Subhadip Paul1,2, Aditi Arora2,3, Rashi Midha2,4, Dinh Vu5,6, Prasun K Roy2,7, Matthew K Belmonte8,9,10. 1. MIND Research Network, 1101 Yale Blvd NE, Albuquerque, NM, 87106, USA. 2. National Brain Research Centre, NH-8, Nainwal Mode, Manesar, 122051, India. 3. Centre for Cognitive Neuroscience, Universität Salzburg, Kapitelgasse 4-6, 5020, Salzburg, Austria. 4. National Institute of Mental Health and Neuro Sciences, Hosur Road, Bangalore, 560029, India. 5. Department of Psychology, University of Oslo, Harald Schjelderups hus, Forskningsveien 3A, 0373, Oslo, Norway. 6. Department of Psychology, Chaucer Bldg., Nottingham Trent University, Shakespeare Street, Nottingham, NG1 4FQ, UK. 7. School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, India. 8. National Brain Research Centre, NH-8, Nainwal Mode, Manesar, 122051, India. belmonte@mit.edu. 9. Department of Psychology, Chaucer Bldg., Nottingham Trent University, Shakespeare Street, Nottingham, NG1 4FQ, UK. belmonte@mit.edu. 10. The Com DEALL Trust, 224, 6th 'A' Main Road, near Specialist Hospital, 2nd Block, HRBR Layout, Bangalore, 560043, India. belmonte@mit.edu.
Abstract
BACKGROUND: Autism is characterised not only by impaired social cognitive 'empathising' but also by superior rule-based 'systemising'. These cognitive domains intertwine within the categorical diagnosis of autism, yet behavioural genetics suggest largely independent heritability, and separable brain mechanisms. We sought to determine whether quantitative behavioural measures of autistic traits are dimensionally associated with structural and functional brain network integrity, and whether brain bases of autistic traits vary independently across individuals. METHODS: Thirty right-handed neurotypical adults (12 females) were administered psychometric (Social Responsiveness Scale, Autism Spectrum Quotient and Systemising Quotient) and behavioural (Attention Network Test and theory-of-mind reaction time) measures of autistic traits, and structurally (diffusion tensor imaging) and functionally (500 s of 2 Hz eyes-closed resting fMRI) derived graph-theoretic measures of efficiency of information integration were computed throughout the brain and within subregions. RESULTS: Social impairment was positively associated with functional efficiency (r = .47, p = .006), globally and within temporo-parietal and prefrontal cortices. Delayed orienting of attention likewise was associated with greater functional efficiency (r = - .46, p = .0133). Systemising was positively associated with global structural efficiency (r = .38, p = 0.018), driven specifically by temporal pole; theory-of-mind reaction time was related to structural efficiency (r = - .40, p = 0.0153) within right supramarginal gyrus. LIMITATIONS: Interpretation of these relationships is complicated by the many senses of the term 'connectivity', including functional, structural and computational; by the approximation inherent in group functional anatomical parcellations when confronted with individual variation in functional anatomy; and by the validity, sensitivity and specificity of the several survey and experimental behavioural measures applied as correlates of brain structure and function. CONCLUSIONS: Functional connectivities highlight distributed networks associated with domain-general properties such as attentional orienting and social cognition broadly, associating more impaired behaviour with more efficient brain networks that may reflect heightened feedforward information flow subserving autistic strengths and deficits alike. Structural connectivity results highlight specific anatomical nodes of convergence, reflecting cognitive and neuroanatomical independence of systemising and theory-of-mind. In addition, this work shows that individual differences in theory-of-mind related to brain structure can be measured behaviourally, and offers neuroanatomical evidence to pin down the slippery construct of 'systemising' as the capacity to construct invariant contextual associations.
BACKGROUND:Autism is characterised not only by impaired social cognitive 'empathising' but also by superior rule-based 'systemising'. These cognitive domains intertwine within the categorical diagnosis of autism, yet behavioural genetics suggest largely independent heritability, and separable brain mechanisms. We sought to determine whether quantitative behavioural measures of autistic traits are dimensionally associated with structural and functional brain network integrity, and whether brain bases of autistic traits vary independently across individuals. METHODS: Thirty right-handed neurotypical adults (12 females) were administered psychometric (Social Responsiveness Scale, Autism Spectrum Quotient and Systemising Quotient) and behavioural (Attention Network Test and theory-of-mind reaction time) measures of autistic traits, and structurally (diffusion tensor imaging) and functionally (500 s of 2 Hz eyes-closed resting fMRI) derived graph-theoretic measures of efficiency of information integration were computed throughout the brain and within subregions. RESULTS: Social impairment was positively associated with functional efficiency (r = .47, p = .006), globally and within temporo-parietal and prefrontal cortices. Delayed orienting of attention likewise was associated with greater functional efficiency (r = - .46, p = .0133). Systemising was positively associated with global structural efficiency (r = .38, p = 0.018), driven specifically by temporal pole; theory-of-mind reaction time was related to structural efficiency (r = - .40, p = 0.0153) within right supramarginal gyrus. LIMITATIONS: Interpretation of these relationships is complicated by the many senses of the term 'connectivity', including functional, structural and computational; by the approximation inherent in group functional anatomical parcellations when confronted with individual variation in functional anatomy; and by the validity, sensitivity and specificity of the several survey and experimental behavioural measures applied as correlates of brain structure and function. CONCLUSIONS: Functional connectivities highlight distributed networks associated with domain-general properties such as attentional orienting and social cognition broadly, associating more impaired behaviour with more efficient brain networks that may reflect heightened feedforward information flow subserving autistic strengths and deficits alike. Structural connectivity results highlight specific anatomical nodes of convergence, reflecting cognitive and neuroanatomical independence of systemising and theory-of-mind. In addition, this work shows that individual differences in theory-of-mind related to brain structure can be measured behaviourally, and offers neuroanatomical evidence to pin down the slippery construct of 'systemising' as the capacity to construct invariant contextual associations.
Authors: Simon Baron-Cohen; Jennifer Richler; Dheraj Bisarya; Nhishanth Gurunathan; Sally Wheelwright Journal: Philos Trans R Soc Lond B Biol Sci Date: 2003-02-28 Impact factor: 6.237