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        Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder

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        Author
        Murray, Graham
        Knolle, Franziska
        Ersche, Karen D
        Craig, Kevin J
        Abbott, Sanja
        Shabbir, Shaila S
        Fineberg, Naomi
        Suckling, John
        Sahakian, Barbara J.
        Bullmore, Edward T.
        Robbins, Trevor W.
        Attention
        2299/21576
        Abstract
        Rationale: Patients with obsessive-compulsive disorder (OCD) have been found to show exaggerated error responses and prediction error learning signals in a variety of EEG and fMRI tasks, with data converging on the anterior cingulate cortex as a key locus of dysfunction. Considerable evidence has linked prediction error processing to dopaminergic function. Objective: In this study, we investigate potential dopaminergic dysfunction during reward processing in the context of OCD. Methods: We studied OCD patients (n = 18) and controls (n = 18) whilst they learned probabilistic associations between abstract stimuli and monetary rewards in the fMRI scanner involving administration (on separate visits) of a dopamine receptor agonist, pramipexole 0.5 mg; a dopamine receptor antagonist, amisulpride 400 mg; and placebo. We fitted a Q-learning computational model to fMRI prediction error responses; group differences were examined in anterior cingulate and nucleus accumbens regions of interest. Results: There were no significant group, drug, or interaction effects in the number of correct choices; computational modeling suggested a marginally significant difference in learning rates between groups (p = 0.089, partial ƞ 2 = 0.1). In the imaging results, there was a significant interaction of group by drug (p = 0.013, partial ƞ 2 = 0.13). OCD patients showed abnormally strong cingulate signaling of prediction errors during omission of an expected reward, with unexpected reduction by both pramipexole and amisulpride (p = 0.014, partial ƞ 2 = 0.26, 1-β error probability = 0.94). Exaggerated cingulate prediction error signaling to omitted reward in placebo was related to trait subjective difficulty in self-regulating behavior in OCD. Conclusions: Our data support cingulate dysfunction during reward processing in OCD, and bidirectional remediation by dopaminergic modulation, suggesting that exaggerated cingulate error signals in OCD may be of dopaminergic origin. The results help to illuminate the mechanisms through which dopamine receptor antagonists achieve therapeutic benefit in OCD. Further research is needed to disentangle the different functions of dopamine receptor agonists and antagonists during bidirectional modulation of cingulate activation.
        Publication date
        2019-08-01
        Published in
        Psychopharmacology
        Published version
        https://doi.org/10.1007/s00213-019-05292-2
        License
        http://creativecommons.org/licenses/by/4.0/
        Other links
        http://hdl.handle.net/2299/21576
        Relations
        School of Life and Medical Sciences
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