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Cited by 14Functional Brain Connectivity StudiesParkinson's Disease Mechanisms and TreatmentsNeurological disorders and treatments

Atomoxetine and citalopram alter brain network organization in Parkinson’s disease

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Borchert, Robin J, Rittman, Timothy, Rae, Charlotte L, Passamonti, Luca, Jones, Simon P, Vatansever, Deniz, Vázquez Rodríguez, Patricia, Ye, Zheng +4 more·2019·Brain Communications
DOI 10.1093/braincomms/fcz013PMC PMC6924537
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Abstract

Parkinson’s disease has multiple detrimental effects on motor and cognitive systems in the brain. In contrast to motor deficits, cognitive impairments in Parkinson’s disease are usually not ameliorated, and can even be worsened, by dopaminergic treatments. Recent evidence has shown potential benefits from restoring other neurotransmitter deficits, including noradrenergic and serotonergic transmission. Here, we study global and regional brain network organization using task-free imaging (also known as resting-state), which minimizes performance confounds and the bias towards predetermined networks. Thirty-three patients with idiopathic Parkinson’s disease were studied three times in a double-blinded, placebo-controlled counter-balanced crossover design, following placebo, 40 mg oral atomoxetine (selective noradrenaline reuptake inhibitor) or 30 mg oral citalopram (selective serotonin reuptake inhibitor). Neuropsychological assessments were performed outside the scanner. Seventy-six controls were scanned without medication to provide normative data for comparison to the patient cohort. Graph theoretical analysis of task-free brain connectivity, with a random 500-node parcellation, was used to measure the effect of disease in placebo-treated state (versus unmedicated controls) and pharmacological intervention (drug versus placebo). Relative to controls, patients on placebo had executive impairments (reduced fluency and inhibitory control), which was reflected in dysfunctional network dynamics in terms of reduced clustering coefficient, hub degree and hub centrality. In patients, atomoxetine improved fluency in proportion to plasma concentration (P = 0.006, r2 = 0.24), and improved response inhibition in proportion to increased hub Eigen centrality (P = 0.044, r2 = 0.14). Citalopram did not improve fluency or inhibitory control, but its influence on network integration and efficiency depended on disease severity: clustering (P = 0.01, r2 = 0.22), modularity (P = 0.043, r2 = 0.14) and path length (P = 0.006, r2 = 0.25) increased in patients with milder forms of Parkinson’s disease, but decreased in patients with more advanced disease (Unified Parkinson’s Disease Rating Scale motor subscale part III > 30). This study supports the use of task-free imaging of brain networks in translational pharmacology of neurodegenerative disorders. We propose that hub connectivity contributes to cognitive performance in Parkinson’s disease, and that noradrenergic treatment strategies can partially restore the neural systems supporting executive function.

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  • Nonstimulants have downstream effects that modulate activation patterns of frontoparietal regions through extracellular catecholamine and indirect effects that regulate brain connectivity patterns of the central executive network and default mode network.

    “Besides, they also have downstream effects that modulate the activation patterns of frontoparietal regions through extracellular catecholamine and indirect effects that regulate the brain connectivity patterns of the central executive network and default mode network (Borchert et al., 2019; Farr et al., 2014; Lin & Gau, 2015; Schulz et al., 2012; Shafritz et al., 2004).”

    From Overlapping and differential neuropharmacological mechanisms of stimulants and nonstimulants for attention-deficit/hyperactivity disorder: A comparative neuroimaging analysis (2024) · cites this paper as Borchert et al., 2019

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Authors
Borchert, R. J., Rittman, T., Rae, C. L., Passamonti, L., Jones, S. P., Vatansever, D., Vázquez Rodríguez, P., Ye, Z., Nombela, C., Hughes, L. E., Robbins, T. W., & Rowe, J. B.
Affiliations
  • University of Cambridge (GB)
  • University of Sussex (GB)
  • Fudan University (CN)
  • Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
  • Chinese Academy of Sciences (CN)
  • Hospital Clínico San Carlos (ES)
  • MRC Cognition and Brain Sciences Unit (GB)
Corresponding author
Rowe, James B
ORCID
Venue
Brain Communications
Publisher
Oxford University Press (OUP)
Published
2019-01-01
Volume
1
Issue
1
Pages
fcz013-fcz013
ISSN
2632-1297 (ISSN-L)
DOI
10.1093/braincomms/fcz013
PMC
PMC6924537
OpenAlex
W2971531144
Cited by
14
References
5
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 4 · 2021: 3 · 2020: 2 · 2019: 1
FWCI
0.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
  • Wellcome Trust (103838)
  • Parkinson’s UK
  • National Institute for Health Research’s Cambridge Biomedical Research Centre and the Medical Research Council (SUAG/004 R91365 RG62761)
  • James F McDonnell Foundation
  • Behavioural and Clinical Neuroscience Institute
  • Wellcome Trust and Medical Research Council
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords
Parkinson's disease, atomoxetine, citalopram, resting-state brain connectivity, graph theory, network hubs, executive function, fluency, response inhibition, disease severity, cognitive impairment, pharmacological interventions, network modularity, network efficiency, translational pharmacology, neuropsychological assessment, plasma drug concentration

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