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Concordant neurophysiological signatures of cognitive control in humans and rats

Abstract

Progress towards understanding neural mechanisms in humans relevant to psychiatric conditions has been hindered by a lack of translationally-relevant cognitive tasks for laboratory animals. Accordingly, there is a critical need to develop parallel neurophysiological assessments of domains of cognition, such as cognitive control, in humans and laboratory animals. To address this, we developed a touchscreen-based cognitive (Eriksen Flanker) task in rats and used its key characteristics to construct a novel human version, with similar testing parameters and endpoints across species. We obtained continuous electroencephalogram (EEG) recordings, including local field potentials in rats, and compared electrophysiological signatures locked to stimulus onset and responses across species. We also assessed whether behavioral or physiological task effects were modulated by modafinil, which enhances aspects of cognitive function in humans. In both species, the task elicited expected flanker interference effects (reduced accuracy) during high-conflict trials. Across homologous neuroanatomical loci, stimulus-locked increases in theta power during high-conflict trials as well as error-related negative potentials were observed. These endpoints were not affected by modafinil in either species. Despite some species-specific patterns, our findings demonstrate the feasibility of a rat Flanker task as well as cross-species behavioral and neurophysiological similarities, which may enable novel insights into the neural correlates of healthy and aberrant behavior and provide mechanistic insights relevant to treatment.

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Fig. 1: Flanker task design.
Fig. 2: Behavioral results.
Fig. 3: Stimulus-locked event-related potentials.
Fig. 4: Stimulus-locked wavelets.
Fig. 5: Response-locked event-related potentials.
Fig. 6: Response-locked wavelets.

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Acknowledgements

We would like to acknowledge the members of our scientific advisory board, Dr. Cindy Ehlers, Dr. Stan Floresco, Dr. Patricio O’Donnell, and Dr. Steven Siegel, for their assistance in the development and execution of these studies. We would also like to thank Dr. Jennifer Evans for her comments on the manuscript and Dr. David P. Olson for assistance with the medical components of the study. Finally, we would like to acknowledge Dr. Boyu Ren for his assistance with statistical analyses.

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MAR—design of the work. Acquisition, analysis, and interpretation of data. Drafting of manuscript. HSS—design of the work. Acquisition, analysis, and interpretation of data. Drafting of manuscript. BDK—design of the work. Interpretation of data. Revision of the manuscript. SN—design of the work. Acquisition, analysis, and interpretation of data. MB—acquisition and analysis of data. AMI-M—analysis and interpretation of data. SP—acquisition of data. EC—acquisition of data. AD-A—design of work. Interpretation of data. Revision of the manuscript. SAB—interpretation of data. Revision of the manuscript. SL—design of work. Interpretation of data. VBR—design of work. Interpretation of data. Revision of the manuscript. GV—acquisition of data, medical evaluations. Revision of the manuscript. JB—design of work. Interpretation of data. Revision of the manuscript. WAC Jr.—design of work. Interpretation of data. Revision of the manuscript. DAP—design of work. Analysis and interpretation of data. Revision of the manuscript. Secured funding.

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Correspondence to Diego A. Pizzagalli.

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Robble, M.A., Schroder, H.S., Kangas, B.D. et al. Concordant neurophysiological signatures of cognitive control in humans and rats. Neuropsychopharmacol. (2021). https://doi.org/10.1038/s41386-021-00998-4

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