A Stereological Investigation of Regional Cerebellar Purkinje Cell Densities in Autism: Clues about Direct Gaze and Executive Function Impairments

Thursday, May 17, 2012
Sheraton Hall (Sheraton Centre Toronto)
9:00 AM
J. Skefos1, T. Yuce2, K. Enzer2, E. Levy2, K. Weed2 and M. Bauman1, (1)Anatomy & Neurobiology, Boston University School of Medicine, Boston, MA, (2)Boston University, Boston, MA
Background: Neuropathological studies within the cerebellum have implicated a decrease in Purkinje cell (PC) density in autism. However, to date, no unbiased quantitative analyses have been performed.

Objectives: Our aim was to quantify Purkinje cells in anatomically- and functionally-defined cerebellar regions, and to compare this data to ADI-R behavioral measures from each case.

Methods: We utilized systematic, random sampling technique to assess PC densities in the postmortem cerebellum obtained from eight subjects diagnosed with autism in comparison to age- and sex-matched controls. Five cerebellar regions of functional relevance to autism symptomatology were investigated.  Series of histological slides collected from the entire cerebellum of each case were provided by the Autism Tissue Program as a component of the Brain Atlas Project.

Results: PC densities within Crus I and II were consistantly significantly lower in autism cases.  Furthermore, the PC density of the Flocculonodular lobe was significantly lower in individuals with autism that demonstrated poor eye contact as assessed by the ADI-R, and the density of PC’s correlated significantly with this measure.

Conclusions: The PC’s of Crus I and II have been shown to reciprocally interact with networks in multimodal association cortices as well as frontal cortex underlying executive function, and the Flocculonodular lobe is known to modulate eye movement as well as limbic function.  These findings support the hypothesis that cerebellar developmental pathology contributes, at least in part, to the clinical autism phenotype.

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