Remediation of Visual Perceptual Impairments in Schizophrenia

It is increasingly clear that people with schizophrenia have a range of visual perception
impairments, including in low-level vision (e.g., acuity, contrast sensitivity) and mid-level
vision (e.g., perceptual organization, coherent motion detection). These impairments are
significantly related to poorer performance on cognitive (e.g., visual learning and memory)
and social cognitive (e.g., facial emotion decoding) measures, and to worse functional
outcomes. To date, there is no accepted technique for visual remediation for schizophrenia,
and almost no work has been done in this area. However, visual remediation is a
well-developed subfield within cognitive rehabilitation for traumatic brain injury (TBI)
patients, and initial studies of short-term visual perceptual learning in schizophrenia
indicate that plasticity exists that could support longer-term changes. Therefore, the
overall goal of the proposed project is to test a visual remediation intervention for
schizophrenia and determine its effects on specific visual targets with well-understood
neurobiological mechanisms. The goal of the R61 is to determine the optimal intervention for
improving the targets of contrast sensitivity (CS) and perceptual organization (PO).
Extensive evidence exists for impaired CS and PO in schizophrenia. Moreover, these targets
are prototypical examples of gain control and integration, respectively, which were
identified by the NIMH-sponsored CNTRICS initiative as being the two core mechanisms involved
in visual disturbances in the disorder. The investigators will examine two computer-based
interventions. One, ULTIMEYES (UE), targets CS. The other, contour integration training
(CIT), targets PO. The investigators will also examine the effects of combined treatment
(UE&CIT). An active computer-based control treatment will be included. There will be 40
sessions, with assessments after every 10 sessions (N=20/group). The R61 Specific Aim is to
evaluate the effects of UE and CIT on CS and PO targets, respectively, to determine if
treatment effects meet a pre-specified effect-size criterion. Results of the R61 will be used
to identify the treatment (UE, CIT, or UE&CIT) and duration (i.e., dose) that most
effectively and efficiently improves the target(s). The goal of the R33 is to conduct an
initial randomized controlled trial (RCT) of the optimal treatment identified in the R61. The
R33 Specific Aims are to: 1) replicate and extend R61 results supporting visual target
engagement in an adequately powered RCT (N=50/group); and 2) determine if visual target
engagement is associated with improvements in cognition, social cognition, and functional
capacity. If the R33 hypotheses are confirmed, results will inform the design of a later RCT
to further explore mediators and moderators of treatment effects, and to move towards a
precision medicine approach, wherein we determine which individuals are most likely to
benefit from this intervention.

Inclusion Criteria:

1. SCID-5 diagnosis of schizophrenia;

2. 18-60 years old;

3. speaks English;

4. able to complete the MATRICS Consensus Cognitive Battery (MCCB) at the baseline
assessment (for R33);

5. a raw score of 37 or greater on the Wide Range Achievement Test, Reading subtest
(WRAT-3), to establish a minimum reading level (6th grade) and to estimate premorbid
IQ; and

6. clinically stable as indicated by no antipsychotic medication changes in the last
month or if on depot, no change in the past 2 months.

Exclusion Criteria:

1. history of intellectual disability, or developmental or neurological disorder;

2. history of brain trauma associated with loss of consciousness for > 10 minutes or
behavioral sequelae;

3. alcohol or substance use disorder within the last 6 months; and

4. history of eye disease (e.g., glaucoma, retinopathy).