Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia

Research output: Contribution to journalArticlepeer-review


  • T Li
  • Q Wang
  • J Zhang
  • ET Rolls
  • W Yang
  • L Palaniyappan
  • L Zhang
  • W Cheng
  • Y Yao
  • Z Liu
  • X Gong
  • Q Luo
  • Y Tang
  • TJ Crow
  • K Xu
  • C Li
  • J Wang
  • Z Liu
  • G Lu
  • F Wang
  • J Feng


Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca's area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca's area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.


Original languageEnglish
Pages (from-to)436-448
Number of pages13
JournalSchizophrenia bulletin
Issue number2
Early online date21 Jul 2016
Publication statusPublished - 1 Mar 2017


  • whole brain functional-connectivity analysis, thalamus, resting-state fMRI, clinical staging model, Broca’s area