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Language fMRI abnormalities associated with FOXP2 gene mutation

Nature Neuroscience volume 6, pages 1230–1237 (2003)Cite this article

Abstract

Half the members of the KE family suffer from a speech and language disorder caused by a mutation in the FOXP2 gene. We examined functional brain abnormalities associated with this mutation using two fMRI language experiments, one involving covert (silent) verb generation and the other overt (spoken) verb generation and word repetition. The unaffected family members showed a typical left-dominant distribution of activation involving Broca's area in the generation tasks and a more bilateral distribution in the repetition task, whereas the affected members showed a more posterior and more extensively bilateral pattern of activation in all tasks. Consistent with previously reported bilateral morphological abnormalities, the affected members showed significant underactivation relative to the unaffected members in Broca's area and its right homolog, as well as in other cortical language-related regions and in the putamen. Our findings suggest that the FOXP2 gene is critically involved in the development of the neural systems that mediate speech and language.

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Figure 1: Covert language task: group average fMRI activation in the unaffected and affected members of the KE family.
Figure 2: Covert language task: brain regions found to be underactive in the affected members using the interaction analysis.
Figure 3: Covert language task: percent signal change averaged across all generation/rest cycles and across subjects in each group, in representative regions of interest centered around local maxima obtained from the interaction analysis.
Figure 4: Imaging during overt language tasks.

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Acknowledgements

The authors thank J. Ashburner and C. Salmond for statistical advice, J. Ho and H. Ducie for assistance with collection of the MRI data, and the members of the KE family for their participation. This work was supported by the Wellcome Trust. Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from Research and Development Funding from the NHS Executive.

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Authors and Affiliations

  1. Developmental Cognitive Neuroscience Unit, Institute of Child Health, University College London, The Wolfson Centre, Mecklenburgh Square, London, WC1N 2AP, UK

    Frédérique Liégeois, Torsten Baldeweg & Faraneh Vargha-Khadem

  2. Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH, UK

    Frédérique Liégeois, Torsten Baldeweg, Alan Connelly, David G Gadian & Faraneh Vargha-Khadem

  3. Radiology and Physics Unit, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK

    Alan Connelly & David G Gadian

  4. Laboratory of Neuropsychology, Building 49, Room 1B80, National Institute of Mental Health, Bethesda, 20892, Maryland, USA

    Mortimer Mishkin

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  1. Frédérique Liégeois
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Correspondence to Frédérique Liégeois.

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Liégeois, F., Baldeweg, T., Connelly, A. et al. Language fMRI abnormalities associated with FOXP2 gene mutation. Nat Neurosci 6, 1230–1237 (2003). https://doi.org/10.1038/nn1138

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