title: Contribution of olivofloccular circuitry developmental defects to atypical gaze in autism.
abstract: Individuals with autism demonstrate atypical gaze, impairments in smooth pursuit, altered movement perception and deficits in facial perception. The olivofloccular neuronal circuit is a major contributor to eye movement control. This study of the cerebellum in 12 autistic and 10 control subjects revealed dysplastic changes in the flocculus of eight autistic (67%) and two control (20%) subjects. Defects of the oculomotor system, including avoidance of eye contact and poor or no eye contact, were reported in 88% of autistic subjects with postmortem-detected floccular dysplasia. Focal disorganization of the flocculus cytoarchitecture with deficit, altered morphology, and spatial disorientation of Purkinje cells (PCs); deficit and abnormalities of granule, basket, stellate and unipolar brush cells; and structural defects and abnormal orientation of Bergmann glia are indicators of profound disruption of flocculus circuitry in a dysplastic area. The average volume of PCs was 26% less in the dysplastic region than in the unaffected region of the flocculus (p<0.01) in autistic subjects. Moreover, the average volume of PCs in the entire cerebellum was 25% less in the autistic subjects than in the control subjects (p<0.001). Findings from this study and a parallel study of the inferior olive (IO) suggest that focal floccular dysplasia combined with IO neurons and PC developmental defects may contribute to oculomotor system dysfunction and atypical gaze in autistic subjects.
authors.affiliation: Department of Developmental Neurobiology, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, United States. jerzy.wegiel@opwdd.ny.gov
authors.forename: Jerzy
authors.initials: J
authors.lastname: Wegiel
authors.forename: Izabela
authors.initials: I
authors.lastname: Kuchna
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Nowicki
authors.forename: Humi
authors.initials: H
authors.lastname: Imaki
authors.forename: Jarek
authors.initials: J
authors.lastname: Wegiel
authors.forename: Shuang Yong
authors.initials: SY
authors.lastname: Ma
authors.forename: Efrain C
authors.initials: EC
authors.lastname: Azmitia
authors.forename: Probal
authors.initials: P
authors.lastname: Banerjee
authors.forename: Michael
authors.initials: M
authors.lastname: Flory
authors.forename: Ira L
authors.initials: IL
authors.lastname: Cohen
authors.forename: Eric
authors.initials: E
authors.lastname: London
authors.forename: W Ted
authors.initials: WT
authors.lastname: Brown
authors.forename: Carolyn
authors.initials: C
authors.lastname: Komich Hare
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001321:Autistic Disorder / Q000150:complications*; D002531:Cerebellum / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000150:complications* / Q000473:pathology; D003936:Diagnosis, Computer-Assisted; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D015835:Ocular Motility Disorders / Q000209:etiology*; D009847:Olivary Nucleus / Q000378:metabolism / Q000473:pathology*; D011180:Postmortem Changes; D011689:Purkinje Cells / Q000473:pathology; D011698:Pursuit, Smooth / Q000502:physiology*; D055815:Young Adult
chemical_list: D009419:Nerve Tissue Proteins
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