Neuroimaging predictors of cognitive benefits after virtual reality-based cognitive remediation in mood or schizophrenia spectrum disorders.

Cognitive impairment is a core feature across mood disorders (MD) and schizophrenia spectrum disorders (SSD), but effective replicated pro-cognitive treatments are lacking. Identifying neuroimaging biomarkers that predict treatment efficacy can aid development of more effective and personalized treatment strategies. Virtual reality-based cognitive remediation therapy (VR-CRT) improves cognition and increases task-related neurocircuitry activity in the dorsal prefrontal cortex (dPFC) in MD or SSD. This study investigates if pre-treatment functional and structural neuroimaging features can predict cognitive benefits after VR-CRT. Thirty-six cognitively impaired individuals with clinically stable MD or SSD underwent neuropsychological assessment and magnetic resonance imaging (MRI) at baseline and after completion of either a four-week VR-CRT intervention (n = 20) or VR control treatment (n = 16). Linear regression analyses were conducted to assess if pre-treatment dPFC neurocircuitry activity and thickness were associated with greater VR-CRT-related benefits on global cognition. Lower baseline activity in the left superior frontal gyrus during memory encoding was associated with greater VR-CRT-related improvements in global cognition at treatment completion (β = -1.40, 95% CI [-2.45; -0.35], p = 0.01) but not at three-months follow-up (p = 0.16). Cortical thickness in the dPFC was not related to treatment effects on cognition (ps≥0.28). In conclusion, lower pre-treatment dPFC neurocircuitry activity is associated with greater cognitive benefits after VR-CRT across individuals with MD or SSD. If replicated, dPFC hypoactivation may represent a transdiagnostic neural biomarker predicting enhanced cognitive gains from VR-based cognitive training.