Language fMRI abnormalities associated with FOXP2 gene mutation

Nat Neurosci. 2003 Nov;6(11):1230-7. doi: 10.1038/nn1138. Epub 2003 Oct 12.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Mapping
  • Case-Control Studies
  • Female
  • Forkhead Transcription Factors
  • Functional Laterality
  • Humans
  • Image Processing, Computer-Assisted
  • Language Disorders / genetics*
  • Language Disorders / physiopathology
  • Language Tests
  • Language*
  • Magnetic Resonance Imaging
  • Male
  • Mutation*
  • Speech
  • Time Factors
  • Transcription Factors / genetics*
  • Verbal Behavior


  • FOXP2 protein, human
  • Forkhead Transcription Factors
  • Transcription Factors