Dorsolateral Prefrontal Cortex Activity Predicts Responsiveness to Cognitive-Behavioral Therapy in Schizophrenia

Background: Given the variable response to cognitive-behavioral therapy (CBT) when added to antipsychotic medication in psychosis and the evidence for a role of pretherapy level of frontal lobe-based cognitive function in responsiveness to CBT in other disorders, this study examined whether pretherapy brain activity associated with working memory neural network predicts clinical responsiveness to CBT in schizophrenia. Methods: Fifty-two outpatients stable on medication with at least one distressing symptom of schizophrenia and willing to receive CBT in addition to their usual treatment and 20 healthy participants underwent functional magnetic resonance imaging during a parametric n-back task. Subsequently, 26 patients received CBT for psychosis (CBT+treatment-as-usual [TAU], 19 completers) for 6-8 months, and 26 continued with TAU alone (17 completers). Symptoms in both patient groups were assessed (blindly) at entry and follow-up. Results: The CBT+TAU and TAU-alone groups did not differ clinically or in performance at baseline. The CBT+TAU group showed significant improvement in relation to the TAU-alone group, which showed no change, at follow-up. Stronger dorsolateral prefrontal cortex (DLPFC) activity (within the normal range) and DLPFC-cerebellum connectivity during the highest memory load condition (2-back > 0-back) were associated with post-CBT clinical improvement. Conclusions: DLPFC activity and its connectivity with the cerebellum predict responsiveness to CBT for psychosis in schizophrenia. These effects may be mediated by PFC-cerebellum contributions to executive processing.