Neural correlates of weighted reward prediction error during reinforcement learning classify response to cognitive behavioral therapy in depression

While cognitive behavioral therapy (CBT) is an effective treatment for major depressive disorder, only up to 45% of depressed patients will respond to it. At present, there is no clinically viable neuroimaging predictor of CBT response. Notably, the lack of a mechanistic understanding of treatment response has hindered identification of predictive biomarkers. To obtain mechanistically meaningful fMRI predictors of CBT response, we capitalize on pretreatment neural activity encoding a weighted reward prediction error (RPE), which is implicated in the acquisition and processing of feedback information during probabilistic learning. Using a conventional mass-univariate fMRI analysis, we demonstrate that, at the group level, responders exhibit greater pretreatment neural activity encoding a weighted RPE in the right striatum and right amygdala. Crucially, using multivariate methods, we show that this activity offers significant out-of-sample classification of treatment response. Our findings support the feasibility and validity of neurocomputational approaches to treatment prediction in psychiatry

Risk of transition to schizophrenia following first admission with substance-induced psychotic disorder: a population-based longitudinal cohort study

The potential for drugs of abuse to induce acute psychotic symptoms is well recognised. However, the likelihood of transition from initial substance-induced psychotic disorder (SIPD) to chronic psychosis is much less well understood. This study investigated the rate of SIPD transition to schizophrenia (F20), the time to conversion and other possible related factors. Using data from the Scottish Morbidity Record, we examined all patients (n = 3486) since their first admission to psychiatric hospital with a diagnosis of SIPD [International Classification of Diseases, Tenth Revision (ICD-10) codes F10-F19, with third digit five] from January 1997 to July 2012. Patients were followed until first episode of schizophrenia (ICD-10 code F20, with any third digit) or July 2012. Any change in diagnosis was noted in the follow-up period, which ranged from 1 day to 15.5 years across the groups. The 15.5-year cumulative hazard rate was 17.3% (s.e. = 0.007) for a diagnosis of schizophrenia. Cannabis, stimulant, opiate and multiple drug-induced psychotic disorder were all associated with similar hazard rates. The mean time to transition to a diagnosis of schizophrenia was around 13 years, although over 50% did so within 2 years and over 80% of cases presented within 5 years of SIPD diagnosis. Risk factors included male gender, younger age and longer first admission. SIPD episodes requiring hospital admission for more than 2 weeks are more likely to be associated with later diagnosis of schizophrenia. Follow-up periods of more than 2 years are needed to detect the majority of those individuals who will ultimately develop schizophrenia

Mild exogenous inflammation blunts neural signatures of bounded evidence accumulation and reward prediction error processing in healthy male participants

Background: Altered neural haemodynamic activity during decision making and learning has been linked to the effects of inflammation on mood and motivated behaviours. So far, it has been reported that blunted mesolimbic dopamine reward signals are associated with inflammation-induced anhedonia and apathy. Nonetheless, it is still unclear whether inflammation impacts neural activity underpinning decision dynamics. The process of decision making involves integration of noisy evidence from the environment until a critical threshold of evidence is reached. There is growing empirical evidence that such process, which is usually referred to as bounded accumulation of decision evidence, is affected in the context of mental illness. Methods: In a randomised, placebo-controlled, crossover study, 19 healthy male participants were allocated to placebo and typhoid vaccination. Three to four hours post-injection, participants performed a probabilistic reversal-learning task during functional magnetic resonance imaging. To capture the hidden neurocognitive operations underpinning decision-making, we devised a hybrid sequential sampling and reinforcement learning computational model. We conducted whole brain analyses informed by the modelling results to investigate the effects of inflammation on the efficiency of decision dynamics and reward learning. Results: We found that during the decision phase of the task, typhoid vaccination attenuated neural signatures of bounded evidence accumulation in the dorsomedial prefrontal cortex, only for decisions requiring short integration time. Consistent with prior work, we showed that, in the outcome phase, mild acute inflammation blunted the reward prediction error in the bilateral ventral striatum and amygdala. Conclusions: Our study extends current insights into the effects of inflammation on the neural mechanisms of decision making and shows that exogenous inflammation alters neural activity indexing efficiency of evidence integration, as a function of choice discriminability. Moreover, we replicate previous findings that inflammation blunts striatal reward prediction error signals

Perceptual learning alters post-sensory processing in human decision making

An emerging view in perceptual learning is that improvements in perceptual sensitivity are not only due to enhancements in early sensory representations but also due to changes in post-sensory decision-processing. In humans, however, direct neurobiological evidence of the latter remains scarce. Here, we trained participants on a visual categorization task over three days and used multivariate pattern analysis of the electroencephalogram to identify two temporally specific components encoding sensory (‘Early’) and decision (‘Late’) evidence, respectively. Importantly, the single-trial amplitudes of the Late, but not the Early component, were amplified in the course of training, and these enhancements predicted the behavioural improvements on the task. Correspondingly, we modelled these improvements with a reinforcement learning mechanism, using a reward prediction error signal to strengthen the readout of sensory evidence used for the decision. We validated this mechanism through a robust association between the model’s decision variables and the amplitudes of our Late component that encode decision evidence

Neighbourhood-level deprivation and morphological changes within the limbic stress circuit: results from a prospective, population-based, cohort study

Background Socioeconomic deprivation has been associated with chronic stress and poor mental health. In this study we investigated whether neighbourhood-level deprivation is associated with volumetric differences in a group of limbic forebrain structures—the hippocampus, amygdala, and ventromedial prefrontal cortex—which are implicated in the top-down modulation of the stress response. In addition we examined the role of circulating inflammatory markers in mediating the above associations.<p></p> Methods Participants were recruited as part of a larger prospective population-based cohort study. Each participant attended for two visits over 2·5 years between December, 2005, and May, 2008. Selection of participants was based on the Scottish Index of Multiple Deprivation 2004 and sampling was stratified to achieve a roughly equal distribution of the 666 participants across male and female participants and age groups within the most and least deprived areas of Glasgow, UK. Of 327 male participants, 140 consented to structural neuroimaging, and 42 middle-aged (mean 51 years, SD 8·7) neurologically healthy adults (21 from least deprived and 21 from most deprived areas) were randomly selected. Biomarkers of interest included cortisol, high-sensitivity C-reactive protein, intercellular adhesion molecule 1, fibrinogen, D-dimer, and interleukin 6. On the basis of the averaged Z scores of the biomarkers, we calculated an inflammatory index that we used as mediator variable.<p></p> Findings In multivariate analysis (repeated measures ANCOVA), neighbourhood deprivation predicted volumes of the regions of interest (F(1,37)=10·33, p=0·003, η2p=0·22). At the univariate level, neighbourhood deprivation was associated with smaller volumes in the right hippocampus (t=3·252, p=0·002, η2p=0·222) and right ventromedial/orbitofrontal cortex (t=2·275, p=0·029, η2p=0·12), but not in the left hippocampus, left ventromedial/orbitofrontal cortex, left and right amygdala, and left and right perigenual and subgenual anterior cingulate. The inflammatory index mediated the association between neighbourhood deprivation and volume of the right ventromedial/orbitofrontal cortex (β=−247·67, SE 134·86, 95% CI −582·76 to −32·99). No mediation effect by the inflammatory index was found in the association between neighbourhood deprivation and the right hippocampus.<p></p> Interpretation The finding of an association between smaller right hippocampus and neighbourhood deprivation is consistent with previous reports. To the best of our knowledge, ours is the first human study to report an association between neighbourhood deprivation and smaller volume in the right ventromedial/orbitofrontal cortex. Taking into account animal and human data, we speculate that the observed right-lateralised morphological changes in the hippocampus and ventromedial/orbitofrontal cortex could be due to an asymmetrical distribution of stress biomediators in the brain. It is also tempting to speculate that the observed structural abnormalities in the above regions might provide a neurobiological account of some of the cognitive and behavioural deficits that have been linked to lower socioeconomic status. Finally, aberrant activation of inflammatory pathways provides a potential mechanistic link between neighbourhood deprivation and structural remodelling of the brain.<p></p&gt

Functional MRI signatures of Pavlovian and instrumental valuation systems during a modified orthogonalized go/no-go task

Motivational (i.e. Pavlovian) values interfere with instrumental responding and can lead to suboptimal decision-making. In humans, task-based neuroimaging studies have only recently started illuminating the functional neuroanatomy of Pavlovian biasing of instrumental control. To provide a mechanistic understanding of the neural dynamics underlying the Pavlovian and instrumental valuation systems, analysis of neuroimaging data has been informed by computational modelling of conditioned behaviour. Nonetheless, due to collinearities in Pavlovian and instrumental predictions, previous research failed to tease out haemodynamic activity that is parametrically and dynamically modulated by coexistent Pavlovian and instrumental value expectations. Moreover, neural correlates of Pavlovian to instrumental transfer effects have so far only been identified in extinction (i.e. in the absence of learning). In this study we devised a modified version of the orthogonalized go/no-go paradigm which introduced Pavlovian only catch trials to better disambiguate trial-by-trial Pavlovian and instrumental predictions in both sexes. We found that haemodynamic activity in the ventromedial prefrontal cortex covaried uniquely with the model-derived Pavlovian value expectations. Notably, modulation of neural activity encoding for instrumental predictions in the supplementary motor cortex was linked to successful action selection in conflict conditions. Furthermore, haemodynamic activity in regions pertaining to the limbic system and medial prefrontal cortex was correlated with synergistic Pavlovian and instrumental predictions and improved conditioned behaviour during congruent trials. Altogether, our results provide incremental insights into the functional neuroanatomy of decision-making and corroborate the validity of our variant of the orthogonalized go/no-go task as a behavioural assay of the Pavlovian and instrumental valuation systems

Computerised cognitive training during early-stage psychosis improves cognitive deficits and gamma-band oscillations: a pilot study

No abstract available