Eye-Movement Intervention for Cognitive Impairment Across Schizophrenia Spectrum

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Поведенческое Eye-Movement Training
  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.
• Поведенческое Finger-Controlled Game Training
  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.

Первичные конечные точки

• Change in MATRICS Consensus Cognitive Battery (MCCB) Scores [Срок оценки: Baseline and 4-week post-intervention]
• Change in Fixation Stability Eye Movement Metrics [Срок оценки: Baseline and 4-week post-intervention]
• Change in Antisaccade Eye Movement Metrics [Срок оценки: Baseline and 4-week post-intervention]
• Change in Smooth Pursuit Eye Movement Metrics [Срок оценки: Baseline and 4-week post-intervention]
• Change in Free-Viewing Eye-tracking Metrics [Срок оценки: Baseline and 4-week post-intervention]

Вторичные конечные точки (2)

• Change in Psychosis-Risk Symptom Severity (SOPS) Scores [Срок оценки: Baseline and 4-week post-intervention]
• Change in Positive and Negative Syndrome Scale (PANSS) Scores [Срок оценки: Baseline and 4-week post-intervention]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• 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. PMID 41195081
• Kelly S, Guimond S, Lyall A, Stone WS, Shenton ME, Keshavan M, Seidman LJ. Neural correlates of cognitive deficits across developmental phases of schizophrenia. Neurobiol Dis. 2019 Nov;131:104353. doi: 10.1016/j.nbd.2018.12.013. Epub 2018 Dec 22. PMID 30582983
• Fett AJ, Reichenberg A, Velthorst E. Lifespan evolution of neurocognitive impairment in schizophrenia - A narrative review. Schizophr Res Cogn. 2022 Jan 20;28:100237. doi: 10.1016/j.scog.2022.100237. eCollection 2022 Jun. PMID 35242606
• Tschentscher N, Woll CFJ, Tafelmaier JC, Kriesche D, Bucher JC, Engel RR, Karch S. Neurocognitive Deficits in First-Episode and Chronic Psychotic Disorders: A Systematic Review from 2009 to 2022. Brain Sci. 2023 Feb 10;13(2):299. doi: 10.3390/brainsci13020299. PMID 36831842
• McCutcheon RA, Keefe RSE, McGuire PK. Cognitive impairment in schizophrenia: aetiology, pathophysiology, and treatment. Mol Psychiatry. 2023 May;28(5):1902-1918. doi: 10.1038/s41380-023-01949-9. Epub 2023 Jan 23. PMID 36690793
• Thakkar KN, Rolfs M. Disrupted Corollary Discharge in Schizophrenia: Evidence From the Oculomotor System. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 Sep;4(9):773-781. doi: 10.1016/j.bpsc.2019.03.009. Epub 2019 Apr 2. PMID 31105039
• Mitchell JP, Macrae CN, Gilchrist ID. Working memory and the suppression of reflexive saccades. J Cogn Neurosci. 2002 Jan 1;14(1):95-103. doi: 10.1162/089892902317205357. PMID 11798390
• Morita K, Miura K, Kasai K, Hashimoto R. Eye movement characteristics in schizophrenia: A recent update with clinical implications. Neuropsychopharmacol Rep. 2020 Mar;40(1):2-9. doi: 10.1002/npr2.12087. Epub 2019 Nov 27. PMID 31774633

Идентификаторы

NCT: NCT07702526 · ENI202606

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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