Amphetamine alters an EEG marker of reward processing in humans and mice

Abstract

The development of pro-cognitive therapeutics for psychiatric disorders has been beset with difficulties. 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 measure of reward processing that is sensitive to the dopamine agonist, d-amphetamine. Motivated by human electroencephalographic (EEG) findings, we recently reported that frontal midline delta-band power is also an electrophysiological biomarker of reward surprise in mice. Here, we determined the impact on this reward-related EEG response from humans (n=23) and mice (n=28) performing a probabilistic learning task under parametric doses of d-amphetamine (human: placebo, 10 mg, 20 mg; mice: placebo, 0.1 mg/kg, 0.3 mg.kg, 1.0 mg/kg). In humans, d-amphetamine boosted the Reward Positivity event-related potential (ERP) component as well as the spectral delta-band representation of this signal. In mice, only the Reward Positivity ERP component was significantly boosted by d-amphetamine. In sum, the present results confirm the role of dopamine in the generation of the Reward Positivity, and support the first pharmacologically valid biomarker of reward sensitivity across species.

Hypoactivation of ventromedial frontal cortex in major depressive disorder: an MEG study of the Reward Positivity

“…Fortunately, cross-species translational studies offer a new opportunity for understanding this biosignal. Multiple groups have developed rodent analogues of the RewP (58)(59)(60)(61). This translational RewP analogue offers a chance to mechanistically test the network-level systems underlying separable reward domains.…”