Abnormal functional activation and connectivity in the working memory network in early-onset schizophrenia

Marinos Kyriakopoulos, Danai Dima, Jonathan P. Roiser, Richard Corrigall, Gareth J. Barker, Sophia Frangou

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Disruption within the working memory (WM) neural network is considered an integral feature of schizophrenia. The WM network, and the dorsolateral prefrontal cortex (DLPFC) in particular, undergo significant remodeling in late adolescence. Potential interactions between developmental changes in the WM network and disease-related processes for schizophrenia remain unclear. The aim of this study was to determine whether DLPFC activation and functional connectivity are impaired during WM in patients with early-onset schizophrenia (EOS; age of onset <18 years). We used functional magnetic resonance imaging and psychophysiological interaction analysis to respectively measure blood oxygenation leveldependent signal and to derive functional connectivity estimates in response to the two-back WM task from 25 youths with EOS and 20 matched healthy adolescents. Compared with healthy adolescents, patients with EOS showed reduced engagement of the DLPFC, the anterior cingulate cortex (ACC), and frontal operculum, and had reduced DLPFC connectivity within the WM network. Patients with EOS showed abnormal reduction in the coupling of the DLPFC with the ACC, the inferior parietal lobule, and the middle occipital gyrus. In contrast to healthy adolescents, patients with EOS expressed age-related decrease in the activity of the DLPFC and an increase in its connectivity with the ACC. Patients with EOS show dysfunctional engagement and reduced integration within the WM neural network. The pattern of abnormal age-related correlations in DLPFC activity and connectivity suggests that schizophrenia-related processes have an impact on brain regions that show significant late developmental changes.

Original languageEnglish
Pages (from-to)911-920.e2
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number9
StatePublished - Sep 2012
Externally publishedYes


  • PPI
  • early onset schizophrenia
  • fMRI
  • psychological interaction
  • working memory


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