Abstract
The bench-to-bedside development of pro-cognitive therapeutics for psychiatric disorders has been mired by translational failures. This is, in part, due to the absence of pharmacologically sensitive cognitive biomarkers common to humans and rodents. Here, we describe a cross-species translational marker of reward processing that is sensitive to the aminergic agonist, d-amphetamine. Motivated by human electroencephalographic (EEG) findings, we recently reported that frontal midline delta-band power is an electrophysiological biomarker of reward surprise in humans and in mice. In the current series of experiments, we determined the impact of parametric doses of d-amphetamine on this reward-related EEG response from humans (n = 23) and mice (n = 28) performing a probabilistic learning task. In humans, d-amphetamine (placebo, 10 mg, 20 mg) boosted the Reward Positivity event-related potential (ERP) component as well as the spectral delta-band representations of this signal. In mice, d-amphetamine (placebo, 0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg) boosted both reward and punishment ERP features, yet there was no modulation of spectral activities. In sum, the present results confirm the role of dopamine in the generation of the Reward Positivity in humans, and pave the way toward a pharmacologically valid biomarker of reward sensitivity across species.
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Data availability
All data and Matlab code to re-create these analyses are available at OpenNeuro.org, accession #ds003987.
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The project was funded by NIMH UH3 MH109168.
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JFC: Conceptualization, Methodology, Software, Formal analysis, Writing—Original Draft, Funding acquisition.
SLO: Investigation.
JAT: Investigation, Data curation, Supervision, Project Administration.
JEK: Investigation, Data curation, Supervision, Project Administration.
BZR: Investigation, Data curation, Supervision, Project Administration.
JAN: Investigation, Data curation, Supervision, Project Administration.
JS: Investigation, Data curation, Supervision, Project Administration.
DG: Investigation.
SGB: Conceptualization, Methodology, Investigation, Data curation, Supervision, Project Administration, Writing—Review & Editing, Funding acquisition.
GAL: Conceptualization, Methodology, Resources, Writing—Review & Editing, Funding acquisition.
NRS: Conceptualization, Methodology, Writing—Review & Editing, Investigation, Data curation, Supervision, Project Administration, Funding acquisition.
JWY: Conceptualization, Methodology, Writing—Review & Editing, Funding acquisition.
JLB: Conceptualization, Methodology, Resources, Writing—Review & Editing, Funding acquisition.
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JWY has received pharmaceutical funding from Sunovion Pharmaceuticals unrelated to the current work. All other authors report no biomedical financial interests of potential conflicts of interest.
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Cavanagh, J.F., Olguin, S.L., Talledo, J.A. et al. Amphetamine alters an EEG marker of reward processing in humans and mice. Psychopharmacology 239, 923–933 (2022). https://doi.org/10.1007/s00213-022-06082-z
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DOI: https://doi.org/10.1007/s00213-022-06082-z