RT Journal Article
SR Electronic
T1 Computational dissociation of dopaminergic and cholinergic effects on voluntary behavior and inhibitory control
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 645093
DO 10.1101/645093
A1 Eduardo A. Aponte
A1 Dario Schöbi
A1 Klaas E. Stephan
A1 Jakob Heinzle
YR 2019
UL http://biorxiv.org/content/early/2019/05/22/645093.abstract
AB Patients with schizophrenia make more errors than healthy subjects in the antisaccade task. In this paradigm, participants are required to inhibit a reflexive action (a saccade to a target) and to initiate a voluntary action (a saccade in the opposite direction). While the precise origin of this deficit is not clear, it has been connected to aberrant neuromodulation, specifically in relation to dopamine (DA) and acetylcholine (ACh).To study how DA and ACh affect inhibitory control and voluntary action generation, we investigated two compounds (levodopa 200mg/galantamine 8mg) in healthy volunteers (N=100) performing the antisaccade task. Using a computational model of (anti)saccade generation (SERIA), we found that levodopa had no significant impact on inhibitory control. By contrast, galantamine reduced inhibition control at high doses, and this effect was reversed at lower doses. In addition, galantamine reduced the latency of voluntary saccades, whereas levodopa had the opposite effect. Our results challenge the hypothesis that increased DA has deleterious effects on inhibitory control. Instead, our findings suggest that levodopa improves the accuracy of voluntary actions at the cost of higher reaction times, while galantamine reduced the latency of voluntary actions, but negatively impacted inhibitory control at high doses.Finally, using machine learning, we demonstrate that model-based estimates of dopaminergic and cholinergic effects on inhibition and voluntary action control allow for inferring which drug was administered to a given individual. This may provide a starting point for establishing practical computational assays for differentiating neuromodulatory abnormalities in heterogeneous diseases like schizophrenia.