Acute stress alters probabilistic reversal learning in healthy male adults.

Behavioural adaptation is a fundamental cognitive ability, ensuring survival by allowing for flexible adjustment to changing environments. In laboratory settings, behavioural adaptation can be measured with reversal learning paradigms requiring agents to adjust reward learning to stimulus-action-outcome contingency changes. Stress is found to alter flexibility of reward learning, but effect directionality is mixed across studies. Here, we used model-based functional MRI (fMRI) in a within-subjects design to investigate the effect of acute psychosocial stress on flexible behavioural adaptation. Healthy male volunteers (n = 28) did a reversal learning task during fMRI in two sessions, once after the Trier Social Stress Test (TSST), a validated psychosocial stress induction method, and once after a control condition. Stress effects on choice behaviour were investigated using multilevel generalized linear models and computational models describing different learning processes that potentially generated the data. Computational models were fitted using a hierarchical Bayesian approach, and model-derived reward prediction errors (RPE) were used as fMRI regressors. We found that acute psychosocial stress slightly increased correct response rates. Model comparison revealed that double-update learning with altered choice temperature under stress best explained the observed behaviour. In the brain, model-derived RPEs were correlated with BOLD signals in striatum and ventromedial prefrontal cortex (vmPFC). Striatal RPE signals for win trials were stronger during stress compared with the control condition. Our study suggests that acute psychosocial stress could enhance reversal learning and RPE brain responses in healthy male participants and provides a starting point to explore these effects further in a more diverse population.

Anodal tDCS over the medial prefrontal cortex enhances behavioral adaptation after punishments during reversal learning through increased updating of unchosen choice options.

The medial prefrontal cortex (mPFC) is thought to be central for flexible behavioral adaptation. However, the causal relationship between mPFC activity and this behavior is incompletely understood. We investigated whether transcranial direct current stimulation (tDCS) over the mPFC alters flexible behavioral adaptation during reward-based decision-making, targeting Montreal Neurological Institute (MNI) coordinates X = -8, Y = 62, Z = 12, which has previously been associated with impaired behavioral adaptation in alcohol-dependent patients. Healthy human participants (n = 61) received either anodal (n = 30) or cathodal (n = 31) tDCS versus sham tDCS while performing a reversal learning task. To assess the mechanisms of reinforcement learning (RL) underlying our behavioral observations, we applied computational models that varied with respect to the updating of the unchosen choice option. We observed that anodal stimulation over the mPFC induced increased choice switching after punishments compared with sham stimulation, whereas cathodal stimulation showed no effect on participants' behavior compared with sham stimulation. RL revealed increased updating of the unchosen choice option under anodal as compared with sham stimulation, which accounted well for the increased tendency to switch after punishments. Our findings provide a potential model for tDCS interventions in conditions related to flexible behavioral adaptation, such as addiction.

Urachal Carcinoma of the Bladder: Impact of Clinical and Immunohistochemical Parameters on Prognosis.

PURPOSE: Urachal carcinoma of the bladder is a rare malignancy. Its histological phenotype is similar to that of primary bladder and colorectal adenocarcinoma. The aim of this study was to explore the expression and prognostic relevance of 6 select protein markers of urachal carcinoma of the bladder, including p53, Ki67, RHAMM, BGN, IMP3 and MMP-7, which were formerly shown to be prognostic in urothelial carcinoma and colorectal adenocarcinoma. MATERIALS AND METHODS: Clinical and followup data were obtained on a total of 26 patients with urachal carcinoma of the bladder treated at 2 university hospitals. Immunohistochemical analysis of p53, Ki67, RHAMM, BGN, IMP3 and MMP-7 expression was performed in samples from 15 patients. Clinicopathological parameters and immunohistochemical results were tested for prognostic value on univariable and multivariable analyses. RESULTS: Followup was 50 months. Five-year overall and progression-free survival was 46% and 32%, respectively. On multivariable analysis a positive resection margin was an independent predictor of poor overall survival (p = 0.025). RHAMM (p = 0.0431), IMP3 (p = 0.0052), Ki67 (p = 0.0006) and p53 (p = 0.0024) expression rates were significantly increased in urachal carcinoma of the bladder cells compared to normal urothelium. IMP3 was elevated in Sheldon tumor stage IIIA compared to IIIB or greater (p = 0.0048). None of the analyzed protein markers was associated with survival. CONCLUSIONS: The independent prognostic value of a positive resection margin underlines the importance of complete surgical removal of urachal carcinoma of the bladder combined with en bloc resection of the median umbilical ligament and umbilicus. Our results in a limited number of samples show that Ki67, p53, RHAMM and IMP3 expression is enhanced but has no prognostic significance in urachal carcinoma of the bladder.