Individuals with autism demonstrate atypical gaze, deficit in facial perception, altered movement perception, impairments in smooth pursuit (Rosenhall et al 1988; Scharre and Creedon, 1992; Takarae et al 2004). Substantial number of Purkinje cells in the flocculus receives converging visual inputs from functionally distinct portions of the retina and subserve the neural mechanisms for oculomotor controls during slow eye movements. The flocculus provides the oculomotor system with eye position information during fixation and with velocity information during smooth pursuit and participates in the control of the oculomotor functions (Noda and Suzuki 1979, Zee et al 1981). Oculomotor neural integrator circuit requires interaction with oculomotor neurons of the inferior olive nuclei (Ito, 1984). Presence of olivary dysplasia in three of the five autistic subjects and ectopic neurons related to the olivary complex in two cases (Bailey et al 1998) indicate that oculomotor circuitry is prone to developmental defects.
Objectives:
The aim of this study is to detect and characterize defects of the olivo-floccular circuit that may contribute to altered oculomotor function.
Methods:
Brains of 13 autistic and 14 control subjects were examined. An expanded neuropathological protocol, based on examination of one CV stained section per mm, was applied to detect type, topography and severity of qualitative changes. To detect quantitative changes, the volume of neurons and their nuclei were estimated by application of Nucleator (Mircobrightfield, VT).
Results:
The study of serial sections from one brain hemisphere including the cerebellum of 13 autistic subjects revealed multiregional dysregulation of brain development in 12 (92%) subjects. The presence of cerebellar flocculonodular dysplasia in six of 13 autistic subjects (46%), focal dysplasia in the vermis of one subject, heterotopia in one case and focal hypoplasia in one subject, reflect a high susceptibility of autistic subjects cerebellum (61% of subjects affected by one or more developmental change) and especially of the flocculus for developmental defects. The study revealed smaller by 19% volume of neurons in the inferior olive and reduced by 32% volume of Purkinje cells in children from 4 to 8 years of age.
Conclusions:
High prevalence of flocculonodular dysplasia and delayed neuronal growth of Purkinje cells and neurons in the inferior olive in children 4 to 8 years of age are the evidence of qualitative and quantitative changes in cerebellar and brainstem circuitry that may contribute to disturbed function of the oculomotor system in autism.
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