Cognitive Control Errors in Nonhuman Primates Resembling Those in Schizophrenia Reflect Opposing Effects of NMDA Receptor Blockade on Causal Interactions Between Cells and Circuits in Prefrontal and Parietal Cortices.

Biological Psychiatry : Cognitive Neuroscience and Neuroimaging
Erich KummerfeldMatthew V Chafee

Abstract

The causal biology underlying schizophrenia is not well understood, but it is likely to involve a malfunction in how neurons adjust synaptic connections in response to patterns of activity in networks. We examined statistical dependencies between neural signals at the cell, local circuit, and distributed network levels in prefrontal and parietal cortices of monkeys performing a variant of the AX continuous performance task paradigm. We then quantified changes in the pattern of neural interactions across levels of scale following NMDA receptor (NMDAR) blockade and related these changes to a pattern of cognitive control errors closely matching the performance of patients with schizophrenia. We recorded the spiking activity of 1762 neurons along with local field potentials at multiple electrode sites in prefrontal and parietal cortices concurrently, and we generated binary time series indicating the presence or absence of spikes in single neurons or local field potential power above or below a threshold. We then applied causal discovery analysis to the time series to detect statistical dependencies between the signals (causal interactions) and compared the pattern of these interactions before and after NMDAR blockade. Global block...Continue Reading

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