Hauptseite > Publikationsdatenbank > Dopamine metabolism of the nucleus accumbens and fronto-striatal connectivity modulate impulse control > print |
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024 | 7 | _ | |a 10.1093/brain/awz007 |2 doi |
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100 | 1 | _ | |0 P:(DE-HGF)0 |a Hammes, Jochen |b 0 |
245 | _ | _ | |a Dopamine metabolism of the nucleus accumbens and fronto-striatal connectivity modulate impulse control |
260 | _ | _ | |a Oxford |b Oxford Univ. Press |c 2019 |
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520 | _ | _ | |a 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. |
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700 | 1 | _ | |0 P:(DE-HGF)0 |a Theis, Hendrik |b 1 |
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700 | 1 | _ | |0 P:(DE-HGF)0 |a Hoenig, Merle C |b 3 |
700 | 1 | _ | |0 P:(DE-HGF)0 |a Greuel, Andrea |b 4 |
700 | 1 | _ | |0 P:(DE-HGF)0 |a Tittgemeyer, Marc |b 5 |
700 | 1 | _ | |0 P:(DE-HGF)0 |a Timmermann, Lars |b 6 |
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700 | 1 | _ | |0 P:(DE-Juel1)169110 |a van Eimeren, Thilo |b 10 |e Corresponding author |u fzj |
773 | _ | _ | |0 PERI:(DE-600)1474117-9 |a 10.1093/brain/awz007 |n 3 |p 733-743 |t Brain |v 142 |x 1460-2156 |y 2019 |
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