RT Journal Article
SR Electronic
T1 Muscarinic receptors mediate motivation via preparatory neural activity in humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.07.28.454154
DO 10.1101/2021.07.28.454154
A1 John P. Grogan
A1 Matthias Raemaekers
A1 Maaike M. H. Van Swieten
A1 Alexander L. Green
A1 Martin J. Gillies
A1 Sanjay G. Manohar
YR 2021
UL http://biorxiv.org/content/early/2021/07/29/2021.07.28.454154.abstract
AB Motivation depends on dopamine, but might be modulated by acetylcholine which influences dopamine release in the striatum, and amplifies motivation in animal studies. A corresponding effect in humans would be important clinically, since anticholinergic drugs are frequently used in Parkinson’s disease, a condition that can also disrupt motivation. Reward and dopamine make us more ready to respond, as indexed by reaction times (RT), and move faster, sometimes termed vigour. These effects may be controlled by preparatory processes that can be tracked using EEG. We measured vigour in a placebo-controlled, double-blinded study of trihexyphenidyl (THP), a muscarinic antagonist, with an incentivised eye movement task and EEG. Participants responded faster and with greater vigour when incentives were high, but THP blunted these motivation effects, suggesting that muscarinic receptors facilitate invigoration by reward. Preparatory EEG build-up (contingent negative variation; CNV) was strengthened by high incentives and by muscarinic blockade. The amplitude of preparatory activity predicted both vigour and RT, although over distinct scalp regions. Frontal activity predicted vigour, whereas a larger, earlier, central component predicted RT. Indeed the incentivisation of RT was partly mediated by the CNV, though vigour was not. Moreover, the CNV mediated the drug’s effect on dampening incentives, suggesting that muscarinic receptors underlie the motivational influence on this preparatory activity. Taken together, these findings show that a muscarinic blocker used to treat Parkinson’s disease impairs motivated action in healthy people, and that medial frontal preparatory neural activity mediates this for RT.Competing Interest StatementThe authors have declared no competing interest.