Format

Send to

Choose Destination
Brain. 2019 Mar 1;142(3):733-743. doi: 10.1093/brain/awz007.

Dopamine metabolism of the nucleus accumbens and fronto-striatal connectivity modulate impulse control.

Author information

1
Multimodal Neuroimaging Group, Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany.
2
Department of Neurology, University Hospital of Marburg, Germany.
3
Max Planck Institute for Metabolism Research, Cologne, Germany.
4
Cologne Cluster of Excellence in Cellular Stress and Aging-Associated Disease (CECAD), University of Cologne, Germany.
5
Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany.
6
Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Germany.
7
German Center for Neurodegenerative Diseases (DZNE), Germany.

Abstract

Impulsive-compulsive behaviours like pathological gambling or hypersexuality are a frequent side effect of dopamine replacement therapy in patients with Parkinson's disease. Multiple imaging studies suggest a significant reduction of presynaptic dopamine transporters in the nucleus accumbens to be a predisposing factor, reflecting either a reduction of mesolimbic projections or, alternatively, a lower presynaptic dopamine transporter expression per se. Here, we aimed to test the hypothesis of fewer mesolimbic projections as a risk factor by using dopamine synthesis capacity as a proxy of dopaminergic terminal density. Furthermore, previous studies have demonstrated a reduction of fronto-striatal connectivity to be associated with increased risk of impulsive-compulsive behaviour in Parkinson's disease. Therefore, another aim of this study was to investigate the relationship between severity of impulsive-compulsive behaviour, dopamine synthesis capacity and fronto-striatal connectivity. Eighty participants underwent resting state functional MRI and anatomical T1-weighted images [mean age: 68 ± 9.9 years, 67% male (patients)]. In 59 participants, 18F-DOPA-PET was obtained and voxel-wise Patlak slopes indicating dopamine synthesis capacity were calculated. All participants completed the QUIP-RS questionnaire, a well validated test to quantify severity of impulsive-compulsive behaviour in Parkinson's disease. A voxel-wise correlation analysis between dopamine synthesis capacity and QUIP-RS score was calculated for striatal regions. To investigate the relationship between symptom severity and functional connectivity, voxel-wise correlations were performed. A negative correlation was found between dopamine synthesis capacity and QUIP-RS score in the nucleus accumbens (r = -0.57, P = 0.001), a region functionally connected to the rostral anterior cingulate cortex. The connectivity strength was modulated by QUIP-RS, i.e. patients with more severe impulsive-compulsive behaviours had a weaker functional connectivity between rostral anterior cingulate cortex and the nucleus accumbens. In addition, cortical thickness and severity of impulsive-compulsive behaviour were positively correlated in the subgenual rostral anterior cingulate cortex. We found three factors to be associated with severity of impulsive-compulsive behaviour: (i) decreased dopamine synthesis capacity in the nucleus accumbens; (ii) decreased functional connectivity of the rostral anterior cingulate cortex with the nucleus accumbens; and (iii) increased cortical thickness of the subgenual rostral anterior cingulate cortex. Rather than a downregulation of dopamine transporters, a reduction of mesolimbic dopaminergic projections in conjunction with a dysfunctional rostral anterior cingulate cortex-a region known to play a key role in impulse control-could be the most crucial neurobiological risk factor for the development of impulsive-compulsive behaviours in patients with Parkinson's disease under dopamine replacement therapy.

KEYWORDS:

Parkinson’s disease; imaging; impulsivity and inhibition disorders

PMID:
30753324
DOI:
10.1093/brain/awz007

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center