Eye-Movement Intervention for Cognitive Impairment Across Schizophrenia Spectrum

NCT07702526 | Not Yet Recruiting

• 1 other identifier: ENI202606
• Study Type: interventional
• Target: 160
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Schizophrenia; Cognitive Impairment; Clinical High Risk for Psychosis

Keywords

Eye movement training; Cognitive remediation; BVMT-R; Visuospatial memory; Eye tracking

Outcome Measures

Primary Outcomes (5)

• 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.

  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

Secondary Outcomes (2)

• 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

Study Arms (2)

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.

Behavioral: Eye-Movement Training

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.

Behavioral: Finger-Controlled Game Training

Interventions

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.

Eye-Movement Intervention Group

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.

Active Control Group (Finger-Controlled Game Training)

Eligibility Criteria

• Age: 15 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Mental Health Center: lead

Related Publications (17)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Wolf A, Ueda K, Hirano Y. Recent updates of eye movement abnormalities in patients with schizophrenia: A scoping review. Psychiatry Clin Neurosci. 2021 Mar;75(3):82-100. doi: 10.1111/pcn.13188. Epub 2021 Jan 20.

  PMID: 33314465 BACKGROUND

• Dickinson D, Tenhula W, Morris S, Brown C, Peer J, Spencer K, Li L, Gold JM, Bellack AS. A randomized, controlled trial of computer-assisted cognitive remediation for schizophrenia. Am J Psychiatry. 2010 Feb;167(2):170-80. doi: 10.1176/appi.ajp.2009.09020264. Epub 2009 Dec 15.

  PMID: 20008941 BACKGROUND

• Wykes T, Huddy V, Cellard C, McGurk SR, Czobor P. A meta-analysis of cognitive remediation for schizophrenia: methodology and effect sizes. Am J Psychiatry. 2011 May;168(5):472-85. doi: 10.1176/appi.ajp.2010.10060855. Epub 2011 Mar 15.

  PMID: 21406461 BACKGROUND

• Fioravanti M, Bianchi V, Cinti ME. Cognitive deficits in schizophrenia: an updated metanalysis of the scientific evidence. BMC Psychiatry. 2012 Jun 20;12:64. doi: 10.1186/1471-244X-12-64.

  PMID: 22715980 BACKGROUND

• Shaikh MF, Higley C, Campanile C, Francis R, Panja E, Santacaterina S, Pratesi G, Piaggio D. Serious gaming and eye-tracking for the screening, monitoring, and diagnosis of neurodevelopmental disorders in children: a systematic literature review. Front Bioeng Biotechnol. 2026 Jan 14;13:1672718. doi: 10.3389/fbioe.2025.1672718. eCollection 2025.

  PMID: 41613152 BACKGROUND

• Anguera JA, Boccanfuso J, Rintoul JL, Al-Hashimi O, Faraji F, Janowich J, Kong E, Larraburo Y, Rolle C, Johnston E, Gazzaley A. Video game training enhances cognitive control in older adults. Nature. 2013 Sep 5;501(7465):97-101. doi: 10.1038/nature12486.

  PMID: 24005416 BACKGROUND

• Torous J, Bucci S, Bell IH, Kessing LV, Faurholt-Jepsen M, Whelan P, Carvalho AF, Keshavan M, Linardon J, Firth J. The growing field of digital psychiatry: current evidence and the future of apps, social media, chatbots, and virtual reality. World Psychiatry. 2021 Oct;20(3):318-335. doi: 10.1002/wps.20883.

  PMID: 34505369 BACKGROUND

• Wang W, You M, Ma W, Yang Y. Effect of eye-tracking-based attention training for patients with poststroke cognitive impairment: a study protocol for a prospective, single-blinded, single-centre, randomised controlled trial in China. BMJ Open. 2024 Feb 14;14(2):e079917. doi: 10.1136/bmjopen-2023-079917.

  PMID: 38355177 BACKGROUND

• Kessler L, Legaludec V, Dietemann JL, Maitrot D, Pinget M. Sphenoidal sinus mucocele after transsphenoidal surgery for acromegaly. Neurosurg Rev. 1999 Dec;22(4):222-5. doi: 10.1007/s101430050021.

  PMID: 10682932 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Central Study Contacts

Tianhong Zhang, MD

CONTACT

86-21-3477 3065; zhang_tianhong@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 14, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): July 30, 2028
• Last Updated: July 14, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share