D2/D3 dopamine supports the precision of mental state inferences and self-relevance of joint social outcomes.

Striatal dopamine is important in paranoid attributions, although its computational role in social inference remains elusive. We employed a simple game-theoretic paradigm and computational model of intentional attributions to investigate the effects of dopamine D2/D3 antagonism on ongoing mental state inference following social outcomes. Haloperidol, compared with the placebo, enhanced the impact of partner behaviour on beliefs about the harmful intent of partners, and increased learning from recent encounters. These alterations caused substantial changes to model covariation and negative correlations between self-interest and harmful intent attributions. Our findings suggest that haloperidol improves belief flexibility about others and simultaneously reduces the self-relevance of social observations. Our results may reflect the role of D2/D3 dopamine in supporting self-relevant mentalising. Our data and model bridge theory between general and social accounts of value representation. We demonstrate initial evidence for the sensitivity of our model and short social paradigm to drug intervention and clinical dimensions, allowing distinctions between mechanisms that operate across traits and states.

The computational psychiatry of reward: broken brains or misguided minds?

Research into the biological basis of emotional and motivational disorders is in danger of riding roughshod over a patient-centered psychiatry and falling into the dualist errors of the past, i.e., by treating mind and brain as conceptually distinct. We argue that a psychiatry informed by computational neuroscience, computational psychiatry, can obviate this danger. Through a focus on the reasoning processes by which humans attempt to maximize reward (and minimize punishment), and how such reasoning is expressed neurally, computational psychiatry can render obsolete the polarity between biological and psychosocial conceptions of illness. Here, the term 'psychological' comes to refer to information processing performed by biological agents, seen in light of underlying goals. We reflect on the implications of this perspective for a definition of mental disorder, including what is entailed in asserting that a particular disorder is 'biological' or 'psychological' in origin. We propose that a computational approach assists in understanding the topography of mental disorder, while cautioning that the point at which eccentric reasoning constitutes disorder often remains a matter of cultural judgment.

Reflection impulsivity and response inhibition in first-episode psychosis: relationship to cannabis use.

BACKGROUND: People with psychosis demonstrate impaired response inhibition on the Stop Signal Task (SST). It is less clear if this impairment extends to reflection impulsivity, a form of impulsivity that has been linked to substance use in non-psychotic samples. METHOD: We compared 49 patients with first-episode psychosis (FEP) and 30 healthy control participants on two forms of impulsivity measured using the Information Sampling Test (IST) and the SST, along with clinical and IQ assessments. We also compared those patients who used cannabis with those who had either given up or never used. RESULTS: Patients with FEP had significantly greater impairment in response inhibition but not in reflection impulsivity compared with healthy controls. By contrast, patients who reported current cannabis use demonstrated greater reflection impulsivity than those that had either given up or never used, whereas there were no differences in response inhibition. CONCLUSIONS: These data suggest that abnormal reflection impulsivity is associated with substance use in psychosis but not psychosis itself ; the opposite relationship may hold for response inhibition.

Characterisation of regional myocardial dynamics during mechanical alternans in heart of anaesthetised pig.

OBJECTIVE: The aim was to investigate the behaviour of regional myocardium during mechanical alternans in a multidirectional manner. METHODS: Mechanical alternans was induced in 12 anaesthetised open chested pigs by rapid atrial pacing. In contrast to previous studies, regional mechanical activity was simultaneously assessed at up to three different sites on the left ventricle using epicardial measuring devices able to provide multidirectional information on segment motion. Pressure-length loops were plotted to assess different patterns of segmental motion. The integral of pressure and length was calculated to obtain a regional work index for each beat. RESULTS: Pressure-length loops revealed profound abnormalities in segment motion and work index during regional mechanical alternans. Myocardial segments either performed alternate amounts of positive work on each beat or alternate amounts of positive and negative work on each beat. Alternating segments contracted out of phase with each other and were occasionally stretched during systole. CONCLUSIONS: The spatio-temporal heterogeneity of regional mechanical behaviour is greatly increased during mechanical alternans.