Hammes, Jochen, Theis, Hendrik, Giehl, Kathrin, Hoenig, Merle C., Greuel, Andrea, Tittgemeyer, Marc, Timmermann, Lars, Fink, Gereon R., Drzezga, Alexander ORCID: 0000-0001-6018-716X, Eggers, Carsten and van Eimeren, Thilo (2019). Dopamine metabolism of the nucleus accumbens and fronto-striatal connectivity modulate impulse control. Brain, 142. S. 733 - 744. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

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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 T-1-weighted images [mean age: 68 +/- 9.9 years, 67% male (patients)]. In 59 participants, F-18-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 cortexa 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hammes, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Theis, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giehl, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoenig, Merle C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greuel, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tittgemeyer, MarcUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Timmermann, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fink, Gereon R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drzezga, AlexanderUNSPECIFIEDorcid.org/0000-0001-6018-716XUNSPECIFIED
Eggers, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Eimeren, ThiloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-154337
DOI: 10.1093/brain/awz007
Journal or Publication Title: Brain
Volume: 142
Page Range: S. 733 - 744
Date: 2019
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2156
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ANTERIOR CINGULATE CORTEX; PARKINSONS-DISEASE; CONTROL DISORDERS; COMPULSIVE DISORDERS; RATING-SCALE; SPM TEMPLATE; RELEASE; STANDARDIZATION; QUESTIONNAIRE; NEUROSCIENCEMultiple languages
Clinical Neurology; NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15433

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