In:
PLOS Computational Biology, Public Library of Science (PLoS), Vol. 18, No. 5 ( 2022-5-9), p. e1010079-
Abstract:
Apathy is a debilitating feature of many neuropsychiatric diseases, that is typically described as a reduction of goal-directed behaviour. Despite its prevalence and prognostic importance, the mechanisms underlying apathy remain controversial. Degeneration of the locus coeruleus-noradrenaline system is known to contribute to motivational deficits, including apathy. In healthy people, noradrenaline has been implicated in signalling the uncertainty of expectations about the environment. We proposed that noradrenergic deficits contribute to apathy by modulating the relative weighting of prior beliefs about action outcomes. We tested this hypothesis in the clinical context of Parkinson’s disease, given its associations with apathy and noradrenergic dysfunction. Participants with mild-to-moderate Parkinson’s disease ( N = 17) completed a randomised double-blind, placebo-controlled, crossover study with 40 mg of the noradrenaline reuptake inhibitor atomoxetine. Prior weighting was inferred from psychophysical analysis of performance in an effort-based visuomotor task, and was confirmed as negatively correlated with apathy. Locus coeruleus integrity was assessed in vivo using magnetisation transfer imaging at ultra-high field 7T. The effect of atomoxetine depended on locus coeruleus integrity: participants with a more degenerate locus coeruleus showed a greater increase in prior weighting on atomoxetine versus placebo. The results indicate a contribution of the noradrenergic system to apathy and potential benefit from noradrenergic treatment of people with Parkinson’s disease, subject to stratification according to locus coeruleus integrity. More broadly, these results reconcile emerging predictive processing accounts of the role of noradrenaline in goal-directed behaviour with the clinical symptom of apathy and its potential pharmacological treatment.
Type of Medium:
Online Resource
ISSN:
1553-7358
DOI:
10.1371/journal.pcbi.1010079
DOI:
10.1371/journal.pcbi.1010079.g001
DOI:
10.1371/journal.pcbi.1010079.g002
DOI:
10.1371/journal.pcbi.1010079.g003
DOI:
10.1371/journal.pcbi.1010079.g004
DOI:
10.1371/journal.pcbi.1010079.g005
DOI:
10.1371/journal.pcbi.1010079.t001
DOI:
10.1371/journal.pcbi.1010079.s001
DOI:
10.1371/journal.pcbi.1010079.s002
DOI:
10.1371/journal.pcbi.1010079.s003
DOI:
10.1371/journal.pcbi.1010079.s004
DOI:
10.1371/journal.pcbi.1010079.s005
DOI:
10.1371/journal.pcbi.1010079.s006
DOI:
10.1371/journal.pcbi.1010079.s007
DOI:
10.1371/journal.pcbi.1010079.s008
DOI:
10.1371/journal.pcbi.1010079.s009
DOI:
10.1371/journal.pcbi.1010079.s010
DOI:
10.1371/journal.pcbi.1010079.s011
DOI:
10.1371/journal.pcbi.1010079.s012
DOI:
10.1371/journal.pcbi.1010079.r001
DOI:
10.1371/journal.pcbi.1010079.r002
DOI:
10.1371/journal.pcbi.1010079.r003
DOI:
10.1371/journal.pcbi.1010079.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2193340-6
Bookmarklink