Decision-making (in)flexibility in gambling disorder

Background: Behavioral flexibility –the ability to dynamically readjust our behavior in response to reward contingency changes– is often investigated using probabilistic reversal learning tasks (PRLT). Poor PRLT performance has been proposed as a proxy for compulsivity, and theorized to be related to perseverative gambling. Previous attempts to measure inflexibility with the PRLT in patients with gambling disorder have, however, used a variety of indices that may conflate inflexibility with more general aspects of performance in the task. Methods: Trial-by-trial PRLT acquisition and reacquisition curves in 84 treatment-seeking patients with gambling disorder and 64 controls (non-gamblers and non-problem recreational gamblers) were analyzed to distinguish between (a) variability in acquisition learning, and (b) reacquisition learning in reversed contingency phases. Complementarily, stay/switch responses throughout the task were analyzed to identify (c) premature switching, and (d) sensitivity to accumulated negative feedback. Results and interpretation: Even after controlling for differences in acquisition learning, patients were slower to readjust their behavior in reversed contingency phases, and were more prone to maintain their decisions despite accumulated negative feedback. Inflexibility in patients with gambling disorder is thus a robust phenomenon that could predate gambling escalation, or result from massive exposure to gambling activities.This work was supported by grants from the Spanish Government (PSI2017-85488-P: Ministerio de Economía y Competitividad, Secretaría de Estado de Investigación, Desarrollo e Innovación, Convocatoria 2017 de Proyectos I+ D de Excelencia, Spain, co-funded by the Fondo Europeo de Desarrollo Regional, FEDER, European Commission; and PSI2013-45055: Ministerio de Economía y Competitividad, Secretaría de Estado de Invetigación, Desarrollo e Innovación, Convocatoria 2013 de Proyectos I+ D de Excelencia). Additionally, JFN was supported by a grant from the Spanish Government (PSI2017-85159-P. Ministerio de Ciencia, Innovación y Universidades). Funding agencies had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication

Goal-directed and habitual decision making under stress in Gambling Disorder: an fMRI study

The development of addictive behaviors has been suggested to be related to a transition from goal-directed to habitual decision making. Stress is a factor known to prompt habitual behavior and to increase the risk for addiction and relapse. In the current study, we therefore used functional MRI to investigate the balance between goal-directed ‘model-based’ and habitual ‘model-free’ control systems and whether acute stress would differentially shift this balance in gambling disorder (GD) patients compared to healthy controls (HCs). Using a within-subject design, 22 patients with GD and 20 HCs underwent stress induction or a control condition before performing a multistep decision-making task during fMRI. Salivary cortisol levels showed that the stress induction was successful. Contrary to our hypothesis, GD patients showed intact goal-directed decision making, which remained similar to HCs after stress induction. Bayes factors provided substantial evidence against a difference between the groups or a group-by-stress interaction on the balance between model-based and model-free decision making. Similarly, neural estimates did not differ between groups and conditions. These results challenge the notion that GD is related to an increased reliance on habitual (or decreased goal-directed) control, even during stress

A Prospectively Validated Prognostic Model for Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck Based on Radiomics of Computed Tomography Images

Background: Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) patients have high relapse and mortality rates. Imaging-based decision support may improve out-comes by optimising personalised treatment, and support patient risk stratification. We propose a multifactorial prognostic model including radiomics features to improve risk stratification for advanced HNSCC, compared to TNM eighth edition, the gold standard. Patient and methods: Data of 666 retrospective-and 143 prospective-stage III-IVA/B HNSCC patients were collected. A multivar-iable Cox proportional-hazards model was trained to predict overall survival (OS) using diagnostic CT-based radiomics features extracted from the primary tumour. Separate analyses were performed using TNM8, tumour volume, clinical and biological variables, and combinations thereof with radi-omics features. Patient risk stratification in three groups was assessed through Kaplan–Meier (KM) curves. A log-rank test was performed for significance (p-value < 0.05). The prognostic accuracy was reported through the concordance index (CI). Results: A model combining an 11-feature radiomics signature, clinical and biological variables, TNM8, and volume could significantly stratify the validation cohort into three risk groups (p < 0∙01, CI of 0.79 as validation). Conclusion: A combination of radiomics features with other predictors can predict OS very accurately for advanced HNSCC patients and improves on the current gold standard of TNM8

Altered orbitofrontal sulcogyral patterns in gambling disorder: a multicenter study

Gambling disorder is a serious psychiatric condition characterized by decision-making and reward processing impairments that are associated with dysfunctional brain activity in the orbitofrontal cortex (OFC). However, it remains unclear whether OFC functional abnormalities in gambling disorder are accompanied by structural abnormalities. We addressed this question by examining the organization of sulci and gyri in the OFC. This organization is in place very early and stable across life, such that OFC sulcogyral patterns (classified into Types I, II, and III) can be regarded as potential pre-morbid markers of pathological conditions. We gathered structural brain data from nine existing studies, reaching a total of 165 individuals with gambling disorder and 159 healthy controls. Our results, supported by both frequentist and Bayesian statistics, show that the distribution of OFC sulcogyral patterns is skewed in individuals with gambling disorder, with an increased prevalence of Type II pattern compared with healthy controls. Examination of gambling severity did not reveal any significant relationship between OFC sulcogyral patterns and disease severity. Altogether, our results provide evidence for a skewed distribution of OFC sulcogyral patterns in gambling disorder and suggest that pattern Type II might represent a pre-morbid structural brain marker of the disease. It will be important to investigate more closely the functional implications of these structural abnormalities in future work

Low anti-staphylococcal IgG responses in granulomatosis with polyangiitis patients despite long-term Staphylococcus aureus exposure

Chronic nasal carriage of the bacterium Staphylococcus aureus in patients with the autoimmune disease granulomatosis with polyangiitis (GPA) is a risk factor for disease relapse. To date, it was neither known whether GPA patients show similar humoral immune responses to S. aureus as healthy carriers, nor whether specific S. aureus types are associated with GPA. Therefore, this study was aimed at assessing humoral immune responses of GPA patients against S. aureus antigens in relation to the genetic diversity of their nasal S. aureus isolates. A retrospective cohort study was conducted, including 85 GPA patients and 18 healthy controls (HC). Humoral immune responses against S. aureus were investigated by determining serum IgG levels against 59 S. aureus antigens. Unexpectedly, patient sera contained lower anti-staphylococcal IgG levels than sera from HC, regardless of the patients' treatment, while total IgG levels were similar or higher. Furthermore, 210 S. aureus isolates obtained from GPA patients were characterized by different typing approaches. This showed that the S. aureus population of GPA patients is highly diverse and mirrors the general S. aureus population. Our combined findings imply that GPA patients are less capable of mounting a potentially protective antibody response to S. aureus than healthy individuals