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
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 160
- 主要终点
- Change in MATRICS Consensus Cognitive Battery (MCCB) Scores
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 15 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Eye-Movement Intervention Group
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.
干预措施: Eye-Movement Training (Behavioral)
Active Control Group (Finger-Controlled Game Training)
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.
干预措施: Finger-Controlled Game Training (Behavioral)
结局指标
主要结局
Change in MATRICS Consensus Cognitive Battery (MCCB) Scores
时间窗: Baseline and 4-week post-intervention
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.
Change in Fixation Stability Eye Movement Metrics
时间窗: Baseline and 4-week post-intervention
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.
Change in Antisaccade Eye Movement Metrics
时间窗: Baseline and 4-week post-intervention
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.
Change in Smooth Pursuit Eye Movement Metrics
时间窗: Baseline and 4-week post-intervention
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.
Change in Free-Viewing Eye-tracking Metrics
时间窗: Baseline and 4-week post-intervention
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.
次要结局
- Change in Psychosis-Risk Symptom Severity (SOPS) Scores(Baseline and 4-week post-intervention)
- Change in Positive and Negative Syndrome Scale (PANSS) Scores(Baseline and 4-week post-intervention)