title: Cognitive Enhancement Therapy Improves Resting-State Functional Connectivity in Early Course Schizophrenia.
abstract: OBJECTIVE
  Cognitive remediation is emerging as an effective psychosocial intervention for addressing untreated cognitive and functional impairments in persons with schizophrenia, and might achieve its benefits through neuroplastic changes in brain connectivity. This study seeks to examine the effects of cognitive enhancement therapy (CET) on fronto-temporal brain connectivity in a randomized controlled trial with individuals in the early course of schizophrenia.
  
  
  METHODS
  Stabilized, early course outpatients with schizophrenia or schizoaffective disorder (N= 41) were randomly assigned to CET (n= 25) or an active enriched supportive therapy (EST) control (n= 16) and treated for 2 years. Functional MRI data were collected annually, and pseudo resting-state functional connectivity analysis was used to examine differential changes in fronto-temporal connectivity between those treated with CET compared with EST.
  
  
  RESULTS
  Individuals receiving CET evidenced significantly less functional connectivity loss between the resting-state network and the left dorsolateral prefrontal cortex as well as significantly increased connectivity with the right insular cortex compared to EST (all correctedp< .01). These neural networks are involved in emotion processing and problem-solving. Increased connectivity with the right insula significantly mediated CET effects on improved emotion perception (z' = -1.96,p= .021), and increased connectivity with the left dorsolateral prefrontal cortex mediated CET-related improvements in emotion regulation (z' = -1.71,p= .052).
  
  
  CONCLUSIONS
  These findings provide preliminary evidence that CET, a psychosocial cognitive remediation intervention, may enhance connectivity between frontal and temporal brain regions implicated in problem-solving and emotion processing in service of cognitive enhancement in schizophrenia.
authors.affiliation: David E. Epperson Associate Professor of Social Work and an associate professor of psychiatry at the University of Pittsburgh.
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Eack
authors.affiliation: professor of social work with a joint appointment to the Clinical and Translational Science Institute at the University of Pittsburgh.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Newhill
authors.affiliation: Stanley Cobb Professor of Psychiatry at Harvard Medical School in Boston, MA.
authors.forename: Matcheri S
authors.initials: MS
authors.lastname: Keshavan
keywords: cognitive remediation; functional magnetic resonance imaging; schizophrenia; social cognition