Prefrontal brain network connectivity indicates degree of both schizophrenia risk and cognitive dysfunction

Paul G. Unschuld, Alison S. Buchholz, Mark Varvaris, Peter C M Van Zijl, Christopher A. Ross, James J. Pekar, Christoph Hock, John A. Sweeney, Carol A. Tamminga, Matcheri S. Keshavan, Godfrey D. Pearlson, Gunvant K. Thaker, David J. Schretlen

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Objective: Cognitive dysfunction is a core feature of schizophrenia, and persons at risk for schizophrenia may show subtle deficits in attention and working memory. In this study, we investigated the relationship between integrity of functional brain networks and performance in attention and working memory tasks as well as schizophrenia risk.Methods: A total of 235 adults representing 3 levels of risk (102 outpatients with schizophrenia, 70 unaffected first-degree relatives of persons with schizophrenia, and 63 unrelated healthy controls [HCs]) completed resting-state functional magnetic resonance imaging and a battery of attention and working memory tasks (Brief Test of Attention, Hopkins Verbal Learning Test, and Brief Visuospatial Memory Test) on the same day. Functional networks were defined based on coupling with seeds in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and primary visual cortex. Networks were then dissected into regional clusters of connectivity that were used to generate individual interaction matrices representing functional connectivity within each network.Results: Both patients with schizophrenia and their first-degree relatives showed cognitive dysfunction compared with HCs. First canonicals indicated an inverse relationship between cognitive performance and connectivity within the DLPFC and MPFC networks. Multivariate analysis of variance revealed multivariate main effects of higher schizophrenia risk status on increased connectivity within the DLPFC and MPFC networks.Conclusions:These data suggest that excessive connectivity within brain networks coupled to the DLPFC and MPFC, respectively, accompany cognitive deficits in persons at risk for schizophrenia. This might reflect compensatory reactions in neural systems required for cognitive processing of attention and working memory tasks to brain changes associated with schizophrenia.

Original languageEnglish (US)
Pages (from-to)653-664
Number of pages12
JournalSchizophrenia bulletin
Issue number3
StatePublished - May 2014


  • attention
  • default-mode network
  • fMRI
  • resting state
  • working memory

ASJC Scopus subject areas

  • Psychiatry and Mental health


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