Reduced inhibition in depression impairs stimulus processing in human cortical 
microcircuits

Yao, Heng Kang; Guet-McCreight, Alexandre; Mazza, Frank; Moradi Chameh, Homeira; Prevot, Thomas D.; Griffiths, John D.; Tripathy, Shreejoy J.; Valiante, Taufik A.; Sibille, Etienne; Hay, Etay

doi:10.1016/j.celrep.2021.110232

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Journal Article

Reduced inhibition in depression impairs stimulus processing in human cortical microcircuits

MPS-Authors

Valiante, Taufik A.
External Organizations;
Max Planck - University of Toronto Centre for Neural Science and Technology, Max Planck Institute of Microstructure Physics, Max Planck Society;

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https://doi.org/10.1016/j.celrep.2021.110232
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Citation

Yao, H. K., Guet-McCreight, A., Mazza, F., Moradi Chameh, H., Prevot, T. D., Griffiths, J. D., et al. (2022). Reduced inhibition in depression impairs stimulus processing in human cortical microcircuits. Cell Reports, 38(2): 110232. doi:10.1016/j.celrep.2021.110232.

Cite as: https://hdl.handle.net/21.11116/0000-000D-8E84-E

Abstract

Cortical processing depends on finely tuned excitatory and inhibitory connections in neuronal microcircuits. Reduced inhibition by somatostatin-expressing interneurons is a key component of altered inhibition associated with treatment-resistant major depressive disorder (depression), which is implicated in cognitive deficits and rumination, but the link remains to be better established mechanistically in humans. Here we test the effect of reduced somatostatin interneuron-mediated inhibition on cortical processing in human neuronal microcircuits using a data-driven computational approach. We integrate human cellular, circuit, and gene expression data to generate detailed models of human cortical microcircuits in health and depression. We simulate microcircuit baseline and response activity and find a reduced signal-to-noise ratio and increased false/failed detection of stimuli due to a higher baseline activity in depression. We thus apply models of human cortical microcircuits to demonstrate mechanistically how reduced inhibition impairs cortical processing in depression, providing quantitative links between altered inhibition and cognitive deficits.