Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Hammes, Jochen UNSPECIFIED UNSPECIFIED UNSPECIFIED Theis, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Giehl, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoenig, Merle C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Greuel, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Tittgemeyer, Marc UNSPECIFIED UNSPECIFIED UNSPECIFIED Timmermann, Lars UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gereon R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Drzezga, Alexander UNSPECIFIED orcid.org/0000-0001-6018-716X UNSPECIFIED Eggers, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED van Eimeren, Thilo UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language ANTERIOR CINGULATE CORTEX; PARKINSONS-DISEASE; CONTROL DISORDERS; COMPULSIVE DISORDERS; RATING-SCALE; SPM TEMPLATE; RELEASE; STANDARDIZATION; QUESTIONNAIRE; NEUROSCIENCE Multiple languages Clinical Neurology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15433