Atypical Language-Related Asymmetry Stratifies Male Individuals with Autism with and without Language Delay

Saturday, May 14, 2016: 11:30 AM-1:30 PM
Hall A (Baltimore Convention Center)
D. L. Floris1,2, M. C. Lai3,4,5, T. Auer6, M. V. Lombardo3,7, C. Ecker8, B. Chakrabarti1,9, S. J. Wheelwright1, E. Bullmore10,11,12,13, C. MRC AIMS14, D. G. Murphy8, S. Baron-Cohen3,10,13 and J. Suckling10,11,12,13, (1)Department of Psychiatry, Autism Research Centre, University of Cambridge, Cambridge, United Kingdom, (2)Department of Child and Adolescent Psychiatry, The Child Study Center at New York University Langone Medical Center, New York City, NY, (3)Autism Research Centre, University of Cambridge, Cambridge, United Kingdom, (4)Centre for Addiction and Mental Health, The Hospital for Sick Children, and Department of Psychiatry, University of Toronto, Toronto, ON, Canada, (5)Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan, (6)MRC Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom, (7)Department of Psychology and Center for Applied Neuroscience, University of Cyprus, Nikosia, Cyprus, (8)Sackler Institute for Translational Neurodevelopment, Department of Forensic and Neurodevelopmental Sciences,, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom, (9)School of Psychology & Clinical Language Sciences, University of Reading, Reading, United Kingdom, (10)Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom, (11)Department of Psychiatry, Brain Mapping Unit, University of Cambridge, Cambridge, United Kingdom, (12)National Institute of Health Research, Cambridge Biomedical Research Centre, Cambridge, United Kingdom, (13)Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom, (14)Autism Research Centre, University of Cambridge; the Institute of Psychiatry (IoP) at King’s College, London; Autism Research Group, University of Oxford, Cambridge, United Kingdom

Handedness and language are the most lateralized functions in the brain. Individuals with autism exhibit core deficits in language and auditory functions and show increased rates of non-right-handedness and atypical language specialization. Based on these observations, the prediction is that language-related measures of asymmetry should be sensitive to different developmental language profiles in individuals with autism.


No previous studies have examined lateralized differences in cortical language-related structures between language-delayed and non-language-delayed individuals with autism. Only one has looked at differences in handedness between these subgroups. Thus, we aimed to compare individuals with autism with and without language delay (LD) on language-related asymmetry measures including handedness and auditory and language cortical asymmetry.


Sample 1: Participants were recruited online from the Cambridge Autism Research Database. The sample comprised 445 males with autism (LD=52, no LD=393) and 2,372 control male adults without autism (18-60 years). Handedness was categorically classified as ‘right-handed’ or ‘non-right-handed’. A Chi-square-test compared the handedness categories across groups. 

Sample 2: Participants comprised 67 right-handed, high-functioning adult males with autism (LD: 26; no LD: 41) and 69 male adults aged 18-43 years. Autistic symptoms were assessed by the ADI-R and ADOS. Language was assessed by a phonological memory and a word-generativity task.

T1-weighted images were segmented, rigid-body registered and reflected across the midline using SPM8. All images were mapped onto a symmetrical study-specific DARTEL template. Laterality indices (LI) were defined as: 2*(right–left)/(right+left). Spatially-restricted voxel-wise analysis of LIs was conducted using two co-activation maps for the terms ‘language’ and ‘auditory’ from the online database NeuroSynth. To test the effect of LD, univariate ANCOVAs were conducted for the interaction between diagnosis and any significant cluster and language and symptom measures as dependent variables.


Sample1: A significant between-group difference in handedness was observed across the three groups of autism with LD, without LD, and controls (p<0.001). Individuals with autism with LD were more strongly non-right-handed than controls (Cohen’s d=0.404) and individuals with autism without LD showed an intermediate position (Cohen’s d=0.198).

Sample2: Voxel-wise analysis of LIs within the auditory ROI revealed significant reductions from typical leftward asymmetry in adults with autism with LD (cluster-level FDR-corrected q=0.015), but not in individuals with autism without LD who had a significant intermediate position based on a polynomial trend analysis (p<0.001). There were no significant differences for the language ROI. There was a trending interaction between diagnosis and the significant auditory cluster for social reciprocity symptoms (ADI-A) (p=0.066). Follow-up correlational analyses showed significance within individuals with autism with LD (r=0.373, p=0.036), but not in individuals with autism without LD (r=-0.092, p=0.289).


Increased non-right-handedness and reductions in leftward asymmetry of perisylvian regions were found in male adults with autism. These potentially constitute behavioural markers and biological underpinnings of LD associated with autism, and represent a putative cardinal neurophenotype of LD in autism. It still has to be established whether handedness also differentiates between different developmental language profiles in females with autism and whether atypical cortical asymmetries are more pronounced in language-delayed females with autism.