Neurophysiologic Biomarkers for Cognitive Rehabilitation

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.