Cognitive Enhancement Therapy Improves Resting-State Functional Connectivity in Schizophrenia: Results from a Two-Year Randomized-Controlled Trial

Background and Purpose: Schizophrenia is a chronic and disabling condition that places profound burden on the individuals who suffer from it, their families, and society.  For many decades social work researchers have been developing psychosocial interventions that can be used in combination with pharmacotherapies to improve outcomes in schizophrenia.  Cognitive remediation represents one of the latest advances in psychosocial treatment for schizophrenia and utilizes computer- and group-based cognitive exercises to improve cognitive and functional recovery.  The observed benefits of cognitive remediation in a condition characterized by such a strong cognitive and neurobiological basis has led to increasing interest in its neuroplasticity (i.e., brain-changing) effects, yet few studies have examined the impact of psychosocial treatment on the brain in schizophrenia.  In this research, we sought to examine the effects of Cognitive Enhancement Therapy (CET) on fronto-temporal brain connectivity (communication) in a randomized-controlled trial of individuals with early course schizophrenia.

Methods: Stabilized, early course outpatients with schizophrenia or schizoaffective disorder were randomly assigned to CET (n = 25) or an active Enriched Supportive Therapy (EST) control (n = 16) and treated for two years along with standard antipsychotic treatment.  CET is an integrated approach to the remediation of social and non-social cognitive challenges in schizophrenia that uses of computer-assisted cognitive training and group-based experiential exercises focusing on the development of social cognition (e.g., perspective-taking, recognizing social and emotional cues).  Functional MRI data were collected prior to treatment and annually for up to two years.  Pseudo resting-state functional connectivity analysis employing an aCompCor approach was used to examine differential changes in fronto-temporal neural synchrony between those treated with CET compared to EST.  Individual growth curve models were used to investigate the association between brain connectivity changes and cognitive improvement over the course of treatment.

Results: Individuals receiving CET demonstrated significantly greater increases in functional connectivity between the posterior cingulate cortex and the left dorsolateral prefrontal cortex (k = 149, x = -34, y = 44, z = 28, p < .001), as well as between the posterior cingulate and the right insular cortex (k = 288, x = 38, y = -6, z = -4, p < .001).  These neural networks are involved in problem-solving and emotion regulation, and while individuals treated with EST showed continual decreases in connectivity between these networks over time, those receiving CET had greater positive connectivity during the course of treatment.  Further, increased positive connectivity with the right insula was associated with improved emotion perception (B = .16, p = .029), and increased connectivity with the left dorsolateral prefrontal cortex was associated with improved emotion regulation (B = .17, p = .064).

Conclusions and Implications: CET, a psychosocial cognitive remediation intervention, may enhance connections between frontal and temporal brain networks implicated in problem-solving and emotion regulation in service of cognitive enhancement in schizophrenia.  It is possible to positively influence the brain in schizophrenia with psychosocial treatment, adding to growing empirical support for the social work view of the reciprocal biopsychosocial nature of human behavior and disease.