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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:
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eye-Movement Intervention Group | Experimental | Participants in this group will receive a gamified eye-movement intervention targeting fixation control, smooth pursuit, and saccadic eye movements. The training is delivered through interactive game-based tasks including fixation-based jumping, directional gaze control, and gaze-guided visual tracking. Participants will complete 3-4 sessions per week, with each session lasting approximately 30 minutes, for a total intervention period of 4 weeks. The intervention aims to improve visuospatial attention and cognitive performance. |
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| Active Control Group (Finger-Controlled Game Training) | Active Comparator | Participants in this group will receive a finger-controlled gamified training program matched in duration, frequency, visual stimulation, and task structure to the experimental intervention. The training does not involve eye-movement control and serves as an active control condition to account for non-specific effects such as task engagement, visual exposure, and expectancy. Participants will complete 3-4 sessions per week, each lasting approximately 30 minutes, over a 4-week period. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eye-Movement Training | Behavioral | A gamified eye-movement training program designed to improve fixation control, smooth pursuit, and saccadic eye movements. The intervention includes three interactive tasks: fixation-based jumping game, gaze-direction control game, and gaze-guided visual tracking game. Participants complete 3-4 sessions per week, approximately 30 minutes per session, for 4 weeks. The intervention is delivered via a computerized eye-tracking system. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in MATRICS Consensus Cognitive Battery (MCCB) Scores | Cognitive function will be assessed using the MATRICS Consensus Cognitive Battery (MCCB), a standardized neurocognitive battery widely used in schizophrenia research. The MCCB consists of nine subtests, including Trail Making Test, Symbol Coding, Hopkins Verbal Learning Test-Revised, Spatial Span, Neuropsychological Assessment Battery Mazes, Brief Visuospatial Memory Test-Revised (BVMT-R), Category Fluency Test, Continuous Performance Test-Identical Pairs, and Mayer-Salovey-Caruso Emotional Intelligence Test-Managing Emotions. The MCCB evaluates seven cognitive domains: speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Particular attention will be given to the visual learning domain assessed by BVMT-R, which measures visuospatial memory. Changes in MCCB composite T-score, domain-specific T-scores, and BVMT-R performance from baseline to week 4 will be analyzed. | Baseline and 4-week post-intervention |
| Change in Fixation Stability Eye Movement Metrics | Fixation stability tasks will be used to assess participants' ability to maintain stable visual fixation under simple and distracted conditions. Participants will be instructed to keep their gaze on a black dot (0.5° in size) presented at the center of the screen while ignoring peripheral distractor stimuli ("*" mark, 0.5° in size). During the first 5 seconds of each trial, only the central target will be presented (simple fixation condition). During the subsequent 5-10 seconds, distractor stimuli will appear randomly around the target (distracted fixation condition), with varying locations (left/right) and eccentricities (near/far). A total of 10 trials will be conducted. Eye movement data will be recorded throughout the task. Outcome measures will include fixation duration and saccade count, reflecting fixation stability and the ability to suppress involuntary eye movements. | Baseline and 4-week post-intervention |
| Change in Antisaccade Eye Movement Metrics | Antisaccade tasks will be used to assess oculomotor inhibitory control and executive regulation. Participants will first fixate on a central cross presented on a white screen. A peripheral target will then appear at different eccentricities, and participants will be instructed to suppress the reflexive saccade toward the target and generate a voluntary saccade toward the mirror position opposite to the target location. The task will include 30 antisaccade trials, with equal numbers of near- and far-target conditions. Outcome measures will include saccade latency, error rate, and saccade velocity, reflecting response initiation, inhibitory control, and oculomotor regulation. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Psychosis-Risk Symptom Severity (SOPS) Scores | Psychosis-risk symptom severity will be assessed using the Structured Interview for Psychosis-Risk Syndromes (SIPS), with symptom severity quantified using the Scale of Psychosis-Risk Symptoms (SOPS) in clinical high-risk participants. The SOPS consists of 19 items across four domains: positive symptoms, negative symptoms, disorganized symptoms, and general symptoms. Each item is rated on a 7-point scale (0-6), with higher scores indicating greater symptom severity. The total SOPS score ranges from 0 to 114. Changes in total and domain-specific SOPS scores from baseline to week 4 will be evaluated. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tianhong Zhang, MD | Contact | 86-21-3477 3065 | zhang_tianhong@126.com |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41195081 | Background | Maldonado-Diaz M, Jara-Vargas G, Gonzalez-Seguel F. Visual attention during non-immersive virtual reality balance training in older adults with mild to moderate cognitive impairment: an eye-tracking study. Front Aging Neurosci. 2025 Oct 21;17:1671477. doi: 10.3389/fnagi.2025.1671477. eCollection 2025. | |
| 30582983 | Background |
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De-identified individual participant data (IPD) will not be publicly shared due to the sensitive nature of psychiatric clinical data, including participants with schizophrenia-spectrum disorders and individuals at clinical high risk for psychosis. The dataset contains detailed clinical, cognitive, and eye-tracking information that may increase the risk of re-identification. To protect participant confidentiality and comply with institutional ethics regulations, only aggregated results will be reported in publications.
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
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Participants will be stratified by illness stage (clinical high-risk, first-episode schizophrenia, and chronic schizophrenia) and randomly assigned in a 1:1 ratio to either an eye-movement intervention group or an active control group. The study uses a parallel-group randomized controlled design with assessor blinding.
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Participants will be stratified by illness stage (clinical high-risk, first-episode schizophrenia, and chronic schizophrenia) and randomly assigned in a 1:1 ratio to either an eye-movement intervention group or an active control group. The study uses a parallel-group randomized controlled design with assessor blinding.
|
| Finger-Controlled Game Training | Behavioral | A gamified finger-controlled training program matched in duration, frequency, visual stimulation, and task structure to the eye-movement intervention. Participants control game actions using finger inputs instead of eye movements. The intervention is designed as an active control to account for non-specific effects including engagement, visual exposure, and task expectancy. Participants complete 3-4 sessions per week, approximately 30 minutes per session, for 4 weeks. |
|
| Baseline and 4-week post-intervention |
| Change in Smooth Pursuit Eye Movement Metrics | Smooth pursuit tasks will be used to assess participants' ability to accurately track a moving visual target. Participants will be instructed to keep their heads motionless and follow a black dot presented on the screen using their eyes. The target will move according to predefined frequencies and trajectories. In the horizontal/vertical pursuit paradigm, the target will move horizontally and vertically with sinusoidal trajectories for 2.5 seconds each. In the Lissajous pursuit paradigm, the target will move simultaneously in horizontal and vertical directions using Lissajous trajectories with different frequencies and durations, including slow Lissajous pursuit (20 seconds) and fast Lissajous pursuit (10 seconds). Each trial will be repeated once. Outcome measures will include velocity gain, root mean square error (RMSE), and catch-up saccade count, reflecting pursuit accuracy, tracking precision, and compensatory eye movement responses. | Baseline and 4-week post-intervention |
| Change in Free-Viewing Eye-tracking Metrics | Free-viewing tasks will be used to assess visual exploration patterns and attentional allocation. Participants will be instructed to freely view 35 static images, including natural landscapes, social scenes, objects, and abstract patterns. Each image will be presented for 10 seconds, with participants maintaining fixation on a central cross between image presentations. Eye movement parameters will be extracted during image viewing. Outcome measures will include fixation count, fixation duration, scan path length, and mean pupil diameter, reflecting visual exploration strategies and attentional allocation. | Baseline and 4-week post-intervention |
| Baseline and 4-week post-intervention |
| Change in Positive and Negative Syndrome Scale (PANSS) Scores | Schizophrenia symptom severity will be assessed using the Positive and Negative Syndrome Scale (PANSS) in first-episode and chronic schizophrenia participants. The PANSS consists of 30 items grouped into three subscales: positive symptoms, negative symptoms, and general psychopathology. Each item is rated on a 7-point scale (1-7), with higher scores indicating greater symptom severity. The total PANSS score ranges from 30 to 210. Changes in total and subscale PANSS scores from baseline to week 4 will be evaluated. | Baseline and 4-week post-intervention |
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