Evidence map›Paper›PMID 40260733›Full record

Observational studyMovement disorders : official journal of the Movement Disorder Society2025

Molecular-Informed Network Analysis Unveils Fatigue-Related Functional Connectivity in Parkinson's Disease.

Ilaria Antonella Di Vico, Manuela Moretto, Agnese Tamanti, Giovanni Tomelleri, Giulia Burati, Daniel Martins, Ottavia Dipasquale, Mattia Veronese, Alessandra Bertoldo, Elisa Menini and 5 more

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Movement disorders : official journal of the Movement Disorder Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Ilaria Antonella Di VicoNeurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico Borgo Roma, University of Verona, Verona, Italy.
Manuela MorettoDepartment of Information Engineering, University of Padova, Padova, Italy.
Agnese TamantiNeurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico Borgo Roma, University of Verona, Verona, Italy.
Giovanni TomelleriNeurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico Borgo Roma, University of Verona, Verona, Italy.
Giulia BuratiNeurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico Borgo Roma, University of Verona, Verona, Italy.
Daniel MartinsInstitute of Psychiatry, Psychology & Neuroscience, Department of Neuroimaging, King's College London, Institute of Psychiatry, London, UK.
Ottavia DipasqualeInstitute of Psychiatry, Psychology & Neuroscience, Department of Neuroimaging, King's College London, Institute of Psychiatry, London, UK.
Mattia VeroneseDepartment of Information Engineering, University of Padova, Padova, Italy.
Alessandra BertoldoDepartment of Information Engineering, University of Padova, Padova, Italy.
Elisa MeniniNeurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico Borgo Roma, University of Verona, Verona, Italy.
Angela SandriNeurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico Borgo Roma, University of Verona, Verona, Italy.
Sarah OttavianiNeurology Unit, Policlinico Borgo Trento Verona, Verona, Italy.
Francesca Benedetta PizziniDepartment of Engineering for Innovation Medicine, University of Verona, Verona, Italy.
Michele TinazziNeurology Unit, Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico Borgo Roma, University of Verona, Verona, Italy.ORCID https://orcid.org/0000-0002-2370-7063
Marco CastellaroDepartment of Information Engineering, University of Padova, Padova, Italy.ORCID https://orcid.org/0000-0002-1203-2670

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFatigue in Parkinson's disease (PD) is a prevalent and debilitating non-motor symptom. Despite its significant impact on quality of life, the underlying neurochemical and network-based mechanisms remain poorly understood.

objectivesThis observational study applied a multimodal imaging approach to explore potential links between the functional connectivity of neurotransmitter-specific circuits and fatigue in a sample of patients with PD.

methodsWe acquired resting-state functional magnetic resonance imaging data in 35 patients with PD including 18 with clinically significant fatigue and 17 without. We applied the receptor-enriched analysis of functional connectivity by targets (REACT) pipeline to derive patients' specific molecularly enriched networks informed by the spatial distribution of the dopamine, noradrenaline, serotonin transporters, and metabotropic glutamate 5 receptors as assessed using molecular imaging data in independent samples of healthy controls. We then conducted whole-brain analyses inspecting both categorical differences between groups of patients with and without clinically significant fatigue, and associations exploring the full within-sample variation in symptom ratings.

resultsWe found a significant decrease in noradrenaline-enriched and glutamate-enriched functional connectivity in key regions, belonging to the sensorimotor, salience, and default mode network, with increasing fatigue severity. Notably, noradrenaline-enriched functional connectivity reductions were widespread, while glutamate-enriched functional connectivity reductions were more restricted to the supplementary motor area. No significant relationships between fatigue and dopamine or serotonin-enriched functional connectivity were found.

conclusionsThese findings offer supportive evidence for the putative involvement of the noradrenaline and glutamate systems in the genesis of fatigue in PD, opening new directions for treatment development exploring these neurochemical systems. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Indexed as

BrainConnectomeFatigueNerve NetParkinson DiseaseAgedFemaleHumansMagnetic Resonance ImagingMaleMiddle Agedfunctional connectivityneuroreceptor systemParkinson's diseaseresting state fatigue

Identifiers

PMID40260733
PMCPMC12371637

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.