Neuronal substrate of the saccadic inhibition deficit in schizophrenia investigated with 3-dimensional event-related functional magnetic resonance imaging

Arch Gen Psychiatry. 2002 Apr;59(4):313-20. doi: 10.1001/archpsyc.59.4.313.


Background: Several studies have shown that the ability to suppress automatic saccadic eye movements is impaired in patients with schizophrenia as well as in their first-degree relatives, and suggest that this impairment is a potential vulnerability marker for schizophrenia. The neurobiological mechanisms underlying normal saccade production and inhibition, revealed in primate studies, indicate that the impairment may result from a failure of the oculomotor system to effectively exert inhibitory control over brainstem structures. Functional localization of the affected brain structure(s) potentially provides a physiological measure for the investigation of vulnerability markers in schizophrenia.

Methods: The hemodynamic response to discrete visual stimuli was measured during prosaccades (saccades toward a peripheral stimulus), antisaccades (saccades toward a position opposite to a peripheral stimulus), and active fixation (holding fixation and ignoring a peripheral stimulus) in 16 patients with schizophrenia receiving atypical neuroleptics and 17 healthy control subjects using an event-related functional magnetic resonance imaging task design.

Results: Brain responses were detected in the frontal and parietal regions of the oculomotor system in all 3 tasks. Patients made more errors during inhibition tasks and exhibited a selective failure to activate the striatum during the inhibition of saccades. In other regions that were active during inhibition, specifically the supplementary and frontal eye fields, no difference was found between patients and control subjects.

Conclusions: A frontostriatal network is engaged in the suppression of automatic eye movements. The results indicate that abnormalities in this network, rather than the selective dysfunction of prefrontal brain regions, underlie the saccade inhibition deficit in schizophrenia.

MeSH terms

  • Adult
  • Brain / abnormalities*
  • Brain / blood supply
  • Brain Stem / blood supply
  • Brain Stem / physiopathology
  • Corpus Striatum / blood supply
  • Corpus Striatum / physiopathology
  • Electrooculography
  • Female
  • Fixation, Ocular / physiology
  • Frontal Lobe / blood supply
  • Frontal Lobe / physiopathology
  • Hemodynamics
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Nerve Net / physiopathology
  • Neural Inhibition / physiology*
  • Neurons / physiology*
  • Photic Stimulation
  • Prefrontal Cortex / blood supply
  • Prefrontal Cortex / physiopathology
  • Saccades / physiology*
  • Schizophrenia / diagnosis*
  • Schizophrenia / physiopathology*
  • Visual Fields / physiology