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‘Reading the Mind in the Eyes’: an fMRI study of adolescents with autism and their siblings

Published online by Cambridge University Press:  26 February 2014

R. J. Holt ,
L. R. Chura ,
M.-C. Lai ,
J. Suckling ,
E. von dem Hagen ,
A. J. Calder ,
E. T. Bullmore ,
S. Baron-Cohen  and
M. D. Spencer
R. J. Holt*
Affiliation:
Autism Research Centre, Department of Psychiatry, University of Cambridge, UK Brain Mapping Unit, Department of Psychiatry, University of Cambridge, UK
L. R. Chura
Affiliation:
Autism Research Centre, Department of Psychiatry, University of Cambridge, UK
M.-C. Lai
Affiliation:
Autism Research Centre, Department of Psychiatry, University of Cambridge, UK Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan
J. Suckling
Affiliation:
Brain Mapping Unit, Department of Psychiatry, University of Cambridge, UK Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK
E. von dem Hagen
Affiliation:
MRC Cognition and Brain Sciences Unit, Cambridge, UK
A. J. Calder
Affiliation:
MRC Cognition and Brain Sciences Unit, Cambridge, UK
E. T. Bullmore
Affiliation:
Brain Mapping Unit, Department of Psychiatry, University of Cambridge, UK Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK
S. Baron-Cohen
Affiliation:
Autism Research Centre, Department of Psychiatry, University of Cambridge, UK Cambridge and Peterborough NHS Foundation Trust, Cambridge, UK
M. D. Spencer
Affiliation:
Autism Research Centre, Department of Psychiatry, University of Cambridge, UK
*
* Address for correspondence: Dr R. J. Holt, Autism Research Centre, Cambridge University, Douglas House, 18b Trumpington Road, Cambridge CB2 8AH, UK. (Email: rh465@cam.ac.uk)
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Abstract

Background.

Mentalizing deficits are a hallmark of the autism spectrum condition (ASC) and a potential endophenotype for atypical social cognition in ASC. Differences in performance and neural activation on the ‘Reading the Mind in the Eyes’ task (the Eyes task) have been identified in individuals with ASC in previous studies.

Method.

Performance on the Eyes task along with the associated neural activation was examined in adolescents with ASC (n = 50), their unaffected siblings (n = 40) and typically developing controls (n = 40). Based on prior literature that males and females with ASC display different cognitive and associated neural characteristics, analyses were stratified by sex. Three strategies were applied to test for endophenotypes at the level of neural activation: (1) identifying and locating conjunctions of ASC–control and sibling–control differences; (2) examining whether the sibling group is comparable to the ASC or intermediate between the ASC and control groups; and (3) examining spatial overlaps between ASC–control and sibling–control differences across multiple thresholds.

Results.

Impaired behavioural performance on the Eyes task was observed in males with ASC compared to controls, but only at trend level in females; and no difference in performance was identified between sibling and same-sex control groups in both sexes. Neural activation showed a substantial endophenotype effect in the female groups but this was only modest in the male groups.

Conclusions.

Behavioural impairment on complex emotion recognition associated with mental state attribution is a phenotypic, rather than an endophenotypic, marker of ASC. However, the neural response during the Eyes task is a potential endophenotypic marker for ASC, particularly in females.

Keywords

Autismemotion recognitionendophenotypesfMRI
Type
Original Articles
Information
Psychological Medicine , Volume 44 , Issue 15 , November 2014 , pp. 3215 - 3227
Copyright
Copyright © Cambridge University Press 2014 

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References

Adams, RB, Rule, NO, Franklin, RG, Wang, E, Stevenson, MT, Yoshihawa, S, Nomura, M, Sato, W, Kveraga, K, Ambady, N (2010). Cross-cultural reading the mind in the eyes: an fMRI investigation. Journal of Cognitive Neuroscience 22, 97–108.Google Scholar
Baron-Cohen, S, Hammer, J (1997). Parents of children with Asperger syndrome: what is the cognitive phenotype? Journal of Cognitive Neuroscience 9, 548–554.Google Scholar
Baron-Cohen, S, Jolliffe, T, Mortimore, C, Robertson, M (1997). Another advanced test of theory of mind: evidence from very high functioning adults with autism or Asperger syndrome. Journal of Child Psychology and Psychiatry 38, 813–822.Google Scholar
Baron-Cohen, S, Knickmeyer, RC, Belmonte, MK (2005). Sex differences in the brain: implications for explaining autism. Science 310, 819–823.CrossRefGoogle ScholarPubMed
Baron-Cohen, S, Lombardo, MV, Auyeung, B, Ashwin, E, Chakrabarti, B, Knickmeyer, R (2011). Why are autism spectrum conditions more prevalent in males? PLoS Biology 9, e1001081.Google Scholar
Baron-Cohen, S, Ring, H, Chitnis, X, Wheelwright, S, Gregory, L, Williams, S, Brammer, M, Bullmore, E (2006). fMRI of parents of children with Asperger syndrome: a pilot study. Brain and Cognition 61, 122–130.Google Scholar
Baron-Cohen, S, Ring, HA, Moriarty, J, Schmitz, B, Costa, D, Ell, P (1994). Recognition of mental state terms. Clinical findings in children with autism and a functional neuroimaging study of normal adults. British Journal of Psychiatry 165, 640–649.Google Scholar
Baron-Cohen, S, Ring, HA, Wheelwright, S, Bullmore, ET, Brammer, MJ, Simmons, A, Williams, SC (1999). Social intelligence in the normal and autistic brain: an fMRI study. European Journal of Neuroscience 11, 1891–1898.Google Scholar
Baron-Cohen, S, Wheelwright, S, Hill, J, Raste, Y, Plumb, I (2001 a). The ‘Reading the Mind in the Eyes’ Test revised version: a study with normal adults, and adults with Asperger syndrome or high-functioning autism. Journal of Child Psychology and Psychiatry 42, 241–251.Google Scholar
Baron-Cohen, S, Wheelwright, S, Scahill, V, Lawson, J, Spong, A (2001 b). Are intuitive physics and intuitive psychology independent? A test with children with Asperger syndrome. Journal of Developmental and Learning Disorders 5, 47–78.Google Scholar
Beacher, FD, Minati, L, Baron-Cohen, S, Lombardo, MV, Lai, MC, Gray, MA, Harrison, NA, Crichley, HD (2012 a). Autism attenuates sex differences in brain structure: a combined voxel-based morphometry and diffusion tensor imaging study. American Journal of Neuroradiology 33, 83–89.Google Scholar
Beacher, FD, Radulescu, E, Minati, L, Baron-Cohen, S, Lombardo, MV, Lai, MC, Walker, A, Howard, D, Gray, MA, Harrison, NA, Crichley, HD (2012 b). Sex differences and autism: brain function during verbal fluency and mental rotation. PLoS One 7, e38355.Google Scholar
Bloss, CS, Courchesne, E (2007). MRI neuroanatomy in young girls with autism: a preliminary study. Journal of the American Academy of Child and Adolescent Psychiatry 46, 515–523.Google Scholar
Brothers, L (1990). The social brain: a project for integrating primate behaviour and neurophysiology in a new domain. Concepts in Neuroscience 1, 27–51.Google Scholar
Chumbley, JR, Friston, KJ (2009). False discovery rate revisited: FDR and topological inference using Gaussian random fields. NeuroImage 44, 62–70.Google Scholar
Di Martino, A, Ross, K, Uddin, LQ, Sklar, AB, Castellanos, FX, Milham, MP (2009). Functional brain imaging correlates of social and nonsocial processes in autism spectrum disorders: an activation likelihood estimation meta-analysis. Biological Psychiatry 65, 63–74.Google Scholar
Dorris, L, Espie, CA, Knott, F, Salt, J (2004). Mind-reading difficulties in the siblings of people with Asperger's syndrome: evidence for a genetic influence in the abnormal development of a specific cognitive domain. Journal of Child Psychology and Psychiatry 45, 412–418.Google Scholar
Evans, AC, Marrett, S, Neelin, P, Collins, L, Worsley, K, Dai, W, Milot, S, Meyer, E, Bub, D (1992). Anatomical mapping of functional activation in stereotactic coordinate space. NeuroImage 1, 43–53.CrossRefGoogle ScholarPubMed
Floris, DL, Chura, LR, Holt, RJ, Suckling, J, Bullmore, ET, Baron-Cohen, S, Spencer, MD (2013). Psychological correlates of handedness and corpus callosum asymmetry in autism: the left hemisphere dysfunction theory revisited. Journal of Autism and Developmental Disorders 43, 1758–1772.Google Scholar
Frith, U, Frith, CD (2003). Development and neurophysiology of mentalizing. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 358, 459–473.Google Scholar
Goken, M, Bora, E, Erermis, S, Kesikci, H, Aydin, C (2009). Theory of mind and verbal working memory deficits in parents of autistic children. Psychiatry Research 166, 46–53.Google Scholar
Gottesman, II, Gould, TD (2003). The endophenotype concept in psychiatry: etymology and strategic interventions. American Journal of Psychiatry 160, 636–645.Google Scholar
Greimel, E, Schulte-Ruther, M, Kircher, T, Kamp-Becker, I, Remschmidt, H, Fink, GR, Herpertz-Dahlmann, B, Konrad, K (2010). Neural mechanisms of empathy in adolescents with autism spectrum disorder and their fathers. NeuroImage 49, 1055–1065.Google Scholar
Huang, J, Zhu, Z, Zhang, JX, Wu, M, Chen, HC, Wang, S (2012). The role of left inferior frontal gyrus in explicit and implicit semantic processing. Brain Research 1440, 56–64.Google Scholar
Kaiser, MD, Hudac, CM, Shultz, S, Lee, SM, Cheung, C, Berken, AM, Deen, B, Pitskel, NB, Sugrue, DR, Voos, AC, Saulnier, CA, Ventola, P, Wolf, JM, Klin, A, Vander Wyk, BC, Pelphrey, KA (2010). Neural signatures of autism. Proceedings of the National Academy of Sciences USA 107, 21223–21228.Google Scholar
Kaland, N, Callesen, K, Moller-Nielsen, A, Mortensen, EL, Smith, L (2008). Performance of children and adolescents with Asperger syndrome or high-functioning autism on advanced theory of mind tasks. Journal of Autism and Developmental Disorders 38, 1112–1123.CrossRefGoogle ScholarPubMed
Kirkovski, M, Enticott, PG, Fitzgerald, PB (2013). A review of the role of female gender in autism spectrum disorders. Journal of Autism and Developmental Disorders 43, 2584–2603.Google Scholar
Lai, MC, Lombardo, MV, Baron-Cohen, S (2013 a). Autism. Lancet. Published online: 25 September 2013 . doi:10.1016/S0140-6736(13)61539-1.Google ScholarPubMed
Lai, MC, Lombardo, MV, Chakrabarti, B, Baron-Cohen, S (2013 b). Subgrouping the autism ‘spectrum’: reflections on DSM-5. PLoS Biology 11, e1001544.Google Scholar
Lai, MC, Lombardo, MV, Ruigrok, AN, Chakrabarti, B, Wheelwright, SJ, Auyeung, B, Allison, C;MRC AIMS Consortium, Baron-Cohen, S (2012). Cognition in males and females with autism: similarities and differences. PLoS One 7, e47198.Google Scholar
Lai, MC, Lombardo, MV, Suckling, J, Ruigrok, AN, Chakrabarti, B, Ecker, C, Deoni, SC, Craig, MC, Murphy, DG, Bullmore, ET; MRC AIMS Consortium, Baron-Cohen, S (2013 c). Biological sex affects the neurobiology of autism. Brain 136, 2799–2815.CrossRefGoogle ScholarPubMed
Le Couteur, A, Lord, C, Rutter, M (2003). Autism Diagnostic Interview – Revised. Western Psychological Services: Los Angeles, CA.Google Scholar
Lombardo, MV, Ashwin, E, Auyeung, B, Chakrabarti, B, Taylor, K, Hackett, G, Bullmore, ET, Baron-Cohen, S (2012). Fetal testosterone influences sexually dimorphic gray matter in the human brain. Journal of Neuroscience 32, 674–680.Google Scholar
Lord, C, Risi, S, Lambrecht, L (2001). The Autism Diagnostic Observational Schedule – Generic. Western Psychological Services: Los Angeles, CA.Google Scholar
Lord, C, Schopler, E (1985). Differences in sex ratios in autism as a function of measured intelligence. Journal of Autism and Developmental Disorders 15, 185–193.Google Scholar
Lord, C, Schopler, E, Revicki, D (1982). Sex differences in autism. Journal of Autism and Developmental Disorders 12, 317–330.CrossRefGoogle ScholarPubMed
Losh, M, Adolphs, R, Poe, MD, Couture, S, Penn, D, Baranek, GT, Piven, J (2009). Neuropsychological profile of autism and the broad autism phenotype. Archives of General Psychiatry 66, 518–526.CrossRefGoogle ScholarPubMed
Losh, M, Piven, J (2007). Social-cognition and the broad autism phenotype: identifying genetically meaningful phenotypes. Journal of Child Psychology and Psychiatry 48, 105–112.CrossRefGoogle ScholarPubMed
Nichols, T, Brett, M, Anderson, J, Wager, T, Poline, JB (2005). Valid conjunction inference with the minimum static. NeuroImage 25, 653–660.Google Scholar
Nordahl, CW, Lange, N, DD, Li, Barnett, LA, Lee, A, Buonocore, MH, Simon, TJ, Rogers, S, Ozonoff, S, Amaral, DG (2011). Proceedings of the National Academy of Sciences USA 108, 20195–10200.Google Scholar
Peterson, E, Miller, SF (2012). The Eyes Test as a measure of individual differences: how much of the variance reflects verbal IQ? Frontiers in Psychology 3, 220.Google Scholar
Philip, RC, Dauvermann, MR, Whalley, HC, Baynham, K, Lawrie, SM, Stanfield, AC (2012). A systematic review and meta-analysis of the fMRI investigation of autism spectrum disorders. Neuroscience and Biobehavioral Reviews 36, 901–942.CrossRefGoogle ScholarPubMed
Pironti, VA, Lai, MC, Müller, U, Dodds, CM, Suckling, J, Bullmore, ET, Sahakian, BJ (2013). Neuroanatomical abnormalities and cognitive impairments are shared by adults with attention-deficit/hyperactivity disorder and their unaffected first degree relatives. Biological Psychiatry. Published online: 5 October 2013 . doi:10.1016/j.biopsych.2013.09.025.Google Scholar
Piven, J, Palmer, P, Jacobi, D, Childress, D, Arndt, S (1997). Broader autism phenotype: evidence from a family history study of multiple-incidence autism families. American Journal of Psychiatry 154, 185–190.Google Scholar
Rutter, M, Bailey, A, Berument, SK, Lord, C, Pickles, A (2003). Social Communication Scale (SCQ). Western Psychological Services: Los Angeles, CA.Google Scholar
Spencer, MD, Chura, LR, Holt, RJ, Suckling, J, Calder, AJ, Bullmore, ET, Baron-Cohen, S (2012 a). Failure to deactivate the default mode network indicates a possible endophenotype of autism. Molecular Autism 3, 15.Google Scholar
Spencer, MD, Holt, RJ, Chura, LR, Calder, AJ, Suckling, J, Bullmore, ET, Baron-Cohen, S (2012 b). Atypical activation during the Embedded Figures Task as a functional magnetic resonance imaging endophenotype of autism. Brain 135, 3469–3480.Google Scholar
Spencer, MD, Holt, RJ, Chura, LR, Suckling, J, Calder, AJ, Bullmore, ET, Baron-Cohen, S (2011). A novel functional brain imaging endophenotype of autism: the neural response to facial expression of emotion. Translational Psychiatry 1, e19.Google Scholar
Sucksmith, E, Roth, I, Hoekstra, RA (2011). Autistic traits below the clinical threshold: re-examining the broader autism phenotype in the 21st century. Neuropsychology Review 21, 360–389.Google Scholar
Tsai, L, Beisler, J (1983). The development of sex differences in infantile autism. British Journal of Psychiatry 142, 373–378.Google Scholar
Tsai, L, Stewart, MA, August, G (1981). Implication of sex differences in the familial transmission of infantile autism. Journal of Autism and Developmental Disorders 11, 165–173.CrossRefGoogle ScholarPubMed
Viding, E, Blakemore, S-J (2007). Endophenotype approach to developmental psychopathology: implications for autism research. Behavior Genetics 37, 51–60.Google Scholar
Wechsler, D (1999). Wechsler Abbreviated Scale of Intelligence. The Psychological Corporation: London.Google Scholar
Werling, DM, Geschwind, DH (2013 a). Sex differences in autism spectrum disorders. Current Opinion in Neurology 26, 146–153.CrossRefGoogle ScholarPubMed
Werling, DM, Geschwind, DH (2013 b). Understanding sex bias in autism spectrum disorder. Proceedings of the National Academy of Sciences USA 110, 4868–4869.CrossRefGoogle ScholarPubMed
Wheelwright, S, Auyeung, B, Alison, C, Baron-Cohen, S (2010). Defining the broader, medium and narrow autism phenotype among parents using the Autism Spectrum Quotient (AQ). Molecular Autism 1, 10.Google Scholar
Yoder, P, Stone, WL, Walden, T, Malesa, E (2009). Predicting social impairment and ASD diagnosis in younger siblings of children with autism spectrum disorder. Journal of Autism and Developmental Disorders 39, 1381–1391.CrossRefGoogle ScholarPubMed