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

AbstractBilateral volume reduction in the caudate nucleus has been established as a prominent brain abnormality associated with aFOXP2 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 cere bellar 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 co mpared 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 orofac ial 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 thisFOXP2 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 execu...
Source: The Cerebellum - Category: Neurology Source Type: research