# Optimization of Neurophysiologic Biomarkers for Rehabilitation Interventions in Veterans with Chronic Psychosis

> **NIH VA IK2** · VA SAN DIEGO HEALTHCARE SYSTEM · 2023 · —

## Abstract

In response to RX-22-017, this Career Development Award-2 (CDA-2) provides a mentored research
and training program for an early career psychiatrist, committed to advancing Veteran’s health and wellbeing
and to becoming an independent RR&D Investigator. This application develops a novel biomarker linked to
cortical function for applications in “precision rehabilitation” trials for Veterans with schizophrenia (SZ).
 Despite advances in clinical neuroscience, there are no effective treatments for the cognitive
impairment in SZ; this impairment is a primary contributor to significant disability for Veterans with SZ and
limits their function, independence, and quality of life. Modest clinical benefits can be achieved with specific
rehabilitative interventions, e.g., Targeted Cognitive Training (TCT), but such treatments are time- and
resource-intensive, and treatment responses are incomplete and variable. Predictive biomarkers could aid in
the prospective identification of patients most likely to benefit from TCT and other rehabilitative interventions,
but the lack of such biomarkers
has limited the effectiveness of these treatments.
 Recently, an index of cortical excitation and inhibition (“E/I balance”) has been proposed as a
translational biomarker for pro-cognitive interventions. Conceptually, E/I balance reflects the integrated activity
of specific cell types in the cerebral cortex. Abnormalities in E/I balance have been implicated in the
pathophysiology of the cognitive, perceptual, and social impairment associated with SZ. In Molina et al. (2020),
we reported the first in vivo evidence of abnormal E/I balance in SZ patients; these electroencephalographic
(EEG) abnormalities were transiently ‘normalized’ by a pro-cognitive modulator of cortical excitability. This
study provides evidence that E/I balance may index neural mechanisms that support cognitive rehabilitation;
conceivably, such a measure might serve as a predictive biomarker for pro-cognitive interventions. This
application takes the steps needed to develop E/I balance as a predictive tool for large-scale application in
prospective rehabilitation trials of pro-cognitive interventions in Veterans with SZ.
 To develop this potential biomarker for rehabilitation trials, this application will establish both the
reliability and internal consistency of E/I balance in a Veteran clinical cohort. Past studies assessed E/I balance
in the context of drug manipulations, using an EEG “session of convenience” with complex sensory stimuli; this
application assesses E/I without drug-challenge and under conditions of both sensory stimulation and rest. The
relationship of E/I balance to cognition and function will also be assessed. By optimizing the experimental
conditions for measuring E/I balance, this application will increase the likelihood that this biomarker will be
capable of distinguishing differences between subjects—a prerequisite for matching the “right Veteran” to the
“right intervention” i...

## Key facts

- **NIH application ID:** 10753415
- **Project number:** 1IK2RX004570-01A1
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** JUAN MOLINA
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10753415

## Citation

> US National Institutes of Health, RePORTER application 10753415, Optimization of Neurophysiologic Biomarkers for Rehabilitation Interventions in Veterans with Chronic Psychosis (1IK2RX004570-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10753415. Licensed CC0.

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