fMRI of Eye Movement Phenotype in Schizophrenia

Summary

Principal Investigator: L Elliot Hong
Affiliation: University of Maryland
Country: USA
Abstract: The etiopathophysiology of schizophrenia is incompletely understood. Evidence supports an association between genetic liability for schizophrenia and smooth pursuit eye movement (SPEM) abnormalities, and it has been suggested that SPEM can serve as a phenotype in molecular genetic studies. However, the neural basis of reported abnormalities in SPEM is not well understood, and even less is known about how genetic effects are translated into aberrant neural circuit controlling SPEM. Knowledge of the biological mechanisms underlying SPEM abnormalities and their relationship to the schizophrenia phenotype may provide critical insights into the etiology of this disease. The goal of the proposed research is to combine functional magnetic resonance imaging (fMRI) and SPEM measures to study 1) the underlying neural mechanism of schizophrenia-related SPEM impairments; and 2) the degree to which pursuit-related imaging changes aggregate in families. We have behaviorally modeled the relative contributions of retinal motion and extraretinal motion signals to smooth pursuit maintenance in healthy subjects and in relatives of schizophrenia patients. The results indicate that performance in healthy subjects depends primarily on the predictive, or extraretinal motion input, while relatives of schizophrenia patients show deficits in this component of the pursuit response. This deficit may lead to an increased reliance on the immediate, retinal motion sensory input to maintain smooth pursuit. We hypothesize that this pattern of behavioral abnormality has a neurophysiological basis that will be detectable in fMRI imaging signal as reduced activation in the extraretinal motion processing pathway accompanied by a compensatory increase in activation in regions responsible for retinal motion processing. We further hypothesize that this pattern of neural activity will be present in the clinically unaffected siblings of affected probands, supporting a genetic influence on the neural circuit controlling predictive smooth pursuit deficit in schizophrenia.
Funding Period: 2005-02-01 - 2010-01-31
more information: NIH RePORT

Top Publications

  1. pmc Accelerated white matter aging in schizophrenia: role of white matter blood perfusion
    Susan N Wright
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
    Neurobiol Aging 35:2411-8. 2014
  2. pmc Smoking and schizophrenia independently and additively reduce white matter integrity between striatum and frontal cortex
    Xiaochu Zhang
    Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21228, USA
    Biol Psychiatry 68:674-7. 2010
  3. pmc A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA
    Proc Natl Acad Sci U S A 107:13509-14. 2010
  4. pmc Nicotine enhances but does not normalize visual sustained attention and the associated brain network in schizophrenia
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
    Schizophr Bull 37:416-25. 2011
  5. pmc Reversible inhibitors of monoamine oxidase-A (RIMAs): robust, reversible inhibition of human brain MAO-A by CX157
    Joanna S Fowler
    Medical Department, Brookhaven National Laboratory, Upton, NY, USA
    Neuropsychopharmacology 35:623-31. 2010
  6. pmc Gamma and delta neural oscillations and association with clinical symptoms under subanesthetic ketamine
    L Elliot Hong
    Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA
    Neuropsychopharmacology 35:632-40. 2010
  7. pmc Association of nicotine addiction and nicotine's actions with separate cingulate cortex functional circuits
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD 21228, USA
    Arch Gen Psychiatry 66:431-41. 2009
  8. pmc Is motion perception deficit in schizophrenia a consequence of eye-tracking abnormality?
    L Elliot Hong
    Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
    Biol Psychiatry 65:1079-85. 2009
  9. pmc Sensory gating endophenotype based on its neural oscillatory pattern and heritability estimate
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA
    Arch Gen Psychiatry 65:1008-16. 2008
  10. pmc Dopamine transporter polymorphism modulates oculomotor function and DAT1 mRNA expression in schizophrenia
    Ikwunga Wonodi
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, 21228, USA
    Am J Med Genet B Neuropsychiatr Genet 150:282-9. 2009

Scientific Experts

  • L Elliot Hong
  • Ikwunga Wonodi
  • Susan N Wright
  • Xiaochu Zhang
  • Joanna S Fowler
  • Florian Muellerklein
  • Michael G White
  • Joshua Chiappelli
  • S Andrea Wijtenburg
  • Peter Kochunov
  • Laura M Rowland
  • Robert P McMahon
  • David Alexoff
  • Elliot A Stein
  • Barbara Hubbard
  • Pauline Carter
  • Elena Shumay
  • Barry Brand
  • Lisa Muench
  • Colleen Shea
  • Amy K Poshusta
  • Daniel Burch
  • Karen Apelskog-Torres
  • Frank Telang
  • Jean Logan
  • Albert J Azzaro
  • Donald Warner
  • Robert M Fielding
  • Wei Zhu
  • Payton King
  • Mahnaz Asgharnejad
  • Michael Schueller
  • Gene Jack Wang
  • Youwen Xu
  • Millard Jayne
  • Scott Carter
  • James Free

Detail Information

Publications15

  1. pmc Accelerated white matter aging in schizophrenia: role of white matter blood perfusion
    Susan N Wright
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
    Neurobiol Aging 35:2411-8. 2014
    ..The results suggest that factors other than reduced perfusion account for the accelerated age-related decline in white matter integrity in schizophrenia...
  2. pmc Smoking and schizophrenia independently and additively reduce white matter integrity between striatum and frontal cortex
    Xiaochu Zhang
    Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21228, USA
    Biol Psychiatry 68:674-7. 2010
    ..We sought to determine whether smoking and schizophrenia are associated with similar white matter abnormalities that could be biomarkers for the high risk of smoking in schizophrenia...
  3. pmc A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA
    Proc Natl Acad Sci U S A 107:13509-14. 2010
    ..Identifying where and how brain circuits link genes to smoking provides practical neural circuitry targets for new treatment development...
  4. pmc Nicotine enhances but does not normalize visual sustained attention and the associated brain network in schizophrenia
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
    Schizophr Bull 37:416-25. 2011
    ..These findings provide guidance for developing new treatment strategies for the sustained attention deficit in schizophrenia...
  5. pmc Reversible inhibitors of monoamine oxidase-A (RIMAs): robust, reversible inhibition of human brain MAO-A by CX157
    Joanna S Fowler
    Medical Department, Brookhaven National Laboratory, Upton, NY, USA
    Neuropsychopharmacology 35:623-31. 2010
    ..These data were used to establish the dosing regimen for a current clinical efficacy trial with CX157...
  6. pmc Gamma and delta neural oscillations and association with clinical symptoms under subanesthetic ketamine
    L Elliot Hong
    Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD 21228, USA
    Neuropsychopharmacology 35:632-40. 2010
    ..These electrical oscillatory indexes of subanesthetic ketamine can be potentially used to cross-examine glutamatergic pharmacological effects in translational animal and human studies...
  7. pmc Association of nicotine addiction and nicotine's actions with separate cingulate cortex functional circuits
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD 21228, USA
    Arch Gen Psychiatry 66:431-41. 2009
    ..Imaging studies showed that nicotine challenges almost always involve the cingulate cortex, suggesting that this locus may be a key region associated with nicotine addiction and its treatment...
  8. pmc Is motion perception deficit in schizophrenia a consequence of eye-tracking abnormality?
    L Elliot Hong
    Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228, USA
    Biol Psychiatry 65:1079-85. 2009
    ..However, eye movement closely interacts with motion perception. The known eye-tracking difficulties in schizophrenia patients may interact with their motion perception...
  9. pmc Sensory gating endophenotype based on its neural oscillatory pattern and heritability estimate
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA
    Arch Gen Psychiatry 65:1008-16. 2008
    ..Frequency-specific sensory gating may be less complex than the P50 response, and therefore closer to the direct genetic effects, and thus a more valid endophenotype...
  10. pmc Dopamine transporter polymorphism modulates oculomotor function and DAT1 mRNA expression in schizophrenia
    Ikwunga Wonodi
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, 21228, USA
    Am J Med Genet B Neuropsychiatr Genet 150:282-9. 2009
    ..05), but higher expression in schizophrenia donors. Findings suggest regulatory effects of another gene(s) or etiological factor in schizophrenia, which modulate DAT1 gene function...
  11. ncbi Beta (~16 Hz) frequency neural oscillations mediate auditory sensory gating in humans
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228, USA
    Psychophysiology 45:197-204. 2008
    ..The results suggested that beta oscillation indexed a neural process associated with the strength of sensory gating...
  12. pmc Refining the predictive pursuit endophenotype in schizophrenia
    L Elliot Hong
    Maryland Psychiatric Research Center, Lions Vision Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21228, USA
    Biol Psychiatry 63:458-64. 2008
    ..Previous work has shown a reduced predictive pursuit response to a briefly masked (i.e., invisible) moving object in schizophrenia. However, the overt awareness of target removal can confound the measurement...
  13. ncbi Independent domains of inhibitory gating in schizophrenia and the effect of stimulus interval
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, P O Box 21247, Baltimore, MD 21228, USA
    Am J Psychiatry 164:61-5. 2007
    ..The authors hypothesized that the relationship of the two measures may vary as a function of interstimulus intervals of stimulus presentations...
  14. ncbi Familial aggregation of eye-tracking endophenotypes in families of schizophrenic patients
    L Elliot Hong
    Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, USA
    Arch Gen Psychiatry 63:259-64. 2006
    ..Recent studies have suggested that deficit in predictive pursuit, a specific component of the SPEMs, marks schizophrenia susceptibility...
  15. ncbi Dihydropyrimidinase-related protein 2 (DRP-2) gene and association to deficit and nondeficit schizophrenia
    L Elliot Hong
    Department of Psychiatry, Maryland Psychiatric Research Center, School of Medicine, University of Maryland, Baltimore, 21228, USA
    Am J Med Genet B Neuropsychiatr Genet 136:8-11. 2005
    ..2%, P =0.050) forms of schizophrenia compared to controls (allele frequency 25.0%). We conclude that the DRP-2 *2236 C allele may mark another polymorphism in DRP-2, or in a nearby gene, that may influence susceptibility to schizophrenia...