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 unknown at what stage in the pathogenesis of 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 earliest stages of psychosis. We studied patients with first-episode psychosis (FEP) and help-seeking individuals at-risk for psychosis due to sub-threshold 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). FEP patients 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 FEP patients have abnormal meso-cortical signalling of reward-prediction errors, whereas 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

Reduction in Cerebral Perfusion after Heroin Administration: A Resting State Arterial Spin Labeling Study

Heroin dependence is a chronic relapsing brain disorder, characterized by the compulsion to seek and use heroin. Heroin itself has a strong potential to produce subjective experiences characterized by intense euphoria, relaxation and release from craving. The neurofunctional foundations of these perceived effects are not well known. In this study, we have used pharmacological magnetic resonance imaging (phMRI) in 15 heroin-dependent patients from a stable heroin-assisted treatment program to observe the steady state effects of heroin (60 min after administration). Patients were scanned in a cross-over and placebo controlled design. They received an injection of their regular dose of heroin or saline (placebo) before or after the scan. As phMRI method, we used a pulsed arterial spin labeling (ASL) sequence based on a flow-sensitive alternating inversion recovery (FAIR) spin labeling scheme combined with a single-shot 3D GRASE (gradient-spin echo) readout on a 3 Tesla scanner. Analysis was performed with Statistical Parametric Mapping (SPM 8), using a general linear model for whole brain comparison between the heroin and placebo conditions. We found that compared to placebo, heroin was associated with reduced perfusion in the left anterior cingulate cortex (ACC), the left medial prefrontal cortex (mPFC) and in the insula (both hemispheres). Analysis of extracted perfusion values indicate strong effect sizes and no gender related differences. Reduced perfusion in these brain areas may indicate self- and emotional regulation effects of heroin in maintenance treatment