Dopamine metabolism of the nucleus accumbens and fronto-striatal connectivity modulate impulse control
| Autor: | Marc Tittgemeyer, Carsten Eggers, Hendrik Theis, Lars Timmermann, Gereon R. Fink, Merle C Hoenig, Kathrin Giehl, Jochen Hammes, Thilo van Eimeren, Andrea Greuel, Alexander Drzezga |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Parkinson's disease Dopamine Nucleus accumbens physiology [Impulsive Behavior] 03 medical and health sciences 0302 clinical medicine Risk Factors Connectome medicine Humans ddc:610 metabolism [Dopamine] physiopathology [Gyrus Cinguli] Anterior cingulate cortex Aged Dopamine transporter Dopamine Plasma Membrane Transport Proteins biology Resting state fMRI business.industry metabolism [Corpus Striatum] Dopaminergic metabolism [Nucleus Accumbens] Middle Aged medicine.disease Magnetic Resonance Imaging 030104 developmental biology medicine.anatomical_structure nervous system drug effects [Nucleus Accumbens] biology.protein SLC6A3 protein human Female physiology [Nerve Net] Hypersexuality physiopathology [Parkinson Disease] Neurology (clinical) medicine.symptom business Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Brain 142(3), 733-743 (2019). doi:10.1093/brain/awz007 |
| ISSN: | 1460-2156 0006-8950 |
| DOI: | 10.1093/brain/awz007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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