Muscarinic receptors mediate motivation via preparatory neural activity in humans.

Autor:	Grogan JP; Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.; Trinity College Institute of Neuroscience and Department of Psychology, Trinity College Dublin, Dublin, Ireland., Raemaekers M; Department of Experimental, Clinical and Health Psychology, Ghent University, Ghent, Belgium., van Swieten MMH; Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom., Green AL; Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom., Gillies MJ; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom., Manohar SG; Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Nov 20; Vol. 13. Date of Electronic Publication: 2024 Nov 20.
DOI:	10.7554/eLife.98922
Abstrakt:	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 electroencephalography (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 motivational 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, although THP reduced the incentive effect. 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. 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 impairs motivated action in healthy people, and that medial frontal preparatory neural activity mediates this for RT. Competing Interests: JG, MR, Mv, AG, MG, SM No competing interests declared (© 2024, Grogan et al.)
Databáze:	MEDLINE
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