD co-occur. Research limitations/implications – First, due to small sample sizes, some analyses performed were targeted to specific groups (i.e. comparing ADHD, ASD to comorbid ADHD+ASD). Larger sample sizes would have given the statistical power to perform a full scale comparative analysis of all experimental groups when split by their comorbid conditions. Second, males were over-represented in the ASD group and females were over-represented in the anxiety group, due to the uneven gender balance in the prevalence of these conditions. Lastly, the main profiling techniques used were questionnaires. Clinical interviews would have been preferable, as they give a more objective account of behavioural difficulties. Practical implications – The rate of psychiatric comorbidity in autism is extremely high, which raises questions about the nature of the co-occurring symptoms. It is unclear whether these additional conditions are true comorbid conditions, or can simply be accounted for through the ASD diagnosis. Social implications – This information will be important, not only to healthcare practitioners when administering a diagnosis, but also to therapists who need to apply evidence-based treatment to comorbid and stand-alone conditions. Originality/value – This study is the first to investigate the nature of co-existing conditions in ASD in a New Zealand population.

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Distinct neural mechanisms of social orienting and mentalizing revealed by independent measures of neural and eye movement typicality

10.1101/726356 ◽

2019 ◽

Author(s):

Michal Ramot ◽

Catherine Walsh ◽

Gabrielle E. Reimann ◽

Alex Martin

Keyword(s):

Eye Movement ◽

Brain Regions ◽

Autism Spectrum ◽

Extensive Study ◽

Neural Systems ◽

Typically Developing ◽

Social Brain ◽

Social Orienting ◽

The Social ◽

Interacting Systems

AbstractExtensive study of typically developing individuals and those on the autism spectrum has identified a large number of brain regions associated with our ability to navigate the social world. Although it is widely appreciated that this so-called ‘social brain’ is composed of distinct, interacting systems, these component parts have yet to be clearly elucidated. Here we used measures of eye movement and neural typicality – based on the degree to which subjects deviated from the norm – while typically developing (N = 62) and individuals with autism (N = 36) watched a large battery of movies depicting social interactions. Our findings provide clear evidence for distinct, but overlapping, neural systems underpinning two major components of the ‘social brain’, social orienting and inferring the mental state of others.

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Brain Responses Underlying Anthropomorphism, Agency, and Social Attribution in Autism Spectrum Disorder

The Open Neuroimaging Journal ◽

10.2174/1874440001812010016 ◽

2018 ◽

Vol 12 (1) ◽

pp. 16-29 ◽

Cited By ~ 1

Author(s):

Carla J. Ammons ◽

Constance F. Doss ◽

David Bala ◽

Rajesh K. Kana

Keyword(s):

Autism Spectrum Disorder ◽

Social Movement ◽

Mental States ◽

Brain Regions ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Social Brain ◽

Social Attribution ◽

Brain Responses ◽

Fmri Study

Background:Theory of Mind (ToM), the ability to attribute mental states to oneself and others, is frequently impaired in Autism Spectrum Disorder (ASD) and may result from altered activation of social brain regions. Conversely, Typically Developing (TD) individuals overextend ToM and show a strong tendency to anthropomorphize and interpret biological motion in the environment. Less is known about how the degree of anthropomorphism influences intentional attribution and engagement of the social brain in ASD.Objective:This fMRI study examines the extent of anthropomorphism, its role in social attribution, and the underlying neural responses in ASD and TD using a series of human stick figures and geometrical shapes.Methods:14 ASD and 14 TD adults watched videos of stick figures and triangles interacting in random or socially meaningful ways while in an fMRI scanner. In addition, they completed out-of-scanner measures of ToM skill and real-world social deficits. Whole brain statistical analysis was performed for regression and within and between group comparisons of all conditions using SPM12’s implementation of the general linear model.Results:ToM network regions were activated in response to social movement and human-like characters in ASD and TD. In addition, greater ToM ability was associated with increased TPJ and MPFC activity while watching stick figures; whereas more severe social symptoms were associated with reduced right TPJ activation in response to social movement.Conclusion:These results suggest that degree of anthropomorphism does not differentially affect social attribution in ASD and highlights the importance of TPJ in ToM and social attribution.

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