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Neocerebellar Crus I Abnormalities Associated with a Speech and Language Disorder Due to a Mutation in FOXP2
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
29 novembre 1916
29 novembre 1916 Mon cher Pierre, D'abord l'affaire de Jean [1]. J'ai pensé qu'en ces matières il valait mieux ne pas tarder et perdre du temps. J'ai fait remettre aujourd'hui une note à Pellé. Tu sais que le général est un ancien camarade de Stan. et que je suis en très bons termes avec lui. Je souhaite que son intervention serve à tranquilliser Paul et ta belle-sœur [2]. Je ne parle pas du Comité secret, tu as dû en apprendre aussi bien que moi toutes les circonstances. Si tu avais pu venir..