title: Altered cerebellar feedback projections in Asperger syndrome.
abstract: It has been proposed that the biological basis of autism spectrum disorder includes cerebellar 'disconnection'. However, direct in vivo evidence in support of this is lacking. Here, the microstructural integrity of cerebellar white matter in adults with Asperger syndrome was studied using diffusion tensor magnetic resonance tractography. Fifteen adults with Asperger syndrome and 16 age-IQ-gender-matched healthy controls underwent diffusion tensor magnetic resonance imaging. For each subject, tract-specific measurements of mean diffusivity and fractional anisotropy were made within the inferior, middle, superior cerebellar peduncles and short intracerebellar fibres. No group differences were observed in mean diffusivity. However, people with Asperger syndrome had significantly lower fractional anisotropy in the short intracerebellar fibres (p<0.001) and right superior cerebellar (output) peduncle (p<0.001) compared to controls; but no difference in the input tracts. Severity of social impairment, as measured by the Autistic Diagnostic Interview, was negatively correlated with diffusion anisotropy in the fibres of the left superior cerebellar peduncle. These findings suggest a vulnerability of specific cerebellar neural pathways in people with Asperger syndrome. The localised abnormalities in the main cerebellar outflow pathway may prevent the cerebral cortex from receiving those cerebellar feedback inputs necessary for a successful adaptive social behaviour.
authors.affiliation: Section of Brain Maturation, Department of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, London, SE58AF, UK. m.catani@iop.kcl.ac.uk
authors.forename: Marco
authors.initials: M
authors.lastname: Catani
authors.forename: Derek K
authors.initials: DK
authors.lastname: Jones
authors.forename: Eileen
authors.initials: E
authors.lastname: Daly
authors.forename: Nitzia
authors.initials: N
authors.lastname: Embiricos
authors.forename: Quinton
authors.initials: Q
authors.lastname: Deeley
authors.forename: Luca
authors.initials: L
authors.lastname: Pugliese
authors.forename: Sarah
authors.initials: S
authors.lastname: Curran
authors.forename: Dene
authors.initials: D
authors.lastname: Robertson
authors.forename: Declan G M
authors.initials: DG
authors.lastname: Murphy
mesh_terms: D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D020817:Asperger Syndrome / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology; D001519:Behavior / Q000502:physiology; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology; D003071:Cognition / Q000502:physiology; D038524:Diffusion Magnetic Resonance Imaging; D005246:Feedback / Q000502:physiology; D006801:Humans; D007361:Intelligence Tests; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales