cerebellar connections in Autism

[Guest guest]

Cerebellar Connections in Autism: Specific Changes in Intrinsic

Circuitry and Cerebellar Outputs

Marco Catani, London, United Kingdom, Eileen Daly, Nitzia Embrikos,

K. , Quinton Deeley, G. , London, United Kingdom

OBJECTIVE: To study integrity of cerebellar connections in autism.

BACKGROUND: There are studies suggesting that the cerebellum is affected

in autistic spectrum disorder (ASD). Reduced purkinje cells density is a

consistent finding in post-mortem studies, and an intense inflammatory

process affecting cerebellar white matter has recently been documented

(Vargas et al., Ann Neurol 2005). Also, some have reported (Carper and

Courchesne, Brain 2000) a link between increased volume of frontal lobe

and decreased volume of cerebellum in ASD. Thus a

cerebello-thalamic-frontal disconnection theory has been proposed, where

reduced inhibitory purkinje cell input to deep cerebellar nuclei leads

to excessive excitatory output from the cerebellum, and consequently

frontal overgrowth. However nobody has directly examined cerebellar

connectivity in ASD. Hence we used Diffusion Tensor tractography to

explore white matter integrity of i) local intracerebellar circuitry and

ii) long cerebellar tracts. DESIGN/METHODS: Two groups of right-handed

males, IQ > 70, were recruited: 15 high functioning subjects with ASD

(age 31 9 years) and 15 healthy controls (age 35 11 years). Tractography

was used to dissect the superior, middle and inferior cerebellar

pedunculi (long connections) and short intracerebellar fibres (local

circuitry), according to a method described in Catani et al.,

(Neuroimage 2002). RESULTS: Overall fractional anisotropy (FA) was

significantly reduced in the ASD as compared to controls (0.446 vs

0.461; F 7.669; df 1; p = 0.01). Post-hoc comparisons of individual

tracts showed significant FA reduction in the right superior cerebellar

pedunculus (0.456 vs 0.482, p=0.009) and the right short intracerebellar

fibres (0.32 vs 0.36, p<0.0001) in the ASD group. CONCLUSIONS/RELEVANCE:

The study confirm significant abnormalities in cerebellar white matter

tracts of ASD. Reduced FA of the short intracerebellar fibres indicates

changes in intracerebellar circuitry, whereas differences in the

superior cerebellar pedunculus suggest selective impairment of

cerebellar-thalamic output, and perhaps a specific disconnectivity

between right cerebellum and left hemisphere.

Category - Child Neurology/Developmental Neurobiology

SubCategory - Imaging

Thursday, April 6, 2006 2:45 PM