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000860706 1001_ $$0P:(DE-HGF)0$$aHammes, Jochen$$b0
000860706 245__ $$aDopamine metabolism of the nucleus accumbens and fronto-striatal connectivity modulate impulse control
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000860706 520__ $$aImpulsive-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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000860706 7001_ $$0P:(DE-HGF)0$$aTheis, Hendrik$$b1
000860706 7001_ $$0P:(DE-HGF)0$$aGiehl, Kathrin$$b2
000860706 7001_ $$0P:(DE-HGF)0$$aHoenig, Merle C$$b3
000860706 7001_ $$0P:(DE-HGF)0$$aGreuel, Andrea$$b4
000860706 7001_ $$0P:(DE-HGF)0$$aTittgemeyer, Marc$$b5
000860706 7001_ $$0P:(DE-HGF)0$$aTimmermann, Lars$$b6
000860706 7001_ $$0P:(DE-Juel1)131720$$aFink, Gereon Rudolf$$b7$$ufzj
000860706 7001_ $$0P:(DE-Juel1)177611$$aDrzezga, Alexander$$b8$$ufzj
000860706 7001_ $$0P:(DE-HGF)0$$aEggers, Carsten$$b9
000860706 7001_ $$0P:(DE-Juel1)169110$$avan Eimeren, Thilo$$b10$$eCorresponding author$$ufzj
000860706 773__ $$0PERI:(DE-600)1474117-9$$a10.1093/brain/awz007$$n3$$p733-743$$tBrain$$v142$$x1460-2156$$y2019
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