Biology subjects

Robbins, T. W.

Publications and source records attributed to Robbins, T. W..

3 recordsLinked to original sources

bioRxiv2018

Action-outcome knowledge dissociates from behavior in obsessive-compulsive disorder following contingency degradation

Goal-directed and habitual systems orchestrate action control. In disorders of compulsivity, their interplay seems disrupted and actions persist despite being inappropriate and without relationship to the overall goal. We manipulated action-outcome contingency to test whether actions are goal-directed or habitual in obsessive-compulsive disorder (OCD), the prototypical disorder of compulsivity, in which prominent theories have suggested that dysfunctional beliefs underlie the necessity for compulsive actions.\n\nOCD patients responded more than controls when an action was causally less related to obtaining an outcome, indicating excessive habitual responding. Patients showed intact explicit action-outcome knowledge but this was not translated normally into behavior; the relationship between causality judgment and responding was blunted. OCD patients actions were dissociated from explicit action-outcome knowledge, providing experimental support for the ego-dystonic nature of OCD and suggesting that habitual action is not sustained by dysfunctional belief.

neuroscience↗

bioRxiv2017

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

RationalePatients 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.\n\nObjectiveIn this study we investigate potential dopaminergic dysfunction during reward processing in the context of OCD.\n\nMethodsWe 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 0.5mg; a dopamine receptor antagonist, amisulpride 400mg, 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.\n\nResultsThere were no significant group, drug or interaction effects in number of correct choices; computational modeling suggested a marginally significant difference in learning rates between groups (p=0.089, partial 2=0.1). In the imaging results, there was a significant interaction of group by drug (p=0.013, partial 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 2=0.26, 1-{beta} 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.\n\nConclusionsOur 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.

neuroscience↗

bioRxiv2017

Abnormal reward prediction error signalling in antipsychotic naive individuals with first episode psychosis or clinical risk for psychosis

Ongoing research suggests preliminary, though not entirely consistent, evidence of neural abnormalities in signalling prediction errors in schizophrenia. Supporting theories suggest mechanistic links between the disruption of these processes and the generation of psychotic symptoms. However, it is not known at what stage in psychosis these impairments in prediction error signalling develop. One major confound in prior studies is the use of medicated patients with strongly varying disease durations. Our study aims to investigate the involvement of the meso-cortico-striatal circuitry during reward prediction error signalling in the earliest stages of psychosis. We studied patients with first episode psychosis (FEP) and help-seeking individuals at risk for psychosis due to subthreshold prodromal psychotic symptoms. Patients with either FEP (n = 14), or at-risk for developing psychosis (n= 30), and healthy volunteers (n = 39) performed a reinforcement learning task during fMRI scanning. ANOVA revealed significant (p<0.05 family-wise error corrected) prediction error signalling differences between groups in the dopaminergic midbrain and right middle frontal gyrus (dorsolateral prefrontal cortex, DLPFC). Patients with FEP showed disrupted reward prediction error signalling compared to controls in both regions. At-risk patients showed intermediate activation in the midbrain that significantly differed from controls and from FEP patients, but DLPFC activation that did not differ from controls. Our study confirms that patients with FEP have abnormal meso-cortical signalling of reward prediction errors, whilst reward prediction error dysfunction in the at-risk patients appears to show a more nuanced pattern of activation with a degree of midbrain impairment but preserved cortical function.

neuroscience↗