Functional hierarchy underlies preferential connectivity disturbances in schizophrenia

Genevieve J. Yang, John D. Murray, Xiao Jing Wang, David C. Glahn, Godfrey D. Pearlson, Grega Repovs, John H. Krystal, Alan Anticevic

Research output: Contribution to journalArticlepeer-review


Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined restingstate functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.

Original languageEnglish (US)
Pages (from-to)E219-E228
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number2
StatePublished - Jan 12 2016


  • Computational modeling
  • Functional connectivity
  • Schizophrenia

ASJC Scopus subject areas

  • General


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