Neural Mechanisms of Long-Term Durability of Social-Cognitive Improvement during Cognitive Enhancement Therapy for Early Course Schizophrenia

Background and Purpose: Cognitive rehabilitation has emerged as an effective practice for improving cognitive and functional outcomes in patients with schizophrenia. However, the long-term benefits of cognitive gains during such interventions is largely unknown. Recently, we observed evidence of the long-term (10 year) durability of social-cognitive improvements associated with Cognitive Enhancement Therapy (CET) in a sample of early course schizophrenia outpatients. This study sought to explore the underlying functional neural mechanisms that contributed to these lasting improvements in social cognition.

Methods: Outpatients in the early course of schizophrenia (N = 20) who were previously treated for 18 months in a randomized controlled trial of CET (N = 13) compared to Enriched Supportive Therapy (EST; N = 7) were followed up 10 years later to examine the long-term effects of CET on brain functions supporting social cognition. Participants were assessed using functional magnetic resonance imaging using two social-cognitive tasks, one assessing perspective-taking and another assessing emotion regulation. Statistical parametric maps were computed comparing brain activity during social-cognitive processing between participants treated with CET and EST, and linear regression models examined the association between brain function and improved social cognition.

Results: Analyses revealed significantly greater activation at 10 year follow-up in the medial prefrontal cortex during emotion regulation among participants treated with CET (x = -6, y = 52, z = 42, k = 72, p_uncorr < .001). While engaging in perspective-taking, individuals who received CET showed significantly greater brain activity at 10 year follow-up in both the left (x = -30, y = -76, z = -10, k = 34, p_uncorr < .001) and right fusiform gyri (x = 32, y = -76, z = -14, k = 63, p_uncorr < .001) compared to participants treated with EST. Increased right fusiform gyrus activity during perspective-taking was related to improved social cognition at 10 year follow-up (β = .46, p = .078).

Conclusions and Implications: While the results from this modest sample of participants must be considered preliminary, findings suggest that the long-term durability of social-cognitive improvement during CET in early course schizophrenia may rely on increases in fronto-temporal brain functions supporting perspective-taking and emotion regulation. These results underscore the plasticity of the brain in schizophrenia and its responsiveness to social work and other psychosocial interventions, as well as the significance of social-cognitive neural networks for the improvement of long-term outcomes in this population.