Differential roles of mediodorsal nucleus of the thalamus and prefrontal cortex in decision-making and state representation in a cognitive control task measuring deficits in schizophrenia

Adele L. DeNicola, Min Yoon Park, David A. Crowe, Angus W. MacDonald, Matthew V. Chafee

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


The mediodorsal nucleus of the thalamus (MD) is reciprocally connected with the prefrontal cortex (PFC), and although the MD has been implicated in a range of PFC-dependent cognitive functions (Watanabe and Funahashi, 2012; Mitchell and Chakraborty, 2013; Parnaudeau et al., 2018), little is known about how MD neurons in the primate participate specifically in cognitive control, a capability that reflects the ability to use contextual information (such as a rule) to modify responses to environmental stimuli. To learn how the MD-PFC thalamocortical network is engaged to mediate forms of cognitive control that are selectively disrupted in schizophrenia, we trained male monkeys to perform a variant of the AX continuous performance task, which reliably measures cognitive control deficits in patients (Henderson et al., 2012) and used linear multielectrode arrays to record neural activity in the MD and PFC simultaneously. We found that the two structures made clearly different contributions to distributed processing for cognitive control: MD neurons were specialized for decision-making and response selection, whereas prefrontal neurons were specialized to preferentially encode the environmental state on which the decision was based. In addition, we observed that functional coupling between MD and PFC was strongest when the decision as to which of the two responses in the task to execute was being made. These findings delineate unique contributions of MD and PFC to distributed processing for cognitive control and characterized neural dynamics in this network associated with normative cognitive control performance. SIGNIFICANCE STATEMENT Cognitive control is fundamental to healthy human executive functioning (Miller and Cohen, 2001) and deficits in patients with schizophrenia relate to decreased functional activation of the MD thalamus and the prefrontal cortex (Minzenberg et al., 2009), which are reciprocally linked (Goldman-Rakic and Porrino, 1985; Xiao et al., 2009). We carry out simultaneous neural recordings in the MD and PFC while monkeys perform a cognitive control task translated from patients with schizophrenia to relate thalamocortical dynamics to cognitive control performance. Our data suggest that state representation and decision-making computations for cognitive control are preferentially performed by PFC and MD, respectively. This suggests experiments to parse decision-making and state representation deficits in patients while providing novel computational targets for future therapies.

Original languageEnglish (US)
Pages (from-to)1650-1667
Number of pages18
JournalJournal of Neuroscience
Issue number8
StatePublished - Feb 19 2020

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (R01MH107491, F31MH109238, and T32GM847121), Minnesota’s Discovery, Research, and Innovation Economy Neuromodulation Fellowship (Mn-DRIVE), and the American Brain Sciences Chair. This material is the result of work supported with resources and the use of facilities at the Veteran’s Affairs Medical Center in Minneapolis, MN. We thank David Redish and Sophia Vinogradov for their important insights regarding the relation of this work to state representation and cognitive

Publisher Copyright:
Copyright © 2020 the authors


  • Cognitive control
  • MD thalamus
  • Neurophysiology
  • Prefrontal
  • Primate
  • Schizophrenia
  • Neurons/physiology
  • Male
  • Schizophrenia/physiopathology
  • Electrodes, Implanted
  • Macaca mulatta
  • Animals
  • Prefrontal Cortex/physiopathology
  • Mediodorsal Thalamic Nucleus/physiopathology
  • Decision Making/physiology
  • Neural Pathways/physiology
  • Cognition/physiology

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural


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