White Matter Microstructure of the Human Mirror Neuron System is Related to Symptom Severity in Adults with Autism
Mirror neuron system (MNS) dysfunctions might underlie deficits in autism spectrum disorders (ASD). Diffusion tensor imaging based probabilistic tractography was conducted in 15 adult ASD patients and 13 matched, healthy controls. Fractional anisotropy (FA) was quantified to assess group differences in tract-related white matter microstructure of both the classical MNS route (mediating “emulation”) and the alternative temporo-frontal route (mediating “mimicry”). Multiple linear regression was used to investigate structure–function relationships between MNS connections and ASD symptom severity. There were no significant group differences in tract-related FA indicating an intact classical MNS in ASD. Direct temporo-frontal connections could not be reconstructed challengeing the concept of multiple routes for imitation. Tract-related FA of right-hemispheric parieto-frontal connections was negatively related to autism symptom severity.
KeywordsAutism spectrum disorders Diffusion tensor imaging Fiber tracking Imitation Mirror neuron system
We would like to thank the patients for their participation in the study.
This study was supported by the Else Kröner-Fresenius-Stiftung (2011_A37; AM), by the Deutsche Forschungsgemeinschaft (DFG; SFB 936/A3/C5, A.M., A.K.E.) and by the European Union (EU, “socSMCs” - H2020-641321, AKE).
OF conceived of the study, participated in its design and coordination, performed the measurement and parts of the statistical analysis, interpreted the data and drafted and revised the manuscript. RS participated in its design, performed the measurement and parts of the statistical analysis, interpreted the data and drafted and revised the manuscript. DS, ND and IP conceived of the study, participated in its design and coordination, performed the measurement and revised the manuscript. BC, GT, HB, CG, AE, TB participated in the design and coordination of the study, interpreted the data and revised the manuscript. AM supervised the study, conceived of the study, participated in its design and coordination, performed the measurement interpreted the data and drafted and revised the manuscript. All authors read and approved the final manuscript.
Compliance with Ethical Standards
Conflict of interest
Odette Fründt received conference and travel funds for the MDS Congress in Berlin in 2016 by BIAL. Daniel Schöttle received honoria for speaking at symposia and attending symposia by Janssen-Cilag, Otsuka and Lundbeck. Götz Thomalla received fees as a consultant, lecture fees, or advisory board participation from Acandis, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Daichii Sankyo, GlaxoSmithKline, and Stryker. He received a research grant by Bayer. Christos Ganos received research support from the German Parkinson Society, and the German Research Foundation (Deutsche Forschungsgemeinschaft) and is currently funded by the VolkswagenStiftung (Freigeist-Fellowship). Besides the abovementioned funding by the European Union and the DFG (EU, “socSMCs” - H2020-641321, DFG; SFB 936/A3/C5), Ina Peiker, Nicole David and Andreas K. Engel do not have any other conflicts of interest. Tobias Bäumer received honaria for speaking at symposia form Merz Pharmaceuticals, Ipsen Pharma, Allergan and Child & Brain and served on the scientific advisory board for Merz Pharmaceuticals. Alexander Münchau served on the scientific advisory board of the Tourette Gesellschaft Deutschland (German Tourette syndrome association) and was speaker of the Lübeck Centre for Rare Diseases. He received research grants by Pharm Allergan, Ipsen, Merz Pharmaceuticals, Actelion and got honoraria for lectures from Pharm Allergan, Ipsen, Merz Pharmaceuticals, Actelion, GlaxoSmithKline, Desitin and Teva. He furthermore obtained support from non-profit foundations or societies Possehl-Stiftung, Lübeck; Dystonia Coalition (USA); Margot und Jürgen Wessel Stiftung (Lübeck), Tourette Syndrome Association (Germany); European Huntington Disease Network; N.E.MO. Charity supporting the research of paediatric movement disorders; Ärztekammer Schleswig-Holstein; Fortbildungsakademie der Deutschen Gesellschaft für Neurologie; Förderstiftung des Universitätsklinikums Schleswig-Holstein (UKSH). He furthermore received academic research support by the European Union as part of the FP 7 program (HEALTH.2011.2.2.1-3, PI, 2011–2015), the Deutsche Forschungsgemeinschaft (DFG, MU 1692/3-1, PI, 2010–2014/SFB 936, PI, 2011–2015 and 2015–2019/MU 1692/4-1, PI, 2015–2017) and the Bundesministerium für Bildung und Forschung (BMBF): DysTract consortium, PI, 2015–2018. He got royalties from the publication of the book Neurogenetics (Oxford University Press). Robert Schulz, Bastian Cheng and Hanna Braaß do not have any conflicts of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders Dsm-IV-Tr (Text Revision) (4th edn. ed.). Arlington: American Psychiatric Press Inc.Google Scholar
- Aziz-Zadeh, L., Maeda, F., Zaidel, E., Mazziotta, J., & Iacoboni, M. (2002). Lateralization in motor facilitation during action observation: A TMS study. Experimental Brain Research. Experimentelle Hirnforschung. Experimentation cerebrale, 144(1), 127–131. doi: 10.1007/s00221-002-1037-5.CrossRefPubMedGoogle Scholar
- Baron-Cohen, S., Richler, J., Bisarya, D., Gurunathan, N., & Wheelwright, S. (2003). The systemizing quotient: An investigation of adults with Asperger syndrome or high-functioning autism, and normal sex differences. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 358(1430), 361–374. doi: 10.1098/rstb.2002.1206.CrossRefPubMedPubMedCentralGoogle Scholar
- Ben Bashat, D. (2011). Abnormal developmental trajectories of white matter in autism—The contribution of MRI. In V. Eapen (Ed.), Autism—A Neurodevelopmental journey from genes to behaviour: Rijeka: InTech.Google Scholar
- Buck, T. R., Viskochil, J., Farley, M., Coon, H., McMahon, W. M., Morgan, J., et al. (2014). Psychiatric comorbidity and medication use in adults with autism spectrum disorder. Journal of Autism and Developmental Disorders, 44(12), 3063–3071. doi: 10.1007/s10803-014-2170-2.CrossRefPubMedPubMedCentralGoogle Scholar
- Chien, H. Y., Gau, S. S., Hsu, Y. C., Chen, Y. J., Lo, Y. C., Shih, Y. C., et al. (2015). Altered cortical thickness and tract integrity of the mirror neuron system and associated social communication in autism spectrum disorder. Autism Research, 8(6), 694–708. doi: 10.1002/aur.1484.CrossRefPubMedGoogle Scholar
- Christensen, D. L., Baio, J., Braun, K. V., Bilder, D., Charles, J., Constantino, J. N., et al. (2016). Prevalence and characteristics of autism spectrum disorder among children aged 8 years—Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2012. MMWR. Surveillance Summaries: Morbidity and Mortality Weekly Report. Surveillance Summaries/CDC, 65(3), 1–23. doi: 10.15585/mmwr.ss6503a1.CrossRefGoogle Scholar
- Hamilton, A. F., & Grafton, S. T. (2007). The motor hierarchy: From kinematics to goals and intentions. In P. Haggard;, Y. Rosetti; & M. Kawato, (Eds.), Attention and Performance xxii (pp. 1–29). Oxford: Oxford University Press.Google Scholar
- Hecht, E. E., Gutman, D. A., Preuss, T. M., Sanchez, M. M., Parr, L. A., & Rilling, J. K. (2013). Process versus product in social learning: Comparative diffusion tensor imaging of neural systems for action execution-observation matching in macaques, chimpanzees, and humans. Cerebral cortex (New York, N. Y.: 1991), 23(5), 1014–1024. doi: 10.1093/cercor/bhs097.CrossRefGoogle Scholar
- Izawa, J., Pekny, S. E., Marko, M. K., Haswell, C. C., Shadmehr, R., & Mostofsky, S. H. (2012). Motor learning relies on integrated sensory inputs in ADHD, but over-selectively on proprioception in autism spectrum conditions. Autism Research, 5(2), 124–136. doi: 10.1002/aur.1222.CrossRefPubMedPubMedCentralGoogle Scholar
- Lehrl, S. (2005). Mehrfachwach-Wortschatz-Intelligenztest MWT-B (5th edn). Balingen: Spitta.Google Scholar
- Mattis, S. (1988). Dementia rating scale: Professional manual. Odessa, FL: Psychological Assessment ResourcesGoogle Scholar
- Rizzolatti, G., Fadiga, L., Matelli, M., Bettinardi, V., Paulesu, E., Perani, D., et al. (1996). Localization of grasp representations in humans by PET: 1. Observation versus execution. Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale, 111(2), 246–252.CrossRefPubMedGoogle Scholar
- Rosler, M., Retz, W., Retz-Junginger, P., Thome, J., Supprian, T., Nissen, T., et al. (2004). [Tools for the diagnosis of attention-deficit/hyperactivity disorder in adults. Self-rating behaviour questionnaire and diagnostic checklist]. Der Nervenarzt, 75(9), 888–895. doi: 10.1007/s00115-003-1622-2.CrossRefPubMedGoogle Scholar
- Sasaki, A. T., Kochiyama, T., Sugiura, M., Tanabe, H. C., & Sadato, N. (2012). Neural networks for action representation: A functional magnetic-resonance imaging and dynamic causal modeling study. Frontiers in Human Neuroscience, 6, 236. doi: 10.3389/fnhum.2012.00236.CrossRefPubMedPubMedCentralGoogle Scholar
- Schaipp, C. (2001). Validität und diagnostische Brauchbarkeit ausgewählter indirekter und direkter Befragungsmethoden zur Diagnostik von Aggressivität, Neurotizismus bzw. psychischer Stabilität. München: Herbert Utz Verlag.Google Scholar
- Shih, P., Keehn, B., Oram, J. K., Leyden, K. M., Keown, C. L., & Muller, R. A. (2011). Functional differentiation of posterior superior temporal sulcus in autism: A functional connectivity magnetic resonance imaging study. Biological psychiatry, 70(3), 270–277. doi: 10.1016/j.biopsych.2011.03.040.CrossRefPubMedPubMedCentralGoogle Scholar
- von dem Hagen, E. A., Nummenmaa, L., Yu, R., Engell, A. D., Ewbank, M. P., & Calder, A. J. (2011). Autism spectrum traits in the typical population predict structure and function in the posterior superior temporal sulcus. Cerebral cortex (New York, N. Y.: 1991), 21(3), 493–500. doi: 10.1093/cercor/bhq062.CrossRefGoogle Scholar
- Wheelwright, S., Baron-Cohen, S., Goldenfeld, N., Delaney, J., Fine, D., Smith, R., et al. (2006). Predicting autism spectrum quotient (AQ) from the systemizing quotient-revised (SQ-R) and empathy quotient (EQ). Brain Research, 1079(1), 47–56. doi: 10.1016/j.brainres.2006.01.012.CrossRefPubMedGoogle Scholar
- Wittchen, H. U., Zaudig, M., & Fydrich, T. (1997). Strukturiertes Klinisches Interview für DSM-IV. Göttingen: Hogrefe.Google Scholar