Dopamine modulates default mode network deactivation in elderly individuals during the Tower of London task

doi:10.1016/j.neulet.2009.04.025

Neuroscience Letters

Volume 458, Issue 1, 10 July 2009, Pages 1-5

https://doi.org/10.1016/j.neulet.2009.04.025 Get rights and content

Abstract

Task-induced deactivation is frequently reported in the ventro-medial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), regions considered to belong to the default mode network. To investigate the effect of dopamine on task-induced deactivation, we used positron emission tomography to measure cerebral blood flow during performance of the Tower of London task before and after administration of the dopamine receptor agonist apomorphine in six healthy volunteers (49–66 years old) and six Parkinson disease patients (52–69 years old). Although task-induced deactivation was observed in the vmPFC and PCC in both groups and in both conditions, an inverse correlation between activation and problem complexity was observed in the vmPFC only in the apomorphine condition.

Section snippets

Acknowledgments

This work was supported by the Canadian Institutes for Health Research. The authors would like to thank Alexandra Soliman for her assistance.

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PD patients with poor response to levodopa showed less severe impairment of baseline motor symptoms, more severe dopaminergic deficits in the left inferior frontal, right posterior cingulate cortex and the right insula, and lower metabolism in the right supplementary motor area, right precuneus, right parietal cortex, right supramarginal gyrus, right postcentral gyrus, medulla, right rolandic operculum, right olfactory, the right insula and higher metabolism in the left cerebellum crus.
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Antipsychotic treatment has improved the disrupted functional connectivity (FC) and neurometabolites levels of the default mode network (DMN) in schizophrenia patients, but a direct relationship between FC change, neurometabolic level alteration, and symptom improvement has not been built. This study examined the association between the alterations in DMN FC, the changes of neurometabolites levels in the medial prefrontal cortex (MPFC), and the improvements in psychopathology in a longitudinal study of drug-naïve first-episode psychosis (FEP) patients.
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After treatment, the changes in γ-aminobutyric acid were correlated with the alterations of FC between the MPFC and DMN, while the changes in N-acetyl-aspartate were associated with the alterations of FC between the posterior cingulate cortex/precuneus and DMN. The FC changes of both regions were correlated with patients PANSS positive score reductions. The structural equation modeling analyses revealed that the changes of DMN FC mediated the relationship between the changes of neurometabolites and the symptom improvements of the patients.
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In the United States, the average duration of untreated psychosis (DUP) is 21 months, and it remains unknown how longer DUP may affect brain functioning in antipsychotic-naïve patients with first-episode psychosis. The objective was to determine the effects of DUP on functional connectivity and brain morphology measured with resting-state functional and structural magnetic resonance imaging.
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Parkinson's disease and changes in the appreciation of art: A comparison of aesthetic and formal evaluations of paintings between PD patients and healthy controls
2019, Brain and Cognition
Citation Excerpt :
Studies with PD patients on levodopa, both alone or in combination with DA agonists, also show failure of deactivation in the vmPFC while performing a sequence learning task (Argyelan et al., 2008), and in both the vmPFC and PCC during resting state (Tinaz, Lauro, Hallett, & Horovitz, 2016; however, see Delaveau et al., 2010). The PCC may also be a candidate for more direct changes brought about by PD pathology, for example increasing the resting receptivity to DA (see also Nagano-Saito, Liu, Doyon, & Dagher, 2009; Tomasi et al., 2009). This suggests intriguing future assessments, involving our response especially to art.
Parkinson’s disease (PD) is a progressing neurodegenerative disease predominantly involving the loss of dopamine producing neurons with hallmark symptoms of motor disorders and cognitive, motivational, emotional, and perceptual impairments. Intriguingly, PD can also be connected—often anecdotally—with a sudden burst of artistic creativity, motivation, or changed quality/style of produced art. This has led to growing empirical interest, promising a window into brain function and the unique neurological signature of artists. This topic also fits a growing interest from researchers in other areas, including Alzheimer’s or other dementia, which have suggested that specific changes in art production/appraisal may provide a unique basis for therapy, diagnosis, or understanding of these diseases. However, whether PD also shows similar impacts on how we perceive and evaluate art has never been systematically addressed. We compared a cohort of PD patients against age-matched healthy controls, asking participants to rate paintings using scales of liking and beauty and terms pertaining to artworks’ formal and conceptual qualities previously designed to provide a rubric for symptom identification. We found no evidence for PD-related differences in liking or beauty. However, PD patients showed higher ratings on assessed “emotionality,” potentially relating to the tie between PD, dopamine pathways, and emotion/reward.
Brain default-mode network dysfunction in addiction
2019, NeuroImage
Aberrant patterns of brain functional connectivity in the default mode network (DMN) have been observed across different classes of substance use disorder (SUD) and are associated with craving and relapse. In addicted individuals resting functional connectivity (RSFC) of the anterior DMN, which participates in attribution of personal value and emotional regulation, tends to be decreased, whereas RSFC of the posterior DMN, which directs attention to the internal world, tends to be increased. Aberrant RSFC within the DMN is believed to contribute to impaired self-awareness, negative emotions and to ruminations in addiction. Additionally, the disrupted connectivity between DMN and cortical regions involved with executive function, memory and emotion could be critical to drug-taking regardless of negative consequences and to stress-triggered relapse. At the system level, the dynamics of DMN interactions with the executive control and the salience networks are also disturbed in addiction. The DMN is prominently engaged during the withdrawal and preoccupation phases of the addiction cycle at the expense of the executive control network and with an enhanced participation of the salience network. In contrast, DMN prominence appears to be transitorily decreased during the intoxication phases. There is also growing evidence that disruption of the DMN in addiction reflects in part changes in dopaminergic, glutamatergic, and GABAergic signaling associated with acute and chronic drug use. Findings are starting to reveal DMN RSFC as a potential biomarker for predicting clinical outcomes in SUD and identify the DMN as a promising target for the treatment of addiction.
Levodopa imparts a normalizing effect on default-mode network connectivity in non-demented Parkinson's disease
2019, Neuroscience Letters
Citation Excerpt :
Previous studies also investigated the effect of dopamine/dopaminergic therapy on DMN [26,27]. However, although there were literatures that DMN is regulated by dopamine transmitters [10,26,27], there is still less evidence. Delaveau et al. [28] suggested that dopamine had a positive effect on the integrity of DMN, and that the deactivation of DMN in PD patients was the same as that of healthy subjects under the condition of administration of dopamine.
Parkinson’s disease (PD) is characterized with reduced dopamine level in the brain, resulting from the nigral degeneration. It is commonly accepted that the function of default mode network (DMN) is disturbed in PD, even in those who have no significant cognitive impairment. However, the relationship between the depletion of dopamine and DMN dysconnectivity is not fully clear. The aim of this study was to investigate the seed-based DMN connectivity and the influence of dopaminergic therapy on the DMN integrity in non-demented PD by using resting-state fMRI.
Resting-state fMRI data was collected from 24 non-demented PD patients before and after taking levodopa and 36 healthy controls (HCs). Functional connectivity (FC) was examined by a seed-based correlation approach.
Compared with HCs, decreased DMN connectivity in PD patients was observed, a number of which were significantly improved after taking levodopa therapy. Moreover, by directly comparing the DMN connectivity between ON- and OFF-medication conditions, we found significantly enhanced FC in a set of regions of DMN in the ON- medication condition. Conversely, we also found that the PCC revealed decreased FC with left inferior temporal.
DMN connectivity was found to be impaired in no-demented PD patients, and levodopa has the ability to impart a normalizing effect on DMN connectivity.

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Dopamine modulates default mode network deactivation in elderly individuals during the Tower of London task

Abstract

Section snippets

Acknowledgments

Neuroimage

Brain Cogn.

Brain Res. Bull.

Brain Res.

Neurobiol. Aging

Neurosci. Lett.

Neuroimage

Brain Res. Bull.

Neuroimage

Anatomoclinical and biochemical concepts of subcortical dementia

Conceptual processing during the conscious resting state. A functional MRI study

J. Cogn. Neurosci.

Apomorphine test for dopaminergic responsiveness: a dose assessment study

Mov. Disord.

Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space

J. Comput. Assist. Tomogr.

L-DOPA disrupts activity in the nucleus accumbens during reversal learning in Parkinson's disease

Neuropsychopharmacology

Dopaminergic modulation of high-level cognition in Parkinson's disease: the role of the prefrontal cortex revealed by PET

Brain

Mapping the network for planning: a correlational PET activation study with the Tower of London task

Brain

The role of the striatum and hippocampus in planning: a PET activation study in Parkinson's disease

Brain

D1 and D2 dopamine receptors in human substantia nigra: localization and the effect of aging

J. Neurochem.

The human brain is intrinsically organized into dynamic, anticorrelated functional networks

Proc. Natl. Acad. Sci. U S A