Contribution of olivofloccular circuitry developmental defects to atypical gaze in autism

Jerzy Wegiel, Izabela Kuchna, Krzysztof Nowicki, Humi Imaki, Jarek Wegiel, Yong Shuang Ma, Efrain C. Azmitia, Probal Banerjee, Michael Flory, Ira L. Cohen, Eric London, W. Ted Brown, Carolyn Komich Hare, Thomas Wisniewski

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)106-122
Number of pages17
JournalBrain Research
Volume1512
DOIs
StatePublished - 2013

Keywords

  • Atypical gaze
  • Autism
  • Cerebellum
  • Dysplasia
  • Flocculus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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