Functional hierarchy underlies preferential connectivity disturbances in schizophrenia

Area of Science:

• Neuroscience
• Computational Psychiatry
• Brain Imaging

Background:

• Schizophrenia is hypothesized to involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits.
• The relationship between this E/I imbalance and observed neuroimaging findings remains unclear.

Purpose of the Study:

• To investigate how E/I ratio disturbances in neural models map onto large-scale functional connectivity.
• To empirically test model predictions using resting-state functional MRI data from schizophrenia patients.

Main Methods:

• Developed a neural model of large-scale functional connectivity with E/I perturbations.
• Analyzed resting-state functional MRI data from 161 schizophrenia patients and 164 healthy controls.
• Integrated hierarchical differences in neuronal dynamics into the model to explain observed patterns.

Main Results:

• The neural model predicted increased functional connectivity with elevated E/I ratios.
• Schizophrenia patients showed significantly elevated functional connectivity, correlating with symptom severity.
• This hyperconnectivity was most pronounced in association cortices, like the fronto-parietal network, and absent in bipolar disorder patients.
• Model simulations indicated preferential vulnerability of association networks to E/I imbalance.

Conclusions:

• Widespread microcircuit E/I imbalance is a plausible mechanism for the inhomogeneous dysconnectivity observed in schizophrenia.
• Altered E/I ratios provide a unifying explanation for aberrant functional connectivity patterns in schizophrenia.
• The findings highlight the role of cortical microcircuit dysfunction in the pathophysiology of schizophrenia.