Beyond the disconnectivity hypothesis of schizophrenia

Edmund T. Rolls*, Wei Cheng, Matthieu Gilson, Weikang Gong, Gustavo Deco, Chun Yi Zac Lo, Albert C. Yang, Shih Jen Tsai, Mu En Liu, Ching Po Lin, Jianfeng Feng

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


To go beyond the disconnectivity hypothesis of schizophrenia, directed (effective) connectivity was measured between 94 brain regions, to provide evidence on the source of the changes in schizophrenia and a mechanistic model. Effective connectivity (EC) was measured in 180 participants with schizophrenia and 208 controls. For the significantly different effective connectivities in schizophrenia, on average the forward (stronger) effective connectivities were smaller, whereas the backward connectivities tended to be larger. Further, higher EC in schizophrenia was found from the precuneus and posterior cingulate cortex (PCC) to areas such as the parahippocampal, hippocampal, temporal, fusiform, and occipital cortices. These are backward effective connectivities and were positively correlated with the positive symptoms of schizophrenia. Lower effective connectivities were found from temporal and other regions and were negatively correlated with the symptoms, especially the negative and general symptoms. Further, a signal variance parameter was increased for areas that included the parahippocampal gyrus and hippocampus, consistent with the hypothesis that hippocampal overactivity is involved in schizophrenia. This investigation goes beyond the disconnectivity hypothesis by drawing attention to differences in schizophrenia between backprojections and forward connections, with the backward connections from the precuneus and PCC implicated in memory stronger in schizophrenia.

Original languageEnglish
Pages (from-to)1213-1233
Number of pages21
JournalCerebral Cortex
Issue number3
StatePublished - 14 Mar 2020


  • effective connectivity
  • medial prefrontal cortex
  • orbitofrontal cortex
  • posterior cingulate cortex
  • precuneus
  • schizophrenia


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