Eye-Movement Intervention for Cognitive Impairment Across Schizophrenia Spectrum

Effects of an Eye-Movement Intervention on Cognitive Impairment in Individuals Across Illness Stages of Schizophrenia: Protocol for a Stratified Randomized, Active-Controlled, Assessor-Blinded Trial

The goal of this clinical trial is to determine whether a gamified eye-movement intervention can improve cognitive function in individuals across the schizophrenia spectrum, including clinical high-risk individuals, first-episode schizophrenia patients, and chronic schizophrenia patients. The main questions it aims to answer are:

• Does eye-movement training improve cognitive performance measured by the MATRICS Consensus Cognitive Battery (MCCB)?
• Does eye-movement training improve oculomotor functions and clinical symptoms across different illness stages?

Researchers will compare an eye-movement intervention group with an active control group receiving matched finger-controlled game training to determine whether the eye-movement intervention produces greater improvements in cognitive function and eye-movement performance.

Participants will:

• Receive either gamified eye-movement training or matched finger-controlled game training for 4 weeks.
• Complete cognitive assessments using the MCCB before and after the intervention.
• Complete standardized eye-tracking tasks, including fixation stability, smooth pursuit, antisaccade, and free-viewing tasks, to evaluate changes in oculomotor control and visual exploration patterns.
• Complete clinical symptom assessments using SOPS or PANSS according to illness stage.

This study is a stratified, randomized, active-controlled, assessor-blinded clinical trial designed to evaluate the effects of a gamified eye-movement intervention on cognitive function across the schizophrenia spectrum, including clinical high-risk individuals, first-episode schizophrenia patients, chronic schizophrenia patients, and healthy controls.

Cognitive impairment is a core feature of schizophrenia-spectrum disorders and is associated with poor functional outcomes across illness stages. Eye movements are closely linked to cognitive processes such as attention, working memory, and executive control, suggesting that eye-movement-based training may have potential as a cognitive intervention.

Participants will be stratified by illness stage and randomly assigned in a 1:1 ratio to either an eye-movement intervention group or an active control group receiving matched finger-controlled game training. The intervention targets core oculomotor functions, including fixation control, smooth pursuit, and saccadic eye movements, through structured gamified training tasks. The intervention lasts 4 weeks, with 3-4 sessions per week.

The primary outcome is change in cognitive performance assessed using the MATRICS Consensus Cognitive Battery (MCCB), including composite and domain-specific T-scores from baseline to week 4. Secondary outcomes include changes in oculomotor functions and visual exploration patterns assessed using standardized eye-tracking tasks, including fixation stability, smooth pursuit, antisaccade, and free-viewing paradigms. Clinical symptom severity will be assessed using the Scale of Psychosis-Risk Symptoms (SOPS) for clinical high-risk participants and the Positive and Negative Syndrome Scale (PANSS) for schizophrenia participants.

Statistical analyses will evaluate intervention effects on cognitive, eye-movement, and clinical outcomes, including group-by-time interactions across illness stages.

Inclusion Criteria:

• Age between 15 and 45 years.
• More than 9 years of education.
• Normal or corrected-to-normal vision without color blindness, color weakness, strabismus, or nystagmus.
• Right-handedness.
• Impaired cognitive performance defined as a T-score <40 in at least one MCCB cognitive domain at baseline.
• Capacity to complete cognitive and eye-tracking assessments.
• Clinical high-risk group: Meet psychosis-risk syndrome criteria based on SIPS/SOPS, including attenuated positive symptoms or brief intermittent psychotic symptoms.
• First-episode schizophrenia group: Meet DSM-5 criteria for schizophrenia, with first episode occurring within approximately 2 years of illness onset and minimal prior antipsychotic exposure.
• Chronic schizophrenia group: Meet DSM-5 criteria for schizophrenia, with illness duration ≥5 years and stable treatment status for the previous 6 months.
• Healthy control group: No current or past psychiatric disorders based on MINI 7.0 and no significant depressive symptoms based on the Hamilton Depression Rating Scale. Healthy controls will also meet the same general criteria regarding age, education, handedness, and vision.

Exclusion Criteria:

• IQ <70.
• Severe or unstable medical or neurological illness (e.g., stroke, epilepsy, dementia, cardiac disease, or uncontrolled hypertension).
• Substance abuse or dependence.
• Clinically significant laboratory abnormalities.
• Visual or auditory impairments affecting task performance.