From default-mode to action-mode: biphasic network reconfiguration with meditation in schizophrenia

IntroductionMeditation is widely used to support mental well-being, and recent randomized trials suggest benefits for persistent psychotic symptoms in schizophrenia. However, the magnitude and timing of causal treatment effects, response heterogeneity, and underlying neurobiological mechanisms over clinically meaningful timescales remain unclear. MethodsWe analyzed data from an eight-month, parallel-group randomized clinical trial (ChiCTR1800014913) of 64 male inpatients with chronic schizophrenia, randomized to daily clinician-guided meditation plus rehabilitation or rehabilitation alone. Prespecified outcomes were PANSS percentage decrease rate and RBANS increase rate. Linear mixed-effects models estimated time-specific causal average treatment effects. Cross-lagged panel models examined temporal relations between symptom and cognitive benefits; latent-class mixed models characterized treatment-response heterogeneity. Resting-state fMRI at baseline, 3, and 8 months yielded functional components, their complexity indices, and functional-connectivity predictors of clinical benefit. ResultsMeditation produced progressive symptom improvement (average treatment effects on PANSS decrease rate: 11.8% after 3 months; 20.8% after 8 months) and an early cognitive gain (7.6% after 3 months) that plateaued. Early cognitive improvement predicted, but did not mediate, later symptom relief. Response trajectories were heterogeneous; marital status and lower antipsychotic burden characterized high responders. Neuroimaging revealed a biphasic pattern: higher baseline default-mode-cerebellar complexity predicted short-term benefit, whereas greater 3-month action-mode-sensorimotor-executive complexity predicted longer-term gains; functional-connectivity models converged on these findings. ConclusionsClinician-guided meditation, added to rehabilitation, yields robust causal treatment effects on symptoms in schizophrenia. A biphasic shift from default-mode-cerebellar involvement to action-mode engagement provides phase-specific, information-based indicators to guide personalized meditation in severe mental illness.