Article

Neocerebellar Crus I Abnormalities Associated with a Speech and Language Disorder Due to a Mutation in FOXP2

Details

Citation

Argyropoulos GPD, Watkins KE, Belton-Pagnamenta E, Liégeois F, Saleem KS, Mishkin M & Vargha-Khadem F (2019) Neocerebellar Crus I Abnormalities Associated with a Speech and Language Disorder Due to a Mutation in FOXP2. Cerebellum, 18 (3), pp. 309-319. https://doi.org/10.1007/s12311-018-0989-3

Abstract
Bilateral volume reduction in the caudate nucleus has been established as a prominent brain abnormality associated with a FOXP2 mutation in affected members of the ‘KE family’, who present with developmental orofacial and verbal dyspraxia in conjunction with pervasive language deficits. Despite the gene’s early and prominent expression in the cerebellum and the evidence for reciprocal cerebellum-basal ganglia connectivity, very little is known about cerebellar abnormalities in affected KE members. Using cerebellum-specific voxel-based morphometry (VBM) and volumetry, we provide converging evidence from subsets of affected KE members scanned at three time points for grey matter (GM) volume reduction bilaterally in neocerebellar lobule VIIa Crus I compared with unaffected members and unrelated controls. We also show that right Crus I volume correlates with left and total caudate nucleus volumes in affected KE members, and that right and total Crus I volumes predict the performance of affected members in non-word repetition and non-verbal orofacial praxis. Crus I also shows bilateral hypo-activation in functional MRI in the affected KE members relative to controls during non-word repetition. The association of Crus I with key aspects of the behavioural phenotype of this FOXP2 point mutation is consistent with recent evidence of cerebellar involvement in complex motor sequencing. For the first time, specific cerebello-basal ganglia loops are implicated in the execution of complex oromotor sequences needed for human speech.

Keywords
FOXP2; Verbal dyspraxia; Cerebellum; Caudate nucleus; MRI; VIIa crus I

Journal
Cerebellum: Volume 18, Issue 3

StatusPublished
FundersMedical Research Council, Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Research and Development funding from the NHS Executive and National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London
Publication date30/06/2019
Publication date online20/11/2018
Date accepted by journal03/11/2018
URLhttp://hdl.handle.net/1893/31301
PublisherSpringer Science and Business Media LLC
ISSN1473-4222
eISSN1473-4230

People (1)

People

Dr Georgios Argyropoulos

Dr Georgios Argyropoulos

Lecturer in Psychology, Psychology