Universität zu Köln

Kayser, Andrew S., Vega, Taylor, Weinstein, Dawn, Peters, Jan ORCID: 0000-0002-0195-5357 and Mitchell, Jennifer M. (2017). Right inferior frontal cortex activity correlates with tolcapone responsivity in problem and pathological gamblers. NeuroImage-Clin., 13. S. 339 - 349. OXFORD: ELSEVIER SCI LTD. ISSN 2213-1582

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Abstract

Failures of self-regulation in problem and pathological gambling (PPG) are thought to emerge from failures of top-down control, reflected neurophysiologically in a reduced capacity of prefrontal cortex to influence activity within subcortical structures. In patientswith addictions, these impairments have been argued to alter evaluation of reward within dopaminergic neuromodulatory systems. Previously we demonstrated that augmenting dopamine tone in frontal cortex via use of tolcapone, an inhibitor of the dopamine-degrading enzyme catechol-Omethyltransferase (COMT), reduced delay discounting, ameasure of impulsivity, in healthy subjects. To evaluate this potentially translational approach to augmenting prefrontal inhibitory control, here we hypothesized that increasing cortical dopamine tone would reduce delay discounting in PPG subjects in proportion to its ability to augment top-down control. To causally test this hypothesis, we administered the COMT inhibitor tolcapone in a randomized, double-blind, placebo-controlled, within-subject study of 17 PPG subjects who performed a delay discounting task while functional MRI images were obtained. In this subject population, we found that greater BOLD activity during the placebo condition within the right inferior frontal cortex (RIFC), a region thought to be important for inhibitory control, correlated with greater declines in impulsivity on tolcapone versus placebo. Intriguingly, connectivity between RIFC and the right striatum, and not the level of activity within RIFC itself, increased on tolcapone versus placebo. Together, these findings support the hypothesis that tolcapone-mediated increases in top-down control may reduce impulsivity in PPG subjects, a finding with potential translational relevance for gambling disorders, and for behavioral addictions in general. Published by Elsevier Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kayser, Andrew S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vega, Taylor UNSPECIFIED UNSPECIFIED UNSPECIFIED Weinstein, Dawn UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Jan UNSPECIFIED orcid.org/0000-0002-0195-5357 UNSPECIFIED Mitchell, Jennifer M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-246384
DOI:	10.1016/j.nicl.2016.12.022
Journal or Publication Title:	NeuroImage-Clin.
Volume:	13
Page Range:	S. 339 - 349
Date:	2017
Publisher:	ELSEVIER SCI LTD
Place of Publication:	OXFORD
ISSN:	2213-1582
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BARRATT IMPULSIVENESS SCALE; INTERTEMPORAL CHOICE; FRONTOSTRIATAL ACTIVITY; DECISION-MAKING; SELF-CONTROL; DOPAMINE; BRAIN; DELAY; INHIBITION; ADDICTION Multiple languages Neuroimaging Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24638