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White Matter Microstructure of the Human Mirror Neuron System is Related to Symptom Severity in Adults with Autism

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Abstract

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.

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Acknowledgments

We would like to thank the patients for their participation in the study.

Funding

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).

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    Authors and Affiliations

    1. Department of Neurology, University Medical Center Hamburg-Eppendorf (UKE), Martinistraße 52, 20246, Hamburg, Germany

      Odette Fründt, Robert Schulz, Bastian Cheng, Götz Thomalla, Hanna Braaß, Christos Ganos, Tobias Bäumer & Alexander Münchau

    2. Department of Psychiatry, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany

      Daniel Schöttle

    3. Department of Neurophysiology and Pathophysiology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany

      Nicole David, Ina Peiker & Andreas K. Engel

    4. Department of Pediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, University of Lübeck, Lübeck, Germany

      Tobias Bäumer & Alexander Münchau

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    Contributions

    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.

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    Correspondence to Odette Fründt.

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    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.

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    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.

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    Informed consent was obtained from all individual participants included in the study.

    Additional information

    Odette Fründt and Robert Schulz have contributed equally to this work.

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    Fründt, O., Schulz, R., Schöttle, D. et al. White Matter Microstructure of the Human Mirror Neuron System is Related to Symptom Severity in Adults with Autism. J Autism Dev Disord 48, 417–429 (2018). https://doi.org/10.1007/s10803-017-3332-9

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