Neurophysiologic Biomarkers for Cognitive Rehabilitation

Optimization of Neurophysiologic Biomarkers for Rehabilitation Interventions in Veterans With Chronic Psychosis

Cognitive symptoms of schizophrenia interfere with daily life-from managing self-care, to more complex tasks like taking medications and living independently. Unfortunately, these cognitive symptoms are not corrected by 'standard of care' treatments (antipsychotic medications), although some schizophrenia patients may experience modest clinical and cognitive benefits from cognitive remediation. To enhance the clinical impact of cognitive remediation and other rehabilitative interventions for Veterans living with chronic psychosis, this study will develop novel brain-based tools to help identify those Veterans who are most likely to benefit from pro-cognitive therapies. These studies may advance predictive algorithms that improve functional outcomes and life quality in Veterans with schizophrenia.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia Spectrum Disorders
• Intervention / Treatment: Other: Neurophysiologic Biomarker Assessments

Detailed Description

This is an observational study recruiting Veterans with a diagnosis of Schizophrenia (SZ) and other Chronic Psychotic Disorders and Veterans in good general health (HS) who are enrolled in and/or receiving care at the VA San Diego Healthcare System. Eighty Veterans will undergo comprehensive neurophysiological, clinical, cognitive, and functional assessments in two "phases" (Phase 1: 30 SZ, 20 HS; Phase 2: 30 SZ).

In Phase 1 (Biomarker Optimization; Aims 1 & 2), Veterans will undergo systematic neurophysiologic testing designed to elicit spectral biomarkers linked to cortical excitation and inhibition ("E/I balance") during passive and stimulated conditions on two separate test visits (1-2 weeks apart). Experimental conditions will then be optimized for internal consistency and test-retest reliability using Generalizability Theory. The optimized biomarkers will be carried forward into Phase 2 (Biomarker Validation; Aim 3), where these neurophysiologic measures will be assessed before and after Veterans with SZ undergo 1 hour of cognitive training as a demonstration of neural system target engagement.

This proposal has 3 specific aims:

Aim 1. Identify the experimental conditions that optimize the psychometric properties (i.e., sensitivity to detect individual differences) of the spectral biomarkers linked to E/I balance.

Aim 2. Characterize the relationships of spectral biomarkers with rehabilitation-relevant outcomes.

Aim 3. Evaluate the sensitivity of the optimized E/I measures in predicting performance during an acute, 1-hour exposure to computerized cognitive training.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Juan Molina, MD; Phone Number: (202) 555-8975; Email: Juan.Molina@va.gov

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161-0002
      • Recruiting
      • VA San Diego Healthcare System, San Diego, CA
      • Contact: Juan Molina, MD; Phone Number: 202-555-8975; Email: Juan.Molina@va.gov
      • Principal Investigator: Juan Molina, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Veterans who are enrolled in and/or receiving healthcare services at the VA San Diego Healthcare System.

Description

Inclusion Criteria:

1. Have a DSM-5 diagnosis of a chronic psychotic disorder (e.g., schizophrenia, schizoaffective disorder, or delusional disorder); or b) are in good general mental and physical health (i.e., no active mental health condition).
2. Fluent in spoken and written English.
3. No impairment in hearing or vision.

Exclusion Criteria:

1. Active substance other than cannabis within the last 30 days as determined by self-report or positive urine toxicology (obtained as part of the screening process).
2. History of significant medical or neurological illness or intellectual disability.
3. Inability to comprehend or provide informed consent.
4. Specific to healthy comparison subjects: past or present diagnosis of schizophrenia, schizoaffective disorder, or other chronic psychotic disorder.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Biomarker Optimization - Patients; Veterans currently enrolled for healthcare services at the VA San Diego Healthcare System who have a diagnosis of a chronic psychotic disorder (e.g., schizophrenia or schizoaffective disorder).	Other: Neurophysiologic Biomarker Assessments; Non-invasive electroencephalography will be recorded to derive neurophysiologic biomarkers.
Biomarker Optimization - Healthy Comparison Subjects; Veterans currently enrolled for healthcare services at the VA San Diego Healthcare System who have no history of mental illness.	Other: Neurophysiologic Biomarker Assessments; Non-invasive electroencephalography will be recorded to derive neurophysiologic biomarkers.
Biomarker Validation in Chronic Psychotic Disorders; Veterans currently enrolled for healthcare services at the VA San Diego Healthcare System with a diagnosis of a chronic psychotic disorder (e.g., schizophrenia or schizoaffective disorder).	Other: Neurophysiologic Biomarker Assessments; Non-invasive electroencephalography will be recorded to derive neurophysiologic biomarkers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-week psychometric reliability of Aperiodic Spectral Biomarkers (neurophysiologic biomarker)	Estimates of aperiodic activity will be calculated from electroencephalography recordings collected at baseline (Day 1) and approximately 7 days later.	Approximately 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive training performance	Performance on a computerized cognitive training exercise (i.e., the "Sound Sweeps" exercise) assessing auditory processing speed. Scores range between 0-1000, with greater scores indicating worse performance.	Day 1/ Baseline
Cognition	Performance on MATRICS Consensus Cognitive Battery (MCCB). MCCB performance will be evaluated based on age- and gender-corrected T-scores (normative mean = 50; standard deviation = 10). Higher T-score values indicate better performance.	Day 1/ Baseline
Symptoms	Scores on the Positive and Negative Syndrome Scale (PANSS)	1 visit
Functioning	Scores on the World Health Organization Disability Assessment Schedule (WHODAS 2.0). WHODAS summary scores are converted into a metric ranging from 0 to 100 (where 0 = no disability; 100 = full disability).	Day 1/ Baseline
Functioning - Quality of Life	Scores on the World Health Organization Quality of Life Scale (WHOQOL-BREF). WHOQOL-BREF domain scores are converted into a metric ranging from 0 to 100 (where 0 = very poor quality of life; 100 = very good quality of life).	Day 1/ Baseline

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Juan Molina, MD, VA San Diego Healthcare System, San Diego, CA

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: July 6, 2023
• First Submitted That Met QC Criteria: July 6, 2023
• First Posted (Actual): July 14, 2023

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Schizophrenia; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorde
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: D4570-W; IK2RX004570 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No