Bidirectional dopaminergic intervention reduces exaggerated cingulate prediction error signal in OCD
Mon-A7-Talk II-05
Presented by: Franziska Knolle
Patients with obsessive-compulsive disorder (OCD) show exaggerated error responses and prediction error learning signals, with data converging on the anterior cingulate cortex as a key locus of dysfunction. Considerable evidence has linked prediction error processing to dopaminergic function. We therefore investigated potential dopaminergic dysfunction during reward processing in OCD.
During a fMRI-task, OCD patients (n=18) and controls (n=18) learned probabilistic associations between abstract stimuli and monetary rewards. On separate visits, participants were administered a dopamine receptor agonist, pramipexole 0.5mg; a dopamine receptor antagonist, amisulpride 400mg; and a placebo, while completing the task. We fitted a Q-learning computational model to fMRI prediction error responses; with regions of interest in the anterior cingulate and nucleus accumbens.
There were no effects in the number of correct choices; but computational modelling suggested marginal difference in learning rates between groups. The imaging results revealed that OCD patients showed abnormally strong cingulate signalling of prediction errors during omission of an expected reward, with unexpected reduction by both pramipexole and amisulpride. Furthermore, exaggerated cingulate prediction error signalling to omitted reward in placebo was related to trait subjective difficulty in self-regulating behaviour in OCD.
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 cingulate activation.
During a fMRI-task, OCD patients (n=18) and controls (n=18) learned probabilistic associations between abstract stimuli and monetary rewards. On separate visits, participants were administered a dopamine receptor agonist, pramipexole 0.5mg; a dopamine receptor antagonist, amisulpride 400mg; and a placebo, while completing the task. We fitted a Q-learning computational model to fMRI prediction error responses; with regions of interest in the anterior cingulate and nucleus accumbens.
There were no effects in the number of correct choices; but computational modelling suggested marginal difference in learning rates between groups. The imaging results revealed that OCD patients showed abnormally strong cingulate signalling of prediction errors during omission of an expected reward, with unexpected reduction by both pramipexole and amisulpride. Furthermore, exaggerated cingulate prediction error signalling to omitted reward in placebo was related to trait subjective difficulty in self-regulating behaviour in OCD.
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 cingulate activation.
Keywords: Anterior cingulate, Computational model, Nucleus accumbens, Obsessive-compulsive disorder, Prediction error, Reward learning