title: Positive or negative feedback of optokinetic signals: degree of the misrouted optic flow determines system dynamics of human ocular motor behavior.
abstract: OBJECTIVE
  The optokinetic system in healthy humans is a negative-feedback system that stabilizes gaze: slow-phase eye movements (i.e., the output signal) minimize retinal slip (i.e., the error signal). A positive-feedback optokinetic system may exist due to the misrouting of optic fibers. Previous studies have shown that, in a zebrafish mutant with a high degree of the misrouting, the optokinetic response (OKR) is reversed. As a result, slow-phase eye movements amplify retinal slip, forming a positive-feedback optokinetic loop. The positive-feedback optokinetic system cannot stabilize gaze, thus leading to spontaneous eye oscillations (SEOs). Because the misrouting in human patients (e.g., with a condition of albinism or achiasmia) is partial, both positive- and negative-feedback loops co-exist. How this co-existence affects human ocular motor behavior remains unclear.
  
  
  METHODS
  We presented a visual environment consisting of two stimuli in different parts of the visual field to healthy subjects. One mimicked positive-feedback optokinetic signals and the other preserved negative-feedback optokinetic signals. By changing the ratio and position of the visual field of these visual stimuli, various optic nerve misrouting patterns were simulated. Eye-movement responses to stationary and moving stimuli were measured and compared with computer simulations. The SEOs were correlated with the magnitude of the virtual positive-feedback optokinetic effect.
  
  
  RESULTS
  We found a correlation among the simulated misrouting, the corresponding OKR, and the SEOs in humans. The proportion of the simulated misrouting needed to be greater than 50% to reverse the OKR and at least greater than or equal to 70% to evoke SEOs. Once the SEOs were evoked, the magnitude positively correlated to the strength of the positive-feedback OKR.
  
  
  CONCLUSIONS
  This study provides a mechanism of how the misrouting of optic fibers in humans could lead to SEOs, offering a possible explanation for a subtype of infantile nystagmus syndrome (INS).
authors.affiliation: Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Chien-Cheng
authors.initials: CC
authors.lastname: Chen
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bockisch
authors.forename: Itsaso
authors.initials: I
authors.lastname: Olasagasti
authors.forename: Konrad P
authors.initials: KP
authors.lastname: Weber
authors.forename: Dominik
authors.initials: D
authors.lastname: Straumann
authors.forename: Melody Ying-Yu
authors.initials: MY
authors.lastname: Huang
mesh_terms: D000328:Adult; D056228:Feedback, Sensory / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D017120:Nystagmus, Optokinetic / Q000502:physiology*; D009759:Nystagmus, Pathologic / Q000503:physiopathology; D057849:Optic Flow / Q000502:physiology*; D010775:Photic Stimulation; D012016:Reference Values; D014741:Video Recording; D055815:Young Adult
keywords: infantile nystagmus syndrome (INS); misrouting of optic fibers; optokinetic response (OKR); positive and negative feedback optokinetic systems; spontaneous eye oscillations