Neuroimaging Studies of Neurophysiological Phenotypes in Schizophrenia
Condition: Schizophrenia; Psychosis
MeSH terms: Schizophrenia; Psychotic Disorders; Mental Disorders
Study type: Observational

Summary: 
      Background:

      - Eye tracking, the ability to focus on and follow a moving target with the eyes, is often
      difficult for people who have schizophrenia. Research has shown that first-degree relatives
      of people with schizophrenia, such as parents and siblings, also tend to have difficulty with
      smooth eye movement and eye tracking. Researchers are interested in using functional magnetic
      resonance imaging (fMRI) to study brain activity during eye tracking tests in order to better
      understand the effect that schizophrenia has on brain function.

      Objectives:

      - To study eye-tracking and eye-tracking impairments in people with and without
      schizophrenia.

      Eligibility:

      - Individuals between 18 and 62 years of age in one of three groups: (1) patients who have
      been diagnosed with schizophrenia/schizoaffective disorder, (2) first-degree relatives of
      patients in group 1, and (3) healthy volunteers with no family history of psychosis.

      Design:

        -  The study will involve two visits, one screening session and one testing session. Each
           session will take about 3 hours.

        -  Participants will be asked to avoid consuming alcohol and restrict consumption of
           caffeine before the start of the study. Participants will provide urine and breath
           samples to be tested for chemicals that may interfere with the study.

        -  Participants will visit the clinical center the morning of the day before the scanning
           session to provide blood and urine samples as required. Participants will return and be
           admitted for an overnight stay later that afternoon or evening.

        -  During the screening session, participants will provide a medical and psychological
           history, provide blood samples, and learn the eye movement tasks they will do during the
           scanning session.

        -  During the scanning session, participants will have an fMRI scan. During the scan, they
           will perform eye movement tasks that involve following moving light targets on a screen,
           and will also perform other tasks that test the ability to think and pay attention.
    

Detailed description: 
      Objective:

      The proposed protocol aims to combine functional magnetic resonance imaging (fMRI) and SPEM
      eyetracking measures to study 1) the neural circuit controlling the psychophysical,
      cognitive, and oculomotor aspects of eyetracking; 2) the underlying neural mechanism of
      schizophrenia-related eyetracking impairments; and 3) the degree to which pursuit-related
      imaging changes aggregate in families. The human eye movement system is complex. It is likely
      that only components of the system, rather than the whole system, are involved in the
      pathology of schizophrenia.

      Study Population:

      Three groups of subjects will be tested: schizophrenic patients (approximately n=60), full
      siblings of patients (approximately n=60), and healthy controls without family history of
      psychosis (approximately n=60). To reach this goal of 60 per group we expect to enroll 225
      subjects.

      Design:

      Experiments in this protocol employ fMRI in combination with psychophysical and oculomotor
      paradigms to dissect the neural correlates of the neurophysiological components controlling
      pursuit eye movement. A high-resolution in-magnet eyetracking system will be used during
      imaging. Using this imaging technology we will be able to associate behavioral performance
      with specific brain regions.

      Outcome Measures:

      Combining fMRI and visual neuroscience techniques, this protocol will study the functional
      neuroanatomic underpinnings of smooth pursuit eye movement (SPEM) deficits in schizophrenia.
      We aim to establish a pathophysiological model of the illness based on the SPEM paradigm.
      Such a disease model may provide safe in vivo examination of the effects of pharmacological
      interventions, comorbidity, and functionality relating to schizophrenia. For example,
      patients with schizophrenia have high comorbidity of nicotine use. High incidence of
      substance abuse in schizophrenia suggests that the two conditions may share some common
      pathophysiology. Excessive nicotine use in schizophrenia is increasingly viewed as a form of
      self-medication by patients to correct underlying pathophysiological changes caused by the
      illness. We have found that nicotine can transiently improve smooth pursuit eye movement
      deficits in patients. We are currently examining the nicotinic effect on the learning
      components of smooth pursuit eye movement in schizophrenic patients using fMRI. This is an
      example on how carefully validated behavioral/imaging paradigm can be used as a
      pathophysiological model in aiding the study of complex brain illness including schizophrenia
      and substance abuse. Clearly, this research direction also requires a parallel research
      effort that aims at in-depth understanding of the foundational neural mechanism of the smooth
      pursuit eye movement itself.
    

Keywords: Psychosis; Smooth Pursuit; Motion Perception; Neurophysiology; fMRI